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Phytochemicals: Biosynthesis, Metabolism and Biological Activities

A topical collection in Molecules (ISSN 1420-3049). This collection belongs to the section "Natural Products Chemistry".

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Editor

Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, 20133 Milan, Italy
Interests: essential oils; bioactive phytochemicals; ethnopharmacology; antimicrobial resistance; one health; food security
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

In their environment, plants have to cope with a plethora of stressful conditions such as pathogenic microorganisms, phytophagy, competitor plants, environmental pollutants and adverse climatic changes which have exerted a selective pressure on plant species and populations. In addition, coevolution, based on plant-microbe, plant-herbivore and plant-environment interactions, has represented a further force that has shaped evolving plants. Therefore, these sessile organisms have evolved a complex machinery in order to counteract harmful conditions, based on a number of sequential barriers which include both preformed and inducible chemical defenses. In evolutionary and ecological terms, chemical diversity has determined the successful of plants in their environment: these organisms synthesize secondary metabolites, i.e., phytochemicals, not only to defend themselves from their enemies, but also to secure the reproductive process, with pigments coloring flowers and volatile compounds attracting pollinators.

Efficacy of phytochemicals as defense metabolites mostly depends on their multiple molecular targets, both in prokaryotic and eukaryotic cells, including receptors, ion channels, enzymes, structural macromolecules and nucleic acids. Consequently, secondary metabolites interfere with a number of cell processes such as cell cycle, mitosis, signaling pathways, protein synthesis and folding, programmed cell death, energy metabolism and so on. Not least because of this unique nature of phytochemicals, and because plant tissues contain hundreds of natural compounds, there exists a lower risk of developing phytochemical-resistant pathogens or insects compared with conventional agrochemicals or pharmaceuticals.

We invite investigators to submit both original research and review articles that explore all the aspects of plant secondary metabolism, with emphasis on functional roles of phytochemicals in plant organisms. We are also interested in contributions focusing on biological and pharmacological activities of secondary metabolites such as biocide, antioxidant, anti-inflammatory and anticancer activities, as well as on their roles in human nutrition as health-promoting agents.

Potential topics include, but are not limited to: stress metabolism; chemical ecology; plant stress physiology; plant defense mechanisms; xenobiotic metabolism; global climate changes; environmental pollution; medicinal and food plants; functional foods; nutraceuticals; essential oils

Prof. Dr. Marcello Iriti
Collection Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The article processing charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs).

Keywords

  • bioactive phytochemicals

  • natural products

  • botanicals

  • phytoalexins

  • secondary metabolites

  • melatonin

Published Papers (127 papers)

2023

Jump to: 2022, 2021, 2020, 2019, 2018, 2017, 2016, 2015, 2014

27 pages, 5023 KiB  
Review
A Review of Classification, Biosynthesis, Biological Activities and Potential Applications of Flavonoids
by Shen Chen, Xiaojing Wang, Yu Cheng, Hongsheng Gao and Xuehao Chen
Molecules 2023, 28(13), 4982; https://doi.org/10.3390/molecules28134982 - 25 Jun 2023
Cited by 12 | Viewed by 3804
Abstract
Flavonoids represent the main class of plant secondary metabolites and occur in the tissues and organs of various plant species. In plants, flavonoids are involved in many biological processes and in response to various environmental stresses. The consumption of flavonoids has been known [...] Read more.
Flavonoids represent the main class of plant secondary metabolites and occur in the tissues and organs of various plant species. In plants, flavonoids are involved in many biological processes and in response to various environmental stresses. The consumption of flavonoids has been known to reduce the risk of many chronic diseases due to their antioxidant and free radical scavenging properties. In the present review, we summarize the classification, distribution, biosynthesis pathways, and regulatory mechanisms of flavonoids. Moreover, we investigated their biological activities and discuss their applications in food processing and cosmetics, as well as their pharmaceutical and medical uses. Current trends in flavonoid research are also briefly described, including the mining of new functional genes and metabolites through omics research and the engineering of flavonoids using nanotechnology. This review provides a reference for basic and applied research on flavonoid compounds. Full article
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23 pages, 5504 KiB  
Article
Hydrogel for the Controlled Delivery of Bioactive Components from Extracts of Eupatorium glutinosum Lam. Leaves
by Lizbeth Zamora-Mendoza, Santiago Nelson Vispo, Lola De Lima, José R. Mora, António Machado and Frank Alexis
Molecules 2023, 28(4), 1591; https://doi.org/10.3390/molecules28041591 - 07 Feb 2023
Cited by 4 | Viewed by 1690
Abstract
This research reported a hydrogel loaded with the ethanolic and methanolic extracts of Eupatorium glutinosum Lam. The E. glutinosum extracts were characterized by phytochemical screening, Fourier-transform infrared spectroscopy (FTIR), thin-layer chromatography (TLC), and UV/Vis profile identification. This research also evaluated the pharmacological activity [...] Read more.
This research reported a hydrogel loaded with the ethanolic and methanolic extracts of Eupatorium glutinosum Lam. The E. glutinosum extracts were characterized by phytochemical screening, Fourier-transform infrared spectroscopy (FTIR), thin-layer chromatography (TLC), and UV/Vis profile identification. This research also evaluated the pharmacological activity of the extracts using antimicrobial, antioxidant, and anti-inflammatory assays prior to polymeric encapsulation. Results indicate that extracts inhibit the Escherichia colii DH5-α (Gram negative) growth; excellent antioxidant activity was evaluated by the ferric reducing power and total antioxidant activity assays, and extracts showed an anti-hemolytic effect. Moreover, the cotton and microcrystalline cellulose hydrogels demonstrate successful encapsulation based on characterization and kinetics studies such as FTIR, extract release, and swelling degree. Moreover, effective antibacterial activity was registered by the loaded hydrogel. The overall results encourage and show that Eupatorium glutinosum-loaded hydrogel may find a wide range of bandage and wound healing applications in the biomedical area. Full article
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2022

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33 pages, 2322 KiB  
Article
Targeted and Untargeted Metabolomic Analyses Reveal Organ Specificity of Specialized Metabolites in the Model Grass Brachypodium distachyon
by Anna Piasecka, Aneta Sawikowska, Nicolas Jedrzejczak-Rey, Mariola Piślewska-Bednarek and Paweł Bednarek
Molecules 2022, 27(18), 5956; https://doi.org/10.3390/molecules27185956 - 13 Sep 2022
Cited by 1 | Viewed by 1978
Abstract
Brachypodium distachyon, because of its fully sequenced genome, is frequently used as a model grass species. However, its metabolome, which constitutes an indispensable element of complex biological systems, remains poorly characterized. In this study, we conducted comprehensive, liquid chromatography-mass spectrometry (LC-MS)-based metabolomic [...] Read more.
Brachypodium distachyon, because of its fully sequenced genome, is frequently used as a model grass species. However, its metabolome, which constitutes an indispensable element of complex biological systems, remains poorly characterized. In this study, we conducted comprehensive, liquid chromatography-mass spectrometry (LC-MS)-based metabolomic examination of roots, leaves and spikes of Brachypodium Bd21 and Bd3-1 lines. Our pathway enrichment analysis emphasised the accumulation of specialized metabolites representing the flavonoid biosynthetic pathway in parallel with processes related to nucleotide, sugar and amino acid metabolism. Similarities in metabolite profiles between both lines were relatively high in roots and leaves while spikes showed higher metabolic variance within both accessions. In roots, differences between Bd21 and Bd3-1 lines were manifested primarily in diterpenoid metabolism, while differences within spikes and leaves concerned nucleotide metabolism and nitrogen management. Additionally, sulphate-containing metabolites differentiated Bd21 and Bd3-1 lines in spikes. Structural analysis based on MS fragmentation spectra enabled identification of 93 specialized metabolites. Among them phenylpropanoids and flavonoids derivatives were mainly determined. As compared with closely related barley and wheat species, metabolic profile of Brachypodium is characterized with presence of threonate derivatives of hydroxycinnamic acids. Full article
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11 pages, 13649 KiB  
Article
Identification and Functional Characterization of Tyrosine Decarboxylase from Rehmannia glutinosa
by Yuanjun Li, Yanan Wang, Longyu Huang, Chunrong Chen, Na An and Xiaoke Zheng
Molecules 2022, 27(5), 1634; https://doi.org/10.3390/molecules27051634 - 01 Mar 2022
Cited by 3 | Viewed by 1719
Abstract
Rehmannia glutinosa is an important medicinal plant that has long been used in Chinese traditional medicine. Acteoside, one of the bioactive components from R. glutinosa, possessed various pharmacological activities for human health; however, the molecular mechanism of acteoside formation is not fully [...] Read more.
Rehmannia glutinosa is an important medicinal plant that has long been used in Chinese traditional medicine. Acteoside, one of the bioactive components from R. glutinosa, possessed various pharmacological activities for human health; however, the molecular mechanism of acteoside formation is not fully understood. In the current study, a novel tyrosine decarboxylase (designated as RgTyDC2) was identified from the R. glutinosa transcriptome. Biochemical analysis of RgTyDC2 showed RgTyDC2 uses tyrosine and dopa as the substrate to produce tyramine and dopamine, respectively, and it displays higher catalytic efficiency toward tyrosine than dopa. Moreover, the transcript level of RgTyDC2 was consistent with the accumulation pattern of acteoside in R. glutinosa, supporting its possible role in the biosynthesis of acteoside in vivo. Full article
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2021

Jump to: 2023, 2022, 2020, 2019, 2018, 2017, 2016, 2015, 2014

15 pages, 2422 KiB  
Article
Optimization Method for Phenolic Compounds Extraction from Medicinal Plant (Juniperus procera) and Phytochemicals Screening
by Abdalrhaman M. Salih, Fahad Al-Qurainy, Mohammad Nadeem, Mohamed Tarroum, Salim Khan, Hassan O. Shaikhaldein, Abdulrahman Al-Hashimi, Alanoud Alfagham and Jawaher Alkahtani
Molecules 2021, 26(24), 7454; https://doi.org/10.3390/molecules26247454 - 09 Dec 2021
Cited by 21 | Viewed by 3332
Abstract
Juniperus procera is a natural source of bioactive compounds with the potential of antitumor, antimicrobial, insecticidal, antifungal, and antioxidant activities. An optimization method was developed for total phenolic content (TPC), total flavonoid content (TFC), and total tannin content (TTC) in leaf and seed [...] Read more.
Juniperus procera is a natural source of bioactive compounds with the potential of antitumor, antimicrobial, insecticidal, antifungal, and antioxidant activities. An optimization method was developed for total phenolic content (TPC), total flavonoid content (TFC), and total tannin content (TTC) in leaf and seed extract of Juniperus procera. Organic solvents (methanol (99.8%), ethanol (99%), and acetone (99.5%)), and deionized water (DI) were used for extraction. The estimation of TPC, TFC, and TTC in plant materials was carried out using UV-spectrophotometer and HPLC with the standards gallic acid, quercetin, and tannic acid. Recovery of TPC in leaf extract ranged from 2.9 to 9.7 mg GAE/g DW, TFC from 0.9 to 5.9 mg QE/g DW, and TTC ranged from 1.5 to 4.3 mg TA/g DW while the TPC value in the seed extract ranged from 0.53 to 2.6 mg GAE/g DW, TFC from 0.5 to 1.6 mg QE/g DW, and TTC ranged from 0.5 to 1.4 mg TA/g DW. This result revealed that methanol is the best solvent for recovery of the TPC value (9.7 mg) from leaf extract in comparison to other solvents. Ethanol recorded the highest result of TFC (5.9 mg) in leaf extract among the solvents whereas acetone was the best for TTC yield recovery from leaf extract (4.3 mg). In the case of the seed extract, ethanol was the best solvent for both TPC (2.6 mg), and TFC (1.6 mg) recovery in comparison to other solvents. Total tannin content in methanol resulted in significant recovery from seed extract (1.4 mg). Separation and quantification of gallic acid, quercetin, and tannic acid in plant materials were undertaken using HPLC. Gallic acid in leaf and seed of J. procera ranged from 6.6 to 9.2, 6.5 to 7.2 µg/g DW, quercetin from 6.3 to 18.2, 0.9 to 4.2 µg/g DW, and tannic acid from 16.2 to 29.3, 6.6 to 9.3 µg/g DW, respectively. Solvents have shown a significant effect in the extraction of phenolic compounds. Moreover, phytochemicals in plant materials were identified using GC-MS and resulted in very important bioactive compounds, which include anti-inflammatory, antibacterial, and antitumor agents such as ferruginol, phenanthrene, and n-hexadecanoic acid. In conclusion, the optimal solvent for extraction depends on the part of the plant material and the compounds that are to be isolated. Full article
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29 pages, 21120 KiB  
Review
Taxonomic Insights and Its Type Cyclization Correlation of Volatile Sesquiterpenes in Vitex Species and Potential Source Insecticidal Compounds: A Review
by Ighor C. Barreto, Anderson S. de Almeida and José G. Sena Filho
Molecules 2021, 26(21), 6405; https://doi.org/10.3390/molecules26216405 - 23 Oct 2021
Cited by 10 | Viewed by 2731
Abstract
Sesquiterpenes (SS) are secondary metabolites formed by the bonding of 3 isoprene (C5) units. They play an important role in the defense and signaling of plants to adapt to the environment, face stress, and communicate with the outside world, and their evolutionary history [...] Read more.
Sesquiterpenes (SS) are secondary metabolites formed by the bonding of 3 isoprene (C5) units. They play an important role in the defense and signaling of plants to adapt to the environment, face stress, and communicate with the outside world, and their evolutionary history is closely related to their physiological functions. This review considers their presence and extensively summarizes the 156 sesquiterpenes identified in Vitextaxa, emphasizing those with higher concentrations and frequency among species and correlating with the insecticidal activities and defensive responses reported in the literature. In addition, we classify the SS based on their chemical structures and addresses cyclization in biosynthetic origin. Most relevant sesquiterpenes of the Vitex genus are derived from the germacredienyl cation mainly via bicyclogermacrene and germacrene C, giving rise to aromadrendanes, a skeleton with the highest number of representative compounds in this genus, and 6,9-guaiadiene, respectively, indicating the production of 1.10-cyclizing sesquiterpene synthases. These enzymes can play an important role in the chemosystematics of the genus from their corresponding routes and cyclizations, constituting a new approach to chemotaxonomy. In conclusion, this review is a compilation of detailed information on the profile of sesquiterpene in the Vitex genus and, thus, points to new unexplored horizons for future research. Full article
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20 pages, 4693 KiB  
Article
Identification and Characterization of Glucosyltransferase That Forms 1-Galloyl-β-d-Glucogallin in Canarium album L., a Functional Fruit Rich in Hydrolysable Tannins
by Qinghua Ye, Shiyan Zhang, Nana Qiu, Linmin Liu, Wei Wang, Qian Xie, Qiang Chang and Qingxi Chen
Molecules 2021, 26(15), 4650; https://doi.org/10.3390/molecules26154650 - 31 Jul 2021
Cited by 8 | Viewed by 2349
Abstract
Hydrolysable tannins (HTs) are useful secondary metabolites that are responsible for pharmacological activities and astringent taste, flavor, and quality in fruits. They are also the main polyphenols in Canarium album L. (Chinese olive) fruit, an interesting and functional fruit that has been cultivated [...] Read more.
Hydrolysable tannins (HTs) are useful secondary metabolites that are responsible for pharmacological activities and astringent taste, flavor, and quality in fruits. They are also the main polyphenols in Canarium album L. (Chinese olive) fruit, an interesting and functional fruit that has been cultivated for over 2000 years. The HT content of C. album fruit was 2.3–13 times higher than that of berries with a higher content of HT. 1-galloyl-β-d-glucose (βG) is the first intermediate and the key metabolite in the HT biosynthesis pathway. It is catalyzed by UDP-glucosyltransferases (UGTs), which are responsible for the glycosylation of gallic acid (GA) to form βG. Here, we first reported 140 UGTs in C. album. Phylogenetic analysis clustered them into 14 phylogenetic groups (A, B, D–M, P, and Q), which are different from the 14 typical major groups (A~N) of Arabidopsis thaliana. Expression pattern and correlation analysis showed that UGT84A77 (Isoform0117852) was highly expressed and had a positive correlation with GA and βG content. Prokaryotic expression showed that UGT84A77 could catalyze GA to form βG. These results provide a theoretical basis on UGTs in C. album, which will be helpful for further functional research and availability on HTs and polyphenols. Full article
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13 pages, 7393 KiB  
Article
Effects of Abiotic Elicitors on Expression and Accumulation of Three Candidate Benzophenanthridine Alkaloids in Cultured Greater Celandine Cells
by Seyed Mohammad Hashemi, Mohammad Reza Naghavi, Esmaeil Bakhshandeh, Mehdi Ghorbani, Chanditha Priyanatha and Peiman Zandi
Molecules 2021, 26(5), 1395; https://doi.org/10.3390/molecules26051395 - 05 Mar 2021
Cited by 9 | Viewed by 2268 | Correction
Abstract
Efforts to develop the necessary biotechnologies in Greater Celandine (Chelidonium majus L.), a leading plant resource for the development of plant-derived medicines, have been hampered by the lack of knowledge about transcriptome and metabolome regulations of its medicinal components. Therefore, this study [...] Read more.
Efforts to develop the necessary biotechnologies in Greater Celandine (Chelidonium majus L.), a leading plant resource for the development of plant-derived medicines, have been hampered by the lack of knowledge about transcriptome and metabolome regulations of its medicinal components. Therefore, this study aimed to examine the effect of abiotic elicitors, methyl jasmonate (MJ) and salicylic acid (SA), at different time courses (12, 24, 48, and 72 h), on expression and metabolome of key benzophenanthridine alkaloids (BPAs) in an optimized in vitro culture. Gene expression analysis indicated the upregulation of CFS (cheilanthifoline synthase) to 2.62, 4.85, and 7.28 times higher than the control at 12, 24, and 48 h respectively, under MJ elicitation. Besides, MJ upregulated the expression of TNMT (tetrahydroprotoberberine N-methyltransferase) to 2.79, 4.75, and 7.21 times at 12, 24, and 48 h respectively, compared to the control. Investigation of BPAs revealed a significant enhancement in the chelidonine content (9.86 µg/mg) after 72 h of MJ elicitation. Additionally, sanguinarine content increased to its highest level (3.42 µg/mg) after 24 h of MJ elicitation; however, no significant enhancement was detected in its content in shorter elicitation time courses. Generally, higher gene expression and BPAs’ level was observed through longer elicitation courses (48 and 72 h). Our findings take part in improving the understanding of transcription and metabolic regulation of BPAs in cultured Greater Celandine cells. Full article
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13 pages, 3717 KiB  
Article
Ethanol Extract of Amomum tsao-ko Ameliorates Ovariectomy-Induced Trabecular Loss and Fat Accumulation
by Ki-Shuk Shim, Youn-Hwan Hwang, Seon-A Jang, Taesoo Kim and Hyunil Ha
Molecules 2021, 26(4), 784; https://doi.org/10.3390/molecules26040784 - 03 Feb 2021
Cited by 6 | Viewed by 2163
Abstract
In Asia, Amomum tsao-ko has long been used as a spice or seasoning in food to stimulate digestion. In the present study, we evaluated the effects of ethanol extract of Amomum tsao-ko (EEAT) on menopausal osteoporosis and obesity. After the administration of EEAT [...] Read more.
In Asia, Amomum tsao-ko has long been used as a spice or seasoning in food to stimulate digestion. In the present study, we evaluated the effects of ethanol extract of Amomum tsao-ko (EEAT) on menopausal osteoporosis and obesity. After the administration of EEAT in ovariectomy (OVX) mice models for five weeks, microcomputed tomography and a histological analysis were performed to assess, respectively, the trabecular structure and the fat accumulation in adipose, liver, and bone tissues. We also examined the effects of EEAT on a bone marrow macrophage model of osteoclastogenesis by in vitro stimulation from the receptor activator of nuclear factor-kappa Β ligand (RANKL) through real-time PCR and Western blot analysis. In addition, ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) with authentic standards was applied to characterize the phytochemical profiling of EEAT. We found that EEAT significantly decreased OVX-induced body weight gain and fat accumulation, significantly prevented OVX-induced deterioration of bone mineral density and microstructure of trabecular tissues, and significantly inhibited osteoclast differentiation by downregulating NF-κB/Fos/NFATc1 signaling in osteoclasts. Furthermore, UHPLC–MS/MS identified eight beneficial phytochemicals in EEAT. Collectively, these results suggest that EEAT might be an effective nutraceutical candidate to attenuate menopausal osteoporosis by inhibiting osteoclastogenesis and to prevent obesity by suppressing fat accumulation. Full article
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13 pages, 16524 KiB  
Article
Kahweol, a Diterpenoid Molecule, Inhibits CTGF-Dependent Synthetic Phenotype Switching and Migration in Vascular Smooth Muscle Cells
by Jeong Hee Lee, Seok Tae Choi and Young Jin Kang
Molecules 2021, 26(3), 640; https://doi.org/10.3390/molecules26030640 - 26 Jan 2021
Cited by 5 | Viewed by 2183
Abstract
Vascular smooth muscle cell (VSMC) phenotype switching from contractile to synthetic is essential for proliferation and migration in vascular pathophysiology. Connective tissue growth factor (CTGF) is a matricellular protein involved in cell adhesion, migration, and proliferation. Kahweol, a diterpene molecule in arabica coffee [...] Read more.
Vascular smooth muscle cell (VSMC) phenotype switching from contractile to synthetic is essential for proliferation and migration in vascular pathophysiology. Connective tissue growth factor (CTGF) is a matricellular protein involved in cell adhesion, migration, and proliferation. Kahweol, a diterpene molecule in arabica coffee beans, has been reported to have anti-inflammatory, antiproliferative, and apoptotic effects in many cells. However, in VSMCs, the effects of kahweol on CTGF activities have not been investigated. Thus, in this study, the effects and associated mechanisms of kahweol in CTGF-dependent phenotype switching and migration in VSMCs were examined. Experiments were performed on primary rat aortic smooth muscle cells and a rat VSMC line, A7r5. Western blot analysis was used to determine the protein levels. The mRNA levels of synthetic markers were measured by qRT-PCR. Migration of VSMCs was evaluated by wound healing and transwell assays. Kahweol reduced the angiotensin II (Ang II)-induced CTGF expression. Further, kahweol inhibited expressions of synthetic phenotype markers of VSMC. The kahweol-reduced synthetic marker protein levels were reversed by the administration of rCTGF. However, expressions of contractile phenotype markers of VSMC were not affected. Kahweol suppressed Ang II-stimulated VSMC migration. Moreover, kahweol downregulated Ang II-induced p-FAK, p-Erk, and Yes-associated protein (YAP) protein expressions. Taken together, in Ang II-stimulated VSMCs, kahweol inhibited CTGF-dependent synthetic phenotype switching and migration, with focal adhesion kinase (FAK), Erk, and YAP involved in the underlying mechanisms of the kahweol effects. These results suggest that kahweol has a potential as a therapeutic agent to inhibit CTGF, which is a molecular target in sclerogenic vascular disease. Full article
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2020

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14 pages, 4389 KiB  
Article
LC-MS/MS-Based Profiling of Tryptophan-Related Metabolites in Healthy Plant Foods
by Sara Vitalini, Michele Dei Cas, Federico Maria Rubino, Ileana Vigentini, Roberto Foschino, Marcello Iriti and Rita Paroni
Molecules 2020, 25(2), 311; https://doi.org/10.3390/molecules25020311 - 13 Jan 2020
Cited by 19 | Viewed by 5555
Abstract
Food plants contain hundreds of bioactive phytochemicals arising from different secondary metabolic pathways. Among these, the metabolic route of the amino acid Tryptophan yields a large number of plant natural products with chemically and pharmacologically diverse properties. We propose the identifier “indolome” to [...] Read more.
Food plants contain hundreds of bioactive phytochemicals arising from different secondary metabolic pathways. Among these, the metabolic route of the amino acid Tryptophan yields a large number of plant natural products with chemically and pharmacologically diverse properties. We propose the identifier “indolome” to collect all metabolites in the Tryptophan pathway. In addition, Tryptophan-rich plant sources can be used as substrates for the fermentation by yeast strains to produce pharmacologically active metabolites, such as Melatonin. To pursue this technological development, we have developed a UHPLC-MS/MS method to monitor 14 Tryptophan, Tryptamine, amino-benzoic, and pyridine metabolites. In addition, different extraction procedures to improve the recovery of Tryptophan and its derivatives from the vegetal matrix were tested. We investigated soybeans, pumpkin seeds, sesame seeds, and spirulina because of their botanical diversity and documented healthy effects. Four different extractions with different solvents and temperatures were tested, and water extraction at room temperature was chosen as the most suitable procedure to extract the whole Tryptophan metabolites pattern (called by us “indolome”) in terms of ease, high efficiency, short time, low cost, and sustainability. In all plant matrices, Tryptophan was the most abundant indole compound, while the pattern of its metabolites was different in the diverse plants extracts. Overall, 5-OH Tryptamine and Kynurenine were the most abundant compounds, despite being 100–1000-fold lower than Tryptophan. Melatonin was undetected in all extracts, but sesame showed the presence of a Melatonin isomer. The results of this study highlight the variability in the occurrence of indole compounds among diverse food plants. The knowledge of Tryptophan metabolism in plants represents a relevant issue for human health and nutrition. Full article
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2019

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15 pages, 3005 KiB  
Article
Accession-Level Differentiation of Urushiol Levels, and Identification of Cardanols in Nascent Emerged Poison Ivy Seedlings
by Aneirin A. Lott, Emily R. Baklajian, Christopher C. Dickinson, Eva Collakova and John G. Jelesko
Molecules 2019, 24(23), 4213; https://doi.org/10.3390/molecules24234213 - 20 Nov 2019
Cited by 3 | Viewed by 3047
Abstract
Poison ivy (Toxicodendron radicans (L.) Kuntze) shows accession-level differentiation in a variety of morphometric traits, suggesting local adaptation. To investigate whether the presumed defense compound urushiol also demonstrates accession-level accumulation differences, in vitro nascent germinated poison ivy seedlings from geographically isolated populations [...] Read more.
Poison ivy (Toxicodendron radicans (L.) Kuntze) shows accession-level differentiation in a variety of morphometric traits, suggesting local adaptation. To investigate whether the presumed defense compound urushiol also demonstrates accession-level accumulation differences, in vitro nascent germinated poison ivy seedlings from geographically isolated populations were germinated in vitro and then assayed for known urushiol congener accumulation levels. Significant accession-level differences in the accumulation levels of total C15- and C17-, total C15-, total C17-, specific C15 congeners, and specific C17 congeners of urushiol were identified. In addition, hereto novel C15- and C17-urushiol isomers were identified as well. Cardanols are assumed to be the penultimate metabolites giving rise to urushiols, but this assumption was not previously empirically validated. C15-cardanol congeners and isomers corresponding to expected substrates needed to produce the observed C15-urushiol congeners and isomers were identified in the same poison ivy seedling extracts. Total C15-cardanol and C15-cardanol congeners also showed significant accession-level differences. Based on the observed C15-cardanol congeners in poison ivy, the penultimate step in urushiol biosynthesis was proposed to be a cardanol-specific hydroxylase activity. Full article
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18 pages, 2443 KiB  
Article
Cell Suspensions of Cannabis sativa (var. Futura): Effect of Elicitation on Metabolite Content and Antioxidant Activity
by Damiano Gabotti, Franca Locatelli, Erica Cusano, Elena Baldoni, Annamaria Genga, Laura Pucci, Roberto Consonni and Monica Mattana
Molecules 2019, 24(22), 4056; https://doi.org/10.3390/molecules24224056 - 09 Nov 2019
Cited by 22 | Viewed by 4522
Abstract
Cannabis sativa L. is one of the most-studied species for its phytochemistry due to the abundance of secondary metabolites, including cannabinoids, terpenes and phenolic compounds. In the last decade, fiber-type hemp varieties have received interest for the production of many specialized secondary metabolites [...] Read more.
Cannabis sativa L. is one of the most-studied species for its phytochemistry due to the abundance of secondary metabolites, including cannabinoids, terpenes and phenolic compounds. In the last decade, fiber-type hemp varieties have received interest for the production of many specialized secondary metabolites derived from the phenylpropanoid pathway. The interest in these molecules is due to their antioxidant activity. Since secondary metabolite synthesis occurs at a very low level in plants, the aim of this study was to develop a strategy to increase the production of such compounds and to elucidate the biochemical pathways involved. Therefore, cell suspensions of industrial hemp (C. sativa L. var. Futura) were produced, and an advantageous elicitation strategy (methyl jasmonate, MeJA) in combination with precursor feeding (tyrosine, Tyr) was developed. The activity and expression of phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT) increased upon treatment. Through 1H-NMR analyses, some aromatic compounds were identified, including, for the first time, 4-hydroxyphenylpyruvate (4-HPP) in addition to tyrosol. The 4-day MeJA+Tyr elicited samples showed a 51% increase in the in vitro assay (2,2-diphenyl-1-picrylhydrazyl, DPPH) radical scavenging activity relative to the control and a 80% increase in the cellular antioxidant activity estimated on an ex vivo model of human erythrocytes. Our results outline the active metabolic pathways and the antioxidant properties of hemp cell extracts under the effect of specific elicitors. Full article
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2018

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14 pages, 1575 KiB  
Article
Investigation of the In Vivo Metabolism of Sibirioside A and Angoroside C in Rats by HPLC-ESI-IT-TOF-MSn
by Yi-Fan Zhang, Li-Jia Liu, Feng Xu, Ming-Ying Shang, Guang-Xue Liu and Shao-Qing Cai
Molecules 2018, 23(10), 2702; https://doi.org/10.3390/molecules23102702 - 19 Oct 2018
Cited by 9 | Viewed by 3428
Abstract
Sibirioside A and angoroside C are two important phenylpropanoid glycosides of the traditional Chinese medicine Scrophulariae Radix. High performance liquid chromatography, coupled with an ion trap time-of-flight multistage mass spectrometry equipped with electrospray ionization source (HPLC-ESI-IT-TOF-MSn), was applied to the profile [...] Read more.
Sibirioside A and angoroside C are two important phenylpropanoid glycosides of the traditional Chinese medicine Scrophulariae Radix. High performance liquid chromatography, coupled with an ion trap time-of-flight multistage mass spectrometry equipped with electrospray ionization source (HPLC-ESI-IT-TOF-MSn), was applied to the profile and we identified the metabolites of sibirioside A and angoroside C in vivo in rats. A total of four metabolites of sibirioside A were identified: SM1, SM2 and SM3 which were known as new compounds. A total of 25 metabolites were detected for angoroside C: AM4, AM5, AM6, AM7, AM16, AM17, AM20, AM21, AM22, AM23 and AM25 which were identified to be new compounds. The main metabolic reactions were hydrolysis, reduction, hydroxylation, methylation, sulfation, and gluconylation. The prototype of sibirioside A was widely distributed in tissues found in the heart, liver, spleen, lung, kidney, stomach and small intestine of rats, and mainly distributed in the stomach, small intestine, kidney and liver. But for angoroside C, nothing was found in the viscera except the stomach and small intestine. The metabolites of sibirioside A were mainly eliminated from feces, while it was urine for the metabolites of angoroside C. Furthermore, 19 metabolites were likely to have bioactivities based on the ‘PharmMapper’ analysis, which roughly matched the known pharmacological activities of Scrophulariae Radix (SR) and the prototypes. One of the main pharmacological activities of SR in traditional Chinese medicine is anti-diabetes, and the predicted results showed that SM1, SM2, SM3, AM2, AM4, AM5, AM6, AM9, AM10, AM11, AM12, AM13, AM15, AM18, AM19, AM24, and AM25 might be used to cure diabetes. These findings provide a reference for studying the metabolism, distribution and pharmacological actions of phenylpropanoid glycosides in vivo. Full article
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10 pages, 1173 KiB  
Article
Effect of Red Wine Intake on Serum and Salivary Melatonin Levels: A Randomized, Placebo-Controlled Clinical Trial
by Elena M. Varoni, Rita Paroni, Jacopo Antognetti, Giovanni Lodi, Andrea Sardella, Antonio Carrassi and Marcello Iriti
Molecules 2018, 23(10), 2474; https://doi.org/10.3390/molecules23102474 - 27 Sep 2018
Cited by 5 | Viewed by 3513
Abstract
Melatonin (MLT) is a recently discovered phytochemical in wine, but its influence on physiological MLT levels is still unknown. This study aimed at evaluating variations, in serum and saliva, of MLT concentrations after the intake of MLT-enriched red wine. Twelve healthy volunteers were [...] Read more.
Melatonin (MLT) is a recently discovered phytochemical in wine, but its influence on physiological MLT levels is still unknown. This study aimed at evaluating variations, in serum and saliva, of MLT concentrations after the intake of MLT-enriched red wine. Twelve healthy volunteers were recruited to receive 125 mL of red wine naturally lacking of MLT (placebo, PLC), or the same wine enriched with MLT (MLT+). A physiological steady decline of serum MLT was observed from baseline up to 90 min, for both wines. After PLC intake, the decrease was significantly faster than the one occurring after MLT+ wine, which thus delayed the drop down of serum MLT with a plateau at 30–60 min. Salivary MLT levels slightly peaked at 45 min after MLT+ wine intake, without statistical significance. Therefore, the intake of a glass of MLT-enriched red wine changed serum levels of the indoleamine, supporting the role of wine MLT in counteracting the physiological decline of the hormone into the bloodstream. Full article
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11 pages, 1073 KiB  
Article
Carbon (δ13C) and Nitrogen (δ15N) Stable Isotope Composition Provide New Insights into Phenotypic Plasticity in Broad Leaf Weed Rumex acetosa under Allelochemical Stress
by M. Iftikhar Hussain, Manuel J. Reigosa and Adele Muscolo
Molecules 2018, 23(10), 2449; https://doi.org/10.3390/molecules23102449 - 25 Sep 2018
Cited by 5 | Viewed by 3750
Abstract
Phenolic compounds, hydroquinone and cinnamic acid derivatives have been identified as major allelochemicals with known phytotoxicity from allelopathic plant Acacia melanoxylon R. Br. Several phenolic compounds such as ferulic acid (FA), p-hydroxybenzoic acid (pHBA) and flavonoid (rutin, quercetin) constituents occur in the [...] Read more.
Phenolic compounds, hydroquinone and cinnamic acid derivatives have been identified as major allelochemicals with known phytotoxicity from allelopathic plant Acacia melanoxylon R. Br. Several phenolic compounds such as ferulic acid (FA), p-hydroxybenzoic acid (pHBA) and flavonoid (rutin, quercetin) constituents occur in the phyllodes and flowers of A. melanoxylon and have demonstrated inhibitory effects on germination and physiological characteristics of lettuce and perennial grasses. However, to date, little is known about the mechanisms of action of these secondary metabolites in broad-leaved weeds at ecophysiological level. The objective of this study was to determine the response of Rumex acetosa carbon isotope composition and other physiological parameters to the interaction of plant secondary metabolites (PSM) (FA and pHBA) stress and the usefulness of carbon isotope discrimination (Δ13C) as indicative of the functional performance of intrinsic water use efficiency (iWUE) at level of plant leaf. R. acetosa plant were grown under greenhouse condition and subjected to PSM stress (0, 0.1, 0.5, 1.0, and 1.5 mM) for six days. Here, we show that FA and pHBA are potent inhibitors of Δ13C that varied from 21.0‰ to 22.9‰. Higher pHBA and FA supply enhanced/retard the Nleaf and increased the Cleaf while ratio of intercellular CO2 concentration from leaf to air (Ci/Ca) was significantly decreased as compared to control. Leaf water content and leaf osmotic potential were decreased following treatment with both PSM. The Ci/Ca decreased rapidly with higher concentration of FA and pHBA. However, iWUE increased at all allelochemical concentrations. At the whole plant level, both PSM showed pronounced growth-inhibitory effects on PBM and C and N concentration, root fresh/dry weight, leaf fresh/dry weight, and root, shoot length of C3 broad leaf weed R. acetosa. Carbon isotope discrimination (Δ) was correlated with the dry matter to transpiration ratio (transpiration efficiency) in this C3 species, but its heritability and relationship to R. acetosa growth are less clear. Our FA and pHBA compounds are the potent and selective carbon isotope composition (δ13C) inhibitors known to date. These results confirm the phytotoxicity of FA and pHBA on R. acetosa seedlings, the reduction of relative water content and the induction of carbon isotope discrimination (Δ) with lower plant biomass. Full article
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20 pages, 1081 KiB  
Review
Essential Oils as Feed Additives—Future Perspectives
by Zora Dajić Stevanović, Jasna Bošnjak-Neumüller, Ivana Pajić-Lijaković, Jog Raj and Marko Vasiljević
Molecules 2018, 23(7), 1717; https://doi.org/10.3390/molecules23071717 - 14 Jul 2018
Cited by 114 | Viewed by 10858
Abstract
The inconsistency of phytogenic feed additives’ (PFA) effects on the livestock industry poses a risk for their use as a replacement for antibiotic growth promoters. The livestock market is being encouraged to use natural growth promotors, but information is limited about the PFA [...] Read more.
The inconsistency of phytogenic feed additives’ (PFA) effects on the livestock industry poses a risk for their use as a replacement for antibiotic growth promoters. The livestock market is being encouraged to use natural growth promotors, but information is limited about the PFA mode of action. The aim of this paper is to present the complexity of compounds present in essential oils (EOs) and factors that influence biological effects of PFA. In this paper, we highlight various controls and optimization parameters that influence the processes for the standardization of these products. The chemical composition of EOs depends on plant genetics, growth conditions, development stage at harvest, and processes of extracting active compounds. Their biological effects are further influenced by the interaction of phytochemicals and their bioavailability in the gastrointestinal tract of animals. PFA effects on animal health and production are also complex due to various EO antibiotic, antioxidant, anti-quorum sensing, anti-inflammatory, and digestive fluids stimulating activities. Research must focus on reliable methods to identify and control the quality and effects of EOs. In this study, we focused on available microencapsulation techniques of EOs to increase the bioavailability of active compounds, as well as their application in the animal feed additive industry. Full article
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15 pages, 1076 KiB  
Article
Metabolites and Biological Activities of Thymus zygis, Thymus pulegioides, and Thymus fragrantissimus Grown under Organic Cultivation
by Andrea F. Afonso, Olívia R. Pereira, Mónica Válega, Artur M. S. Silva and Susana M. Cardoso
Molecules 2018, 23(7), 1514; https://doi.org/10.3390/molecules23071514 - 22 Jun 2018
Cited by 36 | Viewed by 5276
Abstract
Thymus plants are marketed for diverse usages because of their pleasant odor, as well as high nutritional value and wealth of health-promoting phytochemicals. In this study, Thymuszygis, Thymuspulegioides, and Thymusfragrantissimus grown under organic cultivation regime were characterized regarding [...] Read more.
Thymus plants are marketed for diverse usages because of their pleasant odor, as well as high nutritional value and wealth of health-promoting phytochemicals. In this study, Thymuszygis, Thymuspulegioides, and Thymusfragrantissimus grown under organic cultivation regime were characterized regarding nutrients and phenolic compounds. In addition, the antioxidant and antibacterial properties of these species were screened. The plants were particularly notable for their high K/Na ratio, polyunsaturated fatty acids content and low omega-6/omega-3 fatty acids ratios, which are valuable features of a healthy diet. Caffeic acid and/or its derivatives, mainly rosmarinic acid and caffeoyl rosmarinic acid, represented the majority of the phenolic constituents of these plants, although they were less representative in T. pulegioides, which in turn was the richest in flavones. The latter species also exhibited the highest antioxidant capacity (DPPH EC50 of 9.50 ± 1.98 μg/mL and reducing power EC50 of 30.73 ± 1.48 μg/mL), while T. zygis was the most active towards Gram-positive and Gram-negative bacteria. Overall, the results suggest that the three thyme plants grown in organic farming are endowed with valuable metabolites that give them high commercial value for applications in different industries. Full article
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10 pages, 2332 KiB  
Article
Correlation of FT-IR Fingerprint and α-Glucosidase Inhibitory Activity of Salak (Salacca zalacca) Fruit Extracts Utilizing Orthogonal Partial Least Square
by Mohammed S. M. Saleh, Mohammad Jamshed Siddiqui, Siti Zaiton Mat So’ad, Fatimah Opeyemi Roheem, Salima Saidi-Besbes and Alfi Khatib
Molecules 2018, 23(6), 1434; https://doi.org/10.3390/molecules23061434 - 13 Jun 2018
Cited by 17 | Viewed by 5442
Abstract
Salak fruit (Salacca zalacca), commonly known as snake fruit, is used indigenously as food and for medicinal applications in Southeast Asia. This study was conducted to evaluate the α-glucosidase inhibitory activity of salak fruit extracts in correlation to its Fourier transform [...] Read more.
Salak fruit (Salacca zalacca), commonly known as snake fruit, is used indigenously as food and for medicinal applications in Southeast Asia. This study was conducted to evaluate the α-glucosidase inhibitory activity of salak fruit extracts in correlation to its Fourier transform infrared spectroscopy (FT-IR) fingerprint, utilizing orthogonal partial least square. This calibration model was applied to develop a rapid analytical method tool for quality control of this fruit. A total of 36 extracts prepared with different solvent ratios of ethanol–water (100, 80, 60, 40.20, 0% v/v) and their α-glucosidase inhibitory activities determined. The FT-IR spectra of ethanol–water extracts measured in the region of 400 and 4000 cm−1 at a resolution of 4 cm−1. Multivariate analysis with a combination of orthogonal partial least-squares (OPLS) algorithm was used to correlate the bioactivity of the samples with the FT-IR spectral data. The OPLS biplot model identified several functional groups (C–H, C=O, C–N, N–H, C–O, and C=C) which actively induced α-glucosidase inhibitory activity. Full article
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32 pages, 5558 KiB  
Review
An Overview of Biotransformation and Toxicity of Diterpenes
by Ingrid P. De Sousa, Maria V. Sousa Teixeira and Niege A. Jacometti Cardoso Furtado
Molecules 2018, 23(6), 1387; https://doi.org/10.3390/molecules23061387 - 08 Jun 2018
Cited by 44 | Viewed by 6946
Abstract
Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture. There is great interest [...] Read more.
Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture. There is great interest in developing methods to obtain derivatives of these compounds, and biotransformation processes are interesting tools for the structural modification of natural products with complex chemical structures. Biotransformation processes also have a crucial role in drug development and/or optimization. The understanding of the metabolic pathways for both phase I and II biotransformation of new drug candidates is mandatory for toxicity and efficacy evaluation and part of preclinical studies. This review presents an overview of biotransformation processes of diterpenes carried out by microorganisms, plant cell cultures, animal and human liver microsomes, and rats, chickens, and swine in vivo and highlights the main enzymatic reactions involved in these processes and the role of diterpenes that may be effectively exploited by other fields. Full article
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12 pages, 3988 KiB  
Article
Novel Neuroprotective Lead Compound Ligustrazine Derivative Mass Spectrometry Fragmentation Rule and Metabolites in Rats by LC/LTQ-Orbitrap MS
by Xinyu Zhang, Rui Zhao, Meng Chen, Tao Ma, Gaorong Wu, Nannan Xue, Guoliang Li, Hui Wang, Kang Fang, Wenxi Zhang, Penglong Wang and Haimin Lei
Molecules 2018, 23(5), 1154; https://doi.org/10.3390/molecules23051154 - 11 May 2018
Cited by 3 | Viewed by 3693
Abstract
The neuroprotective evaluation of ligustrazine derivatives has become a research focus all over the world. A novel ligustrazine derivative, (3,5,6-Trimethylpyrazin-2-yl)methyl(E)-3-(4-((3,5,6-trimethylpyrazin-2-l)methoxy)phenyl)acrylate (T-CA), has shown protective effects against CoCl2-induced neurotoxicity in a differentiated PC12 cell model and middle cerebral artery occlusion (MCAO) model [...] Read more.
The neuroprotective evaluation of ligustrazine derivatives has become a research focus all over the world. A novel ligustrazine derivative, (3,5,6-Trimethylpyrazin-2-yl)methyl(E)-3-(4-((3,5,6-trimethylpyrazin-2-l)methoxy)phenyl)acrylate (T-CA), has shown protective effects against CoCl2-induced neurotoxicity in a differentiated PC12 cell model and middle cerebral artery occlusion (MCAO) model in our previous studies. However, nearly none of the parent drugs existed after rapid metabolism due to uncertain reasons. Thus, the fragmentation regularities of mass spectra, and metabolites, of T-CA in rats were examined using liquid chromatography-electrospray ionizationion trap mass spectrometry (LC/LTQ-Orbitrap MS) in this research. The main fragment ion, mass spectrum characteristics, and the structural information were elucidated. When compared with a blank sample, we identified five kinds of T-CA metabolites, including three phase I metabolites and two phase II metabolites. The results showed that the metabolic pathways of T-CA in rats via oral administration were hydrolysis (ether bond rupture, ester bond rupture), oxidation, reduction, glucose aldehyde acidification, etc. In addition, three main metabolites were synthesized and their structures were identified by superconducting high-resolution NMR and high-resolution mass spectroscopy (HR-MS). The neuroprotective activity of these metabolites was validated in a PC12 cell model. One of the metabolites (M2) showed significant activity (EC50 = 9.67 μM), which was comparable to the prototype drug T-CA (EC50 = 7.97 μM). The current study provides important information for ligustrazine derivatives, pertaining to the biological conversion process in vivo. Full article
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8 pages, 444 KiB  
Article
Bioactivity-Guided Isolation of Antimicrobial and Antioxidant Metabolites from the Mushroom Tapinella atrotomentosa
by Zoltán Béni, Miklós Dékány, Bernadett Kovács, Boglárka Csupor-Löffler, Zoltán Péter Zomborszki, Erika Kerekes, András Szekeres, Edit Urbán, Judit Hohmann and Attila Ványolós
Molecules 2018, 23(5), 1082; https://doi.org/10.3390/molecules23051082 - 04 May 2018
Cited by 25 | Viewed by 5660
Abstract
Bioassay-guided fractionation of the chloroform extract of Tapinella atrotomentosa led to the isolation of four secondary metabolites 14. Two of the compounds are lactones—osmundalactone (1) and 5-hydroxy-hex-2-en-4-olide (2)—while 3 and 4 were identified as terphenyl quinones, [...] Read more.
Bioassay-guided fractionation of the chloroform extract of Tapinella atrotomentosa led to the isolation of four secondary metabolites 14. Two of the compounds are lactones—osmundalactone (1) and 5-hydroxy-hex-2-en-4-olide (2)—while 3 and 4 were identified as terphenyl quinones, spiromentins C and B, respectively. The structures of the compounds were established on the basis of NMR and MS spectroscopic analysis. The isolated fungal metabolites were evaluated for their antibacterial activities against several Gram-positive and negative bacteria. In addition, their synergistic effect with cefuroxime against methicillin-resistant Staphylococcus aureus (MRSA) was also evaluated. Compounds 13 proved to possess significant antibacterial activity against multiresistant Acinetobacter baumannii and extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. The investigation of the antioxidant effect of the isolated compounds in DPPH and ORAC assays revealed that spiromentins C (3) and B (4) have remarkable antioxidant activity. Full article
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11 pages, 490 KiB  
Article
The Chemical Composition and Metabolic Effects of Attalea phalerata Nut Oil in Hyperlipidemic Rats Induced by a High-Fructose Diet
by Débora Da Silva Baldivia, Eliana Janet Sanjinez-Argandonã, Kátia Ávila Antunes, Izabel Cristina Freitas Moraes, Edson Lucas Dos Santos and Kely De Picoli Souza
Molecules 2018, 23(4), 960; https://doi.org/10.3390/molecules23040960 - 20 Apr 2018
Cited by 5 | Viewed by 3956
Abstract
The fatty acids found in nuts are important regulators of the metabolism. These acids are frequently associated with a reduction of serum cholesterol and body fat and a lower risk of developing cardiovascular disease. In this context, the aim of this study was [...] Read more.
The fatty acids found in nuts are important regulators of the metabolism. These acids are frequently associated with a reduction of serum cholesterol and body fat and a lower risk of developing cardiovascular disease. In this context, the aim of this study was to identify and quantify the nut oil fatty acids from Attalea phalerata and investigate their metabolic effects in rats with hyperlipidemia induced by a diet rich in fructose. Oleic and lauric acids were the major compounds found in the A. phalerata nut oil (APNO). Hyperlipidemic rats treated with APNO showed a reduction in the total serum cholesterol similar to those treated with simvastatin, an increased body temperature by 1 °C, and a reduction in the body weight gain and mesenteric depot of white adipose tissue compared to the hyperlipidemic controls rats. There was an increase in the relative liver weight of rats treated with APNO, without, however, any change in the serum markers of hepatic toxicity. In addition, there was an increase in the moisture and lipid content of the feces of the rats treated with APNO compared to the controls. Together, these results suggest that APNO has potential use in health foods and nutritional supplements to control hypercholesterolemia and obesity. Full article
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25 pages, 924 KiB  
Review
Stryphnodendron Species Known as “Barbatimão”: A Comprehensive Report
by Tatiana M. Souza-Moreira, Geisiany M. Queiroz-Fernandes and Rosemeire C. L. R. Pietro
Molecules 2018, 23(4), 910; https://doi.org/10.3390/molecules23040910 - 15 Apr 2018
Cited by 30 | Viewed by 6190
Abstract
Stryphnodendron spp., popularly known as “barbatimão”, is the native Brazilian tree most often employed to treat wounds and infections. The aim of the present study was to highlight the importance of S. adstringens, as well as other Stryphnodendron species recognized as “barbatimão”, to [...] Read more.
Stryphnodendron spp., popularly known as “barbatimão”, is the native Brazilian tree most often employed to treat wounds and infections. The aim of the present study was to highlight the importance of S. adstringens, as well as other Stryphnodendron species recognized as “barbatimão”, to human health, depicting the relevance of ethnopharmacological knowledge to scientific evidence for uses, related chemical compounds, development of pharmaceutical formulations, and the establishment of toxicity parameters. For this purpose, the literature databases PubMed, Scielo, Lilacs, CAPES Thesis and Google Scholar were searched until 2017. It was observed that stem bark was the primary part of the plant used, mainly as a decoction, for wound healing and treatment of infectious and inflammatory disorders. Confirmed biological activities, including wound healing, anti-inflammatory, antioxidant, and antimicrobial activities, were related to the presence of compounds from tannin class, mostly proanthocyanidins. Toxicity parameters for stem bark were inconclusive, but toxicity was observed to a significant extent when seeds were ingested by cattle or other animals. Due to these important and confirmed biological activities, government policy encourages the phytotherapic use of S. adstringens, and some formulations with stem bark extracts were developed and patented. Furthermore, antiprotozoal, hypoglycemic and antiviral activities were identified as promising. Full article
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15 pages, 1808 KiB  
Article
UFLC-Q-TOF-MS/MS-Based Screening and Identification of Flavonoids and Derived Metabolites in Human Urine after Oral Administration of Exocarpium Citri Grandis Extract
by Xuan Zeng, Weiwei Su, Yuying Zheng, Hong Liu, Panlin Li, Weijian Zhang, Yuting Liang, Yang Bai, Wei Peng and Hongliang Yao
Molecules 2018, 23(4), 895; https://doi.org/10.3390/molecules23040895 - 12 Apr 2018
Cited by 68 | Viewed by 6523
Abstract
Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM) for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in [...] Read more.
Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM) for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in human have not been well investigated. ECG was extracted using boiling water and then provided to volunteers for oral administration. Following the ingestion, urine samples were collected from volunteers over 48 h. The extract and urine samples were analyzed using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS) system to screen and identify flavonoids and derived in vivo metabolites. A total of 18 flavonoids were identified in the ECG extract, and 20 metabolites, mainly glucuronide and sulfate conjugates, were screened in urine samples collected post consumption. The overall excretion of naringenin metabolites corresponded to 5.45% of intake and occurred mainly within 4–12 h after the ingestion. Meanwhile, another 29 phenolic catabolites were detected in urine. Obtained data revealed that flavonoids were abundant in the ECG extract, and these components underwent extensive phase II metabolism in humans. These results provided valuable information for further study of the pharmacology and mechanism of action of ECG. Full article
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12 pages, 9466 KiB  
Article
Extracellular Phytase Production by the Wine Yeast S. cerevisiae (Finarome Strain) during Submerged Fermentation
by Grzegorz Kłosowski, Dawid Mikulski and Oliwia Jankowiak
Molecules 2018, 23(4), 848; https://doi.org/10.3390/molecules23040848 - 08 Apr 2018
Cited by 14 | Viewed by 5109
Abstract
One of the key steps in the production of phytases of microbial origin is selection of culture parameters, followed by isolation of the enzyme and evaluation of its catalytic activity. It was found that conditions for S. cerevisiae yeast culture, strain Finarome, giving [...] Read more.
One of the key steps in the production of phytases of microbial origin is selection of culture parameters, followed by isolation of the enzyme and evaluation of its catalytic activity. It was found that conditions for S. cerevisiae yeast culture, strain Finarome, giving the reduction in phytic acid concentration of more than 98% within 24 h of incubation were as follows: pH 5.5, 32 °C, continuous stirring at 80 rpm, the use of mannose as a carbon source and aspartic acid as a source of nitrogen. The highest catalytic activity of the isolated phytase was observed at 37 °C, pH 4.0 and using phytate as substrate at concentration of 5.0 mM. The presence of ethanol in the medium at a concentration of 12% v/v reduces the catalytic activity to above 60%. Properties of phytase derived from S. cerevisiae yeast culture, strain Finarome, indicate the possibility of its application in the form of a cell’s free crude protein isolate for the hydrolysis of phytic acid to improve the efficiency of alcoholic fermentation processes. Our results also suggest a possibility to use the strain under study to obtain a fusant derived with specialized distillery strains, capable of carrying out a highly efficient fermentation process combined with the utilization of phytates. Full article
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15 pages, 1548 KiB  
Article
Variable Levels of Tolerance to Water Stress (Drought) and Associated Biochemical Markers in Tunisian Barley Landraces
by Sameh Dbira, Mohamad Al Hassan, Pietro Gramazio, Ali Ferchichi, Oscar Vicente, Jaime Prohens and Monica Boscaiu
Molecules 2018, 23(3), 613; https://doi.org/10.3390/molecules23030613 - 08 Mar 2018
Cited by 26 | Viewed by 4272
Abstract
Due to its high tolerance to abiotic stress, barley (Hordeum vulgare) is cultivated in many arid areas of the world. In the present study, we evaluate the tolerance to water stress (drought) in nine accessions of “Ardhaoui” barley landraces from different [...] Read more.
Due to its high tolerance to abiotic stress, barley (Hordeum vulgare) is cultivated in many arid areas of the world. In the present study, we evaluate the tolerance to water stress (drought) in nine accessions of “Ardhaoui” barley landraces from different regions of Tunisia. The genetic diversity of the accessions is evaluated with six SSR markers. Seedlings from the nine accessions are subjected to water stress by completely stopping irrigation for three weeks. A high genetic diversity is detected among the nine accessions, with no relationships between genetic distance and geographical or ecogeographical zone. The analysis of growth parameters and biochemical markers in the water stress-treated plants in comparison to their respective controls indicated great variability among the studied accessions. Accession 2, from El May Island, displayed high tolerance to drought. Increased amounts of proline in water-stressed plants could not be correlated with a better response to drought, as the most tolerant accessions contained lower levels of this osmolyte. A good correlation was established between the reduction of growth and degradation of chlorophylls and increased levels of malondialdehyde and total phenolics. These biochemical markers may be useful for identifying drought tolerant materials in barley. Full article
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10 pages, 2325 KiB  
Article
Quantitative 1H-NMR Spectroscopy for Profiling Primary Metabolites in Mulberry Leaves
by Qianqian Liang, Qiuying Wang, Yuan Wang, Ya-nan Wang, Jia Hao and Miaomiao Jiang
Molecules 2018, 23(3), 554; https://doi.org/10.3390/molecules23030554 - 02 Mar 2018
Cited by 11 | Viewed by 10141
Abstract
The primary metabolites in aqueous extract of mulberry (Morus alba L.) leaves were characterized by using proton nuclear magnetic resonance (1H-NMR) spectroscopy. With the convenience of resonance assignment, GABA together with the other 10 primary metabolites was simultaneously identified and [...] Read more.
The primary metabolites in aqueous extract of mulberry (Morus alba L.) leaves were characterized by using proton nuclear magnetic resonance (1H-NMR) spectroscopy. With the convenience of resonance assignment, GABA together with the other 10 primary metabolites was simultaneously identified and quantified in one 1H-NMR spectrum. In this study, external calibration curves for metabolites were employed to calculate the concentrations of interests. The proposed quantitative approach was demonstrated with good linearity (r2 ranged in the interval of 0.9965–0.9999), precision, repeatability, stability (RSD values in the ranges of 0.35–4.89%, 0.77–7.13% and 0.28–2.33%, respectively) and accuracy (recovery rates from 89.2% to 118.5%). The established 1H-NMR method was then successfully applied to quantify 11 primary metabolites in mulberry leaves from different geographical regions within a rapid analysis time and a simple sample preparation procedure. Full article
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13 pages, 1455 KiB  
Article
Bivariate Correlation Analysis of the Chemometric Profiles of Chinese Wild Salvia miltiorrhiza Based on UPLC-Qqq-MS and Antioxidant Activities
by Xiaodan Zhang, Yange Yu, Yesheng Cen, Dongfeng Yang, Zhechen Qi, Zhuoni Hou, Shuanglai Han, Zengxuan Cai and Kuancheng Liu
Molecules 2018, 23(3), 538; https://doi.org/10.3390/molecules23030538 - 28 Feb 2018
Cited by 25 | Viewed by 4576
Abstract
To better understand the mechanisms underlying the pharmacological actions of Salvia miltiorrhiza, correlation between the chemical profiles and in vitro antioxidant activities in 50 batches of wild S. miltiorrhiza samples was analyzed. Our ultra-performance liquid chromatography–tandem mass spectrometry analysis detected twelve phenolic [...] Read more.
To better understand the mechanisms underlying the pharmacological actions of Salvia miltiorrhiza, correlation between the chemical profiles and in vitro antioxidant activities in 50 batches of wild S. miltiorrhiza samples was analyzed. Our ultra-performance liquid chromatography–tandem mass spectrometry analysis detected twelve phenolic acids and five tanshinones and obtained various chemical profiles from different origins. In a principal component analysis (PCA) and cluster analysis, the tanshinones cryptotanshinone, tanshinone IIA and dihydrotanshinone I exhibited higher weights in PC1, whereas the phenolic acids danshensu, salvianolic acids A and B and lithospermic acid were highly loaded in PC2. All components could be optimized as markers of different locations and might be suitable for S. miltiorrhiza quality analyses. Additionally, the DPPH and ABTS assays used to comprehensively evaluate antioxidant activities indicated large variations, with mean DPPH and ABTS scavenging potencies of 32.24 and 23.39 μg/mL, respectively, among S. miltiorrhiza extract solutions. Notably, samples that exceeded the mean IC50 values had higher phenolic acid contents. A correlation analysis indicated a strong correlation between the antioxidant activities and phenolic acid contents. Caffeic acid, danshensu, rosmarinic acid, lithospermic acid and salvianolic acid B were major contributors to antioxidant activity. In conclusion, phenolic compounds were the predominant antioxidant components in the investigated plant species. These plants may be sources of potent natural antioxidants and beneficial chemopreventive agents. Full article
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11 pages, 760 KiB  
Review
Sulphated Flavonoids: Biosynthesis, Structures, and Biological Activities
by Yanna C. F. Teles, Maria Sallett R. Souza and Maria De Fátima Vanderlei de Souza
Molecules 2018, 23(2), 480; https://doi.org/10.3390/molecules23020480 - 23 Feb 2018
Cited by 98 | Viewed by 7886
Abstract
The great diversity of enzymatic reactions in plant secondary metabolism allows the continuous discovery of new natural compounds and derivatives. Flavonoids, for example, can be found as aglycone or as several sorts of glycosylated, acetylated, methylated, and sulphated derivatives. This review focuses on [...] Read more.
The great diversity of enzymatic reactions in plant secondary metabolism allows the continuous discovery of new natural compounds and derivatives. Flavonoids, for example, can be found as aglycone or as several sorts of glycosylated, acetylated, methylated, and sulphated derivatives. This review focuses on sulphated flavonoids, an uncommon group of flavonoid derivatives found in some plant families. This work presents a compilation of sulphated flavonoids and their natural sources reported in the literature. Biosynthetic aspects and biological activities have also been reviewed, showing that these particular kinds of natural compounds play an interesting role in plant metabolism, as well as being potential candidates for the development of new drugs. Full article
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17 pages, 1779 KiB  
Article
Dynamic Changes in Phenolics and Antioxidant Capacity during Pecan (Carya illinoinensis) Kernel Ripening and Its Phenolics Profiles
by Xiaodong Jia, Huiting Luo, Mengyang Xu, Min Zhai, Zhongren Guo, Yushan Qiao and Liangju Wang
Molecules 2018, 23(2), 435; https://doi.org/10.3390/molecules23020435 - 16 Feb 2018
Cited by 46 | Viewed by 4643
Abstract
Pecan (Carya illinoinensis) kernels have a high phenolics content and a high antioxidant capacity compared to other nuts—traits that have attracted great interest of late. Changes in the total phenolic content (TPC), condensed tannins (CT), total flavonoid content (TFC), five individual [...] Read more.
Pecan (Carya illinoinensis) kernels have a high phenolics content and a high antioxidant capacity compared to other nuts—traits that have attracted great interest of late. Changes in the total phenolic content (TPC), condensed tannins (CT), total flavonoid content (TFC), five individual phenolics, and antioxidant capacity of five pecan cultivars were investigated during the process of kernel ripening. Ultra-performance liquid chromatography coupled with quadruple time-of-flight mass (UPLC-Q/TOF-MS) was also used to analyze the phenolics profiles in mixed pecan kernels. TPC, CT, TFC, individual phenolics, and antioxidant capacity were changed in similar patterns, with values highest at the water or milk stages, lowest at milk or dough stages, and slightly varied at kernel stages. Forty phenolics were tentatively identified in pecan kernels, of which two were first reported in the genus Carya, six were first reported in Carya illinoinensis, and one was first reported in its kernel. The findings on these new phenolic compounds provide proof of the high antioxidant capacity of pecan kernels. Full article
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10 pages, 1361 KiB  
Article
Xylosylated Detoxification of the Rice Flavonoid Phytoalexin Sakuranetin by the Rice Sheath Blight Fungus Rhizoctonia solani
by Shun Katsumata, Hiroaki Toshima and Morifumi Hasegawa
Molecules 2018, 23(2), 276; https://doi.org/10.3390/molecules23020276 - 29 Jan 2018
Cited by 18 | Viewed by 5651
Abstract
Sakuranetin (1) is a rice flavanone-type phytoalexin. We have already reported that the metabolites from the detoxification of 1 by Pyricularia oryzae are naringenin (2) and sternbin. In this study, we investigated whether the rice sheath blight fungus Rhizoctonia [...] Read more.
Sakuranetin (1) is a rice flavanone-type phytoalexin. We have already reported that the metabolites from the detoxification of 1 by Pyricularia oryzae are naringenin (2) and sternbin. In this study, we investigated whether the rice sheath blight fungus Rhizoctonia solani, another major rice pathogen, can detoxify 1. The extract of R. solani suspension culture containing 1 was analyzed by LC-MS to identify the metabolites of 1. Three putative metabolites of 1 were detected in the extract from the R. solani suspension culture 12 h after the addition of 1, and they were identified as 2, sakuranetin-4′-O-β-d-xylopyranoside (3), and naringenin-7-O-β-d-xylopyranoside (4) by NMR, LC-MS/MS, and GC-MS analyses. The accumulation of 2, 3, and 4 reached their maximum levels 9–12 h after the addition of 1, whereas the content of 1 decreased to almost zero within 9 h. The antifungal activities of 3 and 4 against R. solani were negligible, and 2 showed weaker antifungal activity than 1. We concluded that 2, 3, and 4 are metabolites from the detoxification of 1 by R. solani. Xylosylation is a rare and efficient detoxification method for phytoalexins. Full article
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20 pages, 1916 KiB  
Article
High-Resolution Lipidomics of the Early Life Stages of the Red Seaweed Porphyra dioica
by Elisabete Da Costa, Vitor Azevedo, Tânia Melo, Andreia M. Rego, Dmitry V. Evtuguin, Pedro Domingues, Ricardo Calado, Rui Pereira, Maria H. Abreu and Maria R. Domingues
Molecules 2018, 23(1), 187; https://doi.org/10.3390/molecules23010187 - 17 Jan 2018
Cited by 33 | Viewed by 5963
Abstract
Porphyra dioica is a commercial seaweed consumed all over the world, mostly in the shape of nori sheets used for “sushi” preparation. It is a well-known part of the Asian diet with health benefits, which have been associated, among others, to the high [...] Read more.
Porphyra dioica is a commercial seaweed consumed all over the world, mostly in the shape of nori sheets used for “sushi” preparation. It is a well-known part of the Asian diet with health benefits, which have been associated, among others, to the high levels of n-3 and n-6 fatty acids in this red alga. However, other highly valued lipids of Porphyra are polar lipids that remain largely undescribed and can have both nutritional value and bioactivity, thus could contribute to the valorization of this seaweed. In this context, the present work aims to identify the lipidome of two life cycle stages of the Atlantic species Porphyra dioica: the early life stage conchocelis produced in an indoor-nursery, and young blades produced outdoors using an integrated multitrophic aquaculture (IMTA) framework. Both the blades (gametophyte) and conchocelis (sporophyte) are commercialized in the food and cosmetics sectors. Liquid chromatography coupled to Q–Exactive high resolution-mass spectrometry (MS) platform was used to gain insight into the lipidome of these species. Our results allowed the identification of 110 and 100 lipid molecular species in the lipidome of the blade and conchocelis, respectively. These lipid molecular species were distributed as follows (blade/conchocelis): 14/15 glycolipids (GLs), 93/79 phospholipids (PLs), and 3/6 betaine lipids. Both life stages displayed a similar profile of GLs and comprised 20:4(n-6) and 20:5(n-3) fatty acids that contribute to n-3 and n-6 fatty acid pool recorded and rank among the molecular species with higher potential bioactivity. PLs’ profile was different between the two life stages surveyed, mainly due to the number and relative abundance of molecular species. This finding suggests that differences between both life stages were more likely related with shifts in the lipids of extraplastidial membranes rather than in plastidial membranes. PLs contained n-6 and n-3 precursors and in both life stages of Porphyra dioica the n-6/n-3 ratio recorded was less than 2, highlighting the potential benefits of using these life stages in human diet to prevent chronic diseases. Atherogenic and thrombogenic indexes of blades (0.85 and 0.49, respectively) and conchocelis (0.34 and 0.30, respectively) are much lower than those reported for other Rhodophyta, which highlights their potential application as food or as functional ingredients. Overall, MS-based platforms represent a powerful tool to characterize lipid metabolism and target lipids along different life stages of algal species displaying complex life cycles (such as Porphyra dioica), contributing to their biotechnological application. Full article
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24 pages, 10264 KiB  
Article
Rapid Screening and Identification of Daidzein Metabolites in Rats Based on UHPLC-LTQ-Orbitrap Mass Spectrometry Coupled with Data-Mining Technologies
by Wenjing Zhao, Zhanpeng Shang, Qinqing Li, Moran Huang, Wenbin He, Zhibin Wang and Jiayu Zhang
Molecules 2018, 23(1), 151; https://doi.org/10.3390/molecules23010151 - 12 Jan 2018
Cited by 34 | Viewed by 6017
Abstract
Daidzein, the main bioactive soy isoflavone in Nature, has been found to possess many biological functions. It has been investigated in particular as a phytoestrogen owing to the similarity of its structure with that of the human hormone estrogen. Due to the lack [...] Read more.
Daidzein, the main bioactive soy isoflavone in Nature, has been found to possess many biological functions. It has been investigated in particular as a phytoestrogen owing to the similarity of its structure with that of the human hormone estrogen. Due to the lack of comprehensive studies on daidzein metabolism, further research is still required to clarify its in vivo metabolic fate and intermediate processes. In this study, an efficient strategy was established using UHPLC-LTQ-Orbitrap mass spectrometry to profile the metabolism of daidzein in rats. Meanwhile, multiple data-mining methods including high-resolution extracted ion chromatogram (HREIC), multiple mass defect filtering (MMDF), neutral loss fragment (NLF), and diagnostic product ion (DPI) were utilized to investigate daidzein metabolites from the HR-ESI-MS1 to ESI-MSn stage in both positive and negative ion modes. Consequently, 59 metabolites, including prototype compounds, were positively or tentatively elucidated based on reference standards, accurate mass measurements, mass fragmentation behaviors, chromatographic retention times, and corresponding calculated ClogP values. As a result, dehydration, hydrogenation, methylation, dimethylation, glucuronidation, glucosylation, sulfonation, ring-cleavage, and their composite reactions were ascertained to interpret its in vivo biotransformation. Overall, our results not only revealed the potential pharmacodynamics forms of daidzein, but also aid in establishing a practical strategy for rapid screening and identifying metabolites of natural compounds. Full article
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13 pages, 1249 KiB  
Article
Chemical Composition and Evaluation of the Biological Properties of the Essential Oil of the Dietary Phytochemical Lippia citriodora
by Eleni Fitsiou, Gregoria Mitropoulou, Katerina Spyridopoulou, Manolis Vamvakias, Haido Bardouki, Alex Galanis, Katerina Chlichlia, Yiannis Kourkoutas, Mihalis Ι. Panayiotidis and Aglaia Pappa
Molecules 2018, 23(1), 123; https://doi.org/10.3390/molecules23010123 - 12 Jan 2018
Cited by 36 | Viewed by 5901
Abstract
The aim of the study was to characterize the chemical composition and biological properties of the essential oil from the plant Lippia citriodora grown in Greece. The essential oil volatiles were analyzed by gas chromatography–mass spectrometry GC-MS indicating citral as the major component. [...] Read more.
The aim of the study was to characterize the chemical composition and biological properties of the essential oil from the plant Lippia citriodora grown in Greece. The essential oil volatiles were analyzed by gas chromatography–mass spectrometry GC-MS indicating citral as the major component. Τhe antimicrobial properties were assayed using the disk diffusion method and the minimum inhibitory and non-inhibitory concentration values were determined. Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus, Saccharomyces cerevisiae, and Aspergillus niger were sensitive to Lippia citriodora oil, but not Escherichia coli, Salmonella Enteritidis, Salmonella typhimurium, and Pseudomonas fragi. Adversely, all microbes tested were sensitive to citral. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays were used to assess direct antioxidant activity, which proved to be weak for both agents, while comet assay was utilized to study the cytoprotective effects against H2O2-induced oxidative damage in Jurkat cells. Interestingly, the oil showed a more profound cytoprotective effect compared to citral. The antiproliferative activity was evaluated in a panel of cancer cell lines using the sulforhodamine B (SRB) and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-S-(phenylamino) carbonyl-2-tetrazolium hydroxide (XTT) assays and both agents demonstrated potent antiproliferative activity with citral being more cytotoxic than the oil. Taken together, the essential oil of Lippia citriodora and its major component, citral, exert diverse biological properties worthy of further investigation. Full article
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14 pages, 1365 KiB  
Article
Effects of Agitation, Aeration and Temperature on Production of a Novel Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on Volumetric Oxygen Transfer Coefficient
by Yong Zhou, Li-Rong Han, Hong-Wei He, Bu Sang, Dai-Lin Yu, Jun-Tao Feng and Xing Zhang
Molecules 2018, 23(1), 125; https://doi.org/10.3390/molecules23010125 - 11 Jan 2018
Cited by 80 | Viewed by 7144
Abstract
The effects of temperature, agitation and aeration on glycoprotein GP-1 production by Streptomyces kanasenisi ZX01 in bench-scale fermentors were systematically investigated. The maximum final GP-1 production was achieved at an agitation speed of 200 rpm, aeration rate of 2.0 vvm and temperature of [...] Read more.
The effects of temperature, agitation and aeration on glycoprotein GP-1 production by Streptomyces kanasenisi ZX01 in bench-scale fermentors were systematically investigated. The maximum final GP-1 production was achieved at an agitation speed of 200 rpm, aeration rate of 2.0 vvm and temperature of 30 °C. By using a dynamic gassing out method, the effects of agitation and aeration on volumetric oxygen transfer coefficient (kLa) were also studied. The values of volumetric oxygen transfer coefficient in the logarithmic phase increased with increase of agitation speed (from 14.53 to 32.82 h−1) and aeration rate (from 13.21 to 22.43 h−1). In addition, a successful scale-up from bench-scale to pilot-scale was performed based on volumetric oxygen transfer coefficient, resulting in final GP-1 production of 3.92, 4.03, 3.82 and 4.20 mg/L in 5 L, 15 L, 70 L and 500 L fermentors, respectively. These results indicated that constant volumetric oxygen transfer coefficient was appropriate for the scale-up of batch fermentation of glycoprotein GP-1 by Streptomyces kanasenisi ZX01, and this scale-up strategy successfully achieved 100-fold scale-up from bench-scale to pilot-scale fermentor. Full article
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18 pages, 3565 KiB  
Article
Contribution of Secondary Metabolites to the Gastroprotective Effect of Aqueous Extract of Ximenia americana L. (Olacaceae) Stem Bark in Rats
by Ticiana Parente Aragão, Lady Dayane Kalline Travassos dos Prazeres, Samara Alves Brito, Pedro José Rolim Neto, Larissa Araújo Rolim, Jackson Roberto Guedes da Silva Almeida, Germana Freire Rocha Caldas and Almir Gonçalves Wanderley
Molecules 2018, 23(1), 112; https://doi.org/10.3390/molecules23010112 - 09 Jan 2018
Cited by 13 | Viewed by 4461
Abstract
Ximenia americana L. (Olacaceae) is used in ethnomedicine as cicatrizant and for the treatment of gastric disorders. This study identified the chemical constituents of the aqueous extract of X. americana (XaAE) and evaluated its antiulcerogenic activity. After lyophilization, XaAE was analyzed by liquid [...] Read more.
Ximenia americana L. (Olacaceae) is used in ethnomedicine as cicatrizant and for the treatment of gastric disorders. This study identified the chemical constituents of the aqueous extract of X. americana (XaAE) and evaluated its antiulcerogenic activity. After lyophilization, XaAE was analyzed by liquid chromatography-mass spectrometry (LC-MS) and its antiulcerogenic effect was evaluated in acute gastric lesions induced by ethanol, acidified ethanol, and indomethacin. Antisecretory action, mucus production and the participation of sulfhydryl groups (–SH) and nitric oxide (NO) were also investigated. The chromatographic analysis identified procyanidins B and C and catechin/epicatechin as major compounds. Oral administration of XaAE (100, 200 and 400 mg/kg) inhibited the gastric lesions induced by ethanol (76.1%, 77.5% and 100%, respectively), acidified ethanol (44.9%, 80.6% and 94.9%, respectively) and indomethacin (56.4%, 52.7% and 64.9%, respectively). XaAE reduced gastric contents and acidity (51.4% and 67.7%, respectively) but did not alter the production of gastric mucus. The reduction of the -SH and NO groups promoted by N-ethylmaleimide (NEM) and Nω-nitro-l-arginine-methyl-ester (L-NAME) respectively, reduced the gastroprotective effect of XaAE. In conclusion, XaAE has gastroprotective activity mediated in part by -SH, NO and antisecretory activity. This antiulcer action was initially correlated to its major constituents, procyanidins B and C and catechin/epicatechin. Full article
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10 pages, 2203 KiB  
Technical Note
SistematX, an Online Web-Based Cheminformatics Tool for Data Management of Secondary Metabolites
by Marcus Tullius Scotti, Chonny Herrera-Acevedo, Tiago Branquinho Oliveira, Renan Paiva Oliveira Costa, Silas Yudi Konno de Oliveira Santos, Ricardo Pereira Rodrigues, Luciana Scotti and Fernando Batista Da-Costa
Molecules 2018, 23(1), 103; https://doi.org/10.3390/molecules23010103 - 03 Jan 2018
Cited by 39 | Viewed by 7944
Abstract
The traditional work of a natural products researcher consists in large part of time-consuming experimental work, collecting biota to prepare and analyze extracts and to identify innovative metabolites. However, along this long scientific path, much information is lost or restricted to a specific [...] Read more.
The traditional work of a natural products researcher consists in large part of time-consuming experimental work, collecting biota to prepare and analyze extracts and to identify innovative metabolites. However, along this long scientific path, much information is lost or restricted to a specific niche. The large amounts of data already produced and the science of metabolomics reveal new questions: Are these compounds known or new? How fast can this information be obtained? To answer these and other relevant questions, an appropriate procedure to correctly store information on the data retrieved from the discovered metabolites is necessary. The SistematX (http://sistematx.ufpb.br) interface is implemented considering the following aspects: (a) the ability to search by structure, SMILES (Simplified Molecular-Input Line-Entry System) code, compound name and species; (b) the ability to save chemical structures found by searching; (c) compound data results include important characteristics for natural products chemistry; and (d) the user can find specific information for taxonomic rank (from family to species) of the plant from which the compound was isolated, the searched-for molecule, and the bibliographic reference and Global Positioning System (GPS) coordinates. The SistematX homepage allows the user to log into the data management area using a login name and password and gain access to administration pages. In this article, we introduced a modern and innovative web interface for the management of a secondary metabolite database. With its multiplatform design, it is able to be properly consulted via the internet and managed from any accredited computer. The interface provided by SistematX contains a wealth of useful information for the scientific community about natural products, highlighting the locations of species from which compounds are isolated. Full article
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2017

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232 KiB  
Review
Biochemical Properties and Neuroprotective Effects of Compounds in Various Species of Berries
by Erin Kelly, Poorva Vyas and John T. Weber
Molecules 2018, 23(1), 26; https://doi.org/10.3390/molecules23010026 - 22 Dec 2017
Cited by 64 | Viewed by 8392
Abstract
Several species of berries, such as blueberries (Vaccinium angustifolium) and lingonberries (Vaccinium vitis-idaea L.), have attracted much scientific attention in recent years, especially due to their reported antioxidant and anti-inflammatory properties. Berries, as with other types of plants, have developed [...] Read more.
Several species of berries, such as blueberries (Vaccinium angustifolium) and lingonberries (Vaccinium vitis-idaea L.), have attracted much scientific attention in recent years, especially due to their reported antioxidant and anti-inflammatory properties. Berries, as with other types of plants, have developed metabolic mechanisms to survive various environmental stresses, some of which involve reactive oxygen species. In addition, the fruits and leaves of berries have high amounts of polyphenols, such as flavonoids, which act as potent antioxidants. These compounds could potentially be beneficial for brain aging and neurodegenerative disorders. There are now several studies documenting the beneficial effects of various berries in cell models of neurotoxicity as well as in vivo models of neurodegenerative disease. In the current review, we discuss the metabolic strategies that plants and animals have developed in order to combat reactive oxygen species. We then discuss issues of bioavailability of various compounds in mammals and provide a synopsis of studies demonstrating the neuroprotective ability of berries and polyphenols. We also summarize findings from our own research group. For example, we have detected various polyphenols in samples of blueberries and lingonberries and have found that the leaves have a much higher antioxidant capacity than the fruits. Extracts from these species have also demonstrated neuroprotective effects in cellular models of toxicity and inflammation, which are being further pursued in animal models. Full article
3882 KiB  
Communication
Antifungal Activity of Ramulus cinnamomi Explored by 1H-NMR Based Metabolomics Approach
by Chunpeng Wan, Pei Li, Chuying Chen, Xuan Peng, Mingxi Li, Ming Chen, Junsong Wang and Jinyin Chen
Molecules 2017, 22(12), 2237; https://doi.org/10.3390/molecules22122237 - 15 Dec 2017
Cited by 26 | Viewed by 5120
Abstract
A 1H nuclear magnetic resonance (NMR)-based approach to metabolomics combined bioassay was used to elucidate the antifungal activity of cinnamaldehyde (the main active compound of Ramulus cinnamomi) isolated from Ramulus cinnamomi (RC). Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of [...] Read more.
A 1H nuclear magnetic resonance (NMR)-based approach to metabolomics combined bioassay was used to elucidate the antifungal activity of cinnamaldehyde (the main active compound of Ramulus cinnamomi) isolated from Ramulus cinnamomi (RC). Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of NMR data was constructed to analyze all the P. italicum data acquired from the control and treatment groups at 4, 8, and 12 h. Metabolic profiles disclosed metabolic changes that were related to the antifungal effects of cinnamaldehyde against P. italicum including oxidative stress, disorder of energy metabolism, amino acids, and nucleic acids metabolism in treatment group. This integrated metabolomics approach provided an effective way to detect the antifungal effects of cinnamaldehyde against P. italicum dynamically. Full article
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8461 KiB  
Review
Bioactive Steroids and Saponins of the Genus Trillium
by Shafiq Ur Rahman, Muhammad Ismail, Muhammad Khurram, Irfan Ullah, Fazle Rabbi and Marcello Iriti
Molecules 2017, 22(12), 2156; https://doi.org/10.3390/molecules22122156 - 05 Dec 2017
Cited by 30 | Viewed by 6202
Abstract
The species of the genus Trillium (Melanthiaceae alt. Trilliaceae) include perennial herbs with characteristic rhizomes mainly distributed in Asia and North America. Steroids and saponins are the main classes of phytochemicals present in these plants. This review summarizes and discusses the current knowledge [...] Read more.
The species of the genus Trillium (Melanthiaceae alt. Trilliaceae) include perennial herbs with characteristic rhizomes mainly distributed in Asia and North America. Steroids and saponins are the main classes of phytochemicals present in these plants. This review summarizes and discusses the current knowledge on their chemistry, as well as the in vitro and in vivo studies carried out on the extracts, fractions and isolated pure compounds from the different species belonging to this genus, focusing on core biological properties, i.e., cytotoxic, antifungal and anti-inflammatory activities. Full article
2780 KiB  
Article
De Novo RNA Sequencing and Expression Analysis of Aconitum carmichaelii to Analyze Key Genes Involved in the Biosynthesis of Diterpene Alkaloids
by Megha Rai, Amit Rai, Noriaki Kawano, Kayo Yoshimatsu, Hiroki Takahashi, Hideyuki Suzuki, Nobuo Kawahara, Kazuki Saito and Mami Yamazaki
Molecules 2017, 22(12), 2155; https://doi.org/10.3390/molecules22122155 - 05 Dec 2017
Cited by 41 | Viewed by 7739
Abstract
Aconitum carmichaelii is an important medicinal herb used widely in China, Japan, India, Korea, and other Asian countries. While extensive research on the characterization of metabolic extracts of A. carmichaelii has shown accumulation of numerous bioactive metabolites including aconitine and aconitine-type diterpene alkaloids, [...] Read more.
Aconitum carmichaelii is an important medicinal herb used widely in China, Japan, India, Korea, and other Asian countries. While extensive research on the characterization of metabolic extracts of A. carmichaelii has shown accumulation of numerous bioactive metabolites including aconitine and aconitine-type diterpene alkaloids, its biosynthetic pathway remains largely unknown. Biosynthesis of these secondary metabolites is tightly controlled and mostly occurs in a tissue-specific manner; therefore, transcriptome analysis across multiple tissues is an attractive method to identify the molecular components involved for further functional characterization. In order to understand the biosynthesis of secondary metabolites, Illumina-based deep transcriptome profiling and analysis was performed for four tissues (flower, bud, leaf, and root) of A. carmichaelii, resulting in 5.5 Gbps clean RNA-seq reads assembled into 128,183 unigenes. Unigenes annotated as possible rate-determining steps of an aconitine-type biosynthetic pathway were highly expressed in the root, in accordance with previous reports describing the root as the accumulation site for these metabolites. We also identified 21 unigenes annotated as cytochrome P450s and highly expressed in roots, which represent candidate unigenes involved in the diversification of secondary metabolites. Comparative transcriptome analysis of A. carmichaelii with A. heterophyllum identified 20,232 orthogroups, representing 30,633 unigenes of A. carmichaelii, gene ontology enrichment analysis of which revealed essential biological process together with a secondary metabolic process to be highly enriched. Unigenes identified in this study are strong candidates for aconitine-type diterpene alkaloid biosynthesis, and will serve as useful resources for further validation studies. Full article
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1474 KiB  
Article
Phenolic Content and Antioxidant Activity in Raw and Denatured Aqueous Extracts from Sprouts and Wheatgrass of Einkorn and Emmer Obtained under Salinity
by Beatrice Falcinelli, Paolo Benincasa, Isabella Calzuola, Lilia Gigliarelli, Stanley Lutts and Valeria Marsili
Molecules 2017, 22(12), 2132; https://doi.org/10.3390/molecules22122132 - 02 Dec 2017
Cited by 20 | Viewed by 4499
Abstract
Total phenolic content (TPC), reducing power (RP), superoxide radical scavenging (RS), and thiobarbituric acid reactive substances (TBARS) production inhibition were measured in raw and denatured aqueous extracts from sprouts and wheatgrass of einkorn and emmer obtained at increasing salinity. Grains were incubated and [...] Read more.
Total phenolic content (TPC), reducing power (RP), superoxide radical scavenging (RS), and thiobarbituric acid reactive substances (TBARS) production inhibition were measured in raw and denatured aqueous extracts from sprouts and wheatgrass of einkorn and emmer obtained at increasing salinity. Grains were incubated and kept at 0, 25, 50, and 100 mM NaCl until either sprout or wheatgrass stage. Additionally, a recovery treatment was included, in which sprouts obtained at 100 mM NaCl were then transferred at 0 mM NaCl until wheatgrass stage. All parameters (TPC, RP, RS, and TBARS production inhibition) increased with sprouting and were highest in wheatgrass. Salinity increased all parameters, but the effect varied with NaCl concentration, genotype, developmental stage, and plant material processing (raw or denatured). Overall, given the delay and limitation of growth at high NaCl concentration, the best compromise appears to be the application of a moderate salinity (25 to 50 mM NaCl). In denatured extracts, TPC, RP, and RS slightly decreased, and TBARS was not affected, which means that antioxidant activity was mainly related to compounds other than enzymes and peptides, and thus it can be assumed to remain after digestion. Thus, supplementing the human diet with einkorn or emmer sprouts and wheatgrass can actually benefit health. Full article
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2684 KiB  
Article
Neuraminidase Inhibitory Activity and Constituent Characterization of Fagopyrum dibotrys
by Xiang Zhang, Yu Cao, Jinhua Li, Ailin Liu, Haibo Liu and Linfang Huang
Molecules 2017, 22(11), 1998; https://doi.org/10.3390/molecules22111998 - 18 Nov 2017
Cited by 8 | Viewed by 4104
Abstract
This study aimed to identify a new biological activity of the widely distributed species Fagopyrum dibotrys. Four F. dibotrys extracts (ethyl acetate (EA), petroleum ether (P), ethanol (E), and water (W)) were explored for their anti-neuraminidase (NA) activity. A total of 32 [...] Read more.
This study aimed to identify a new biological activity of the widely distributed species Fagopyrum dibotrys. Four F. dibotrys extracts (ethyl acetate (EA), petroleum ether (P), ethanol (E), and water (W)) were explored for their anti-neuraminidase (NA) activity. A total of 32 compounds were identified using UHPLC-Q-Exactive Orbitrap HRMS in the EA extract, which had the best NA inhibitory effects. We used the docking data for supporting compounds’ anti-neuraminidase activity. Among them, five compounds including one flavonoid, three organic acids, and one glucoside were discovered for the first time in F. dibotrys. Docking studies and NA activity assay revealed the remarkable NA inhibitory activity of eight components in EA extract, especially rutin, hesperidin, procyanidin B2, and quercitrin. Therefore, F. dibotrys could be used to develop anti-influenza drugs. Full article
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5807 KiB  
Review
Critical Review on the Significance of Olive Phytochemicals in Plant Physiology and Human Health
by Irene Gouvinhas, Nelson Machado, Carla Sobreira, Raúl Domínguez-Perles, Sónia Gomes, Eduardo Rosa and Ana I. R. N. A. Barros
Molecules 2017, 22(11), 1986; https://doi.org/10.3390/molecules22111986 - 16 Nov 2017
Cited by 56 | Viewed by 8578
Abstract
Olive oil displays remarkable organoleptic and nutritional features, which turn it into a foodstuff appreciated by consumers, and a basic component of the Mediterranean diet. Indeed, the noticed benefits of including olive oil in the diet have been assigned to the presence of [...] Read more.
Olive oil displays remarkable organoleptic and nutritional features, which turn it into a foodstuff appreciated by consumers, and a basic component of the Mediterranean diet. Indeed, the noticed benefits of including olive oil in the diet have been assigned to the presence of diverse bioactive compounds with different molecular structures. These compounds confer a wide range of biological properties to this food matrix, including the prevention of distinct human diseases as well as the modulation of their severity. The most relevant bioactive compounds present in olive oil correspond to benzoic and cinnamic acids, phenolic alcohols and secoiridoids, and also flavonoids. Over the last decades, several studies, devoted to gaining a further insight into the relative contribution of the separate groups and individual compounds for their biological activities, have been conducted, providing relevant information on structure–activity relationships. Therefore, this paper critically reviews the health benefits evidenced by distinct phenolic compounds found in olive oils, thus contributing to clarify the relationship between their chemical structures and biological functions, further supporting their interest as essential ingredients of wholesome foods. Full article
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2870 KiB  
Review
The killer of Socrates: Coniine and Related Alkaloids in the Plant Kingdom
by Hannu Hotti and Heiko Rischer
Molecules 2017, 22(11), 1962; https://doi.org/10.3390/molecules22111962 - 14 Nov 2017
Cited by 40 | Viewed by 17362
Abstract
Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine’s most famous victim is Socrates who was sentenced to death [...] Read more.
Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine’s most famous victim is Socrates who was sentenced to death by poison chalice containing poison hemlock in 399 BC. In chemistry, coniine holds two historical records: It is the first alkaloid the chemical structure of which was established (in 1881), and that was chemically synthesized (in 1886). In plants, coniine and twelve closely related alkaloids are known from poison hemlock (Conium maculatum L.), and several Sarracenia and Aloe species. Recent work confirmed its biosynthetic polyketide origin. Biosynthesis commences by carbon backbone formation from butyryl-CoA and two malonyl-CoA building blocks catalyzed by polyketide synthase. A transamination reaction incorporates nitrogen from l-alanine and non-enzymatic cyclization leads to γ-coniceine, the first hemlock alkaloid in the pathway. Ultimately, reduction of γ-coniceine to coniine is facilitated by NADPH-dependent γ-coniceine reductase. Although coniine is notorious for its toxicity, there is no consensus on its ecological roles, especially in the carnivorous pitcher plants where it occurs. Lately there has been renewed interest in coniine’s medical uses particularly for pain relief without an addictive side effect. Full article
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Review
Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases
by Taiwo Betty Ayeleso, Mashudu Given Matumba and Emmanuel Mukwevho
Molecules 2017, 22(11), 1915; https://doi.org/10.3390/molecules22111915 - 13 Nov 2017
Cited by 196 | Viewed by 10989
Abstract
The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA) in the [...] Read more.
The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA) in the prevention and management of chronic diseases. Oleanolic acid is a pentacyclic triterpenoid widely found in plants, including fruits and vegetables with different techniques and chromatography platforms being employed in its extraction and isolation. Several studies have demonstrated the potential therapeutic effects of OA on different diseases and their symptoms. Furthermore, oleanolic acid also serves as a framework for the development of novel semi-synthetic triterpenoids that could prove vital in finding therapeutic modalities for various ailments. There are recent advances in the design and synthesis of chemical derivatives of OA to enhance its solubility, bioavailability and potency. Some of these derivatives have also been therapeutic candidates in a number of clinical trials. This review consolidates and expands on recent reports on the biological effects of oleanolic acid from different plant sources and its synthetic derivatives as well as their mechanisms of action in in vitro and in vivo study models. This review suggests that oleanolic acid and its derivatives are important candidates in the search for alternative therapy in the treatment and management of chronic diseases. Full article
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Article
1H-NMR-Based Metabonomics of the Protective Effect of Coptis chinensis and Berberine on Cinnabar-Induced Hepatotoxicity and Nephrotoxicity in Rats
by Guangyue Su, Haifeng Wang, Yuxian Gao, Gang Chen, Yuehu Pei and Jiao Bai
Molecules 2017, 22(11), 1855; https://doi.org/10.3390/molecules22111855 - 02 Nov 2017
Cited by 19 | Viewed by 5597
Abstract
Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which [...] Read more.
Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which include hepatoprotective effects on liver injuries, has been studied intensively, yet the therapy of liver injuries and underlying mechanism remain unclear. We investigated the detoxification mechanism of Coptis chinensis and berberine using metabolomics of urine and serum in the present study. After the treatment with Coptis chinensis and berberine, compared with the cinnabar group, Coptis chinensis and berberine can regulate the concentration of the endogenous metabolites. PLS-DA score plots demonstrated that the urine and serum metabolic profiles in rats of the Coptis chinensis and berberine groups were similar those of the control group, yet remarkably apart from the cinnabar group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism and metabolism of intestinal flora in rats. Meanwhile, liver and kidney histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabonomics. Full article
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Review
Cyclodipeptides: An Overview of Their Biosynthesis and Biological Activity
by Awdhesh Kumar Mishra, Jaehyuk Choi, Seong-Jin Choi and Kwang-Hyun Baek
Molecules 2017, 22(10), 1796; https://doi.org/10.3390/molecules22101796 - 23 Oct 2017
Cited by 86 | Viewed by 9276
Abstract
Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and [...] Read more.
Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters. In this review, we provide a comprehensive summary of CDP biosynthetic pathways and modifying enzymes. We also discuss the biological properties of some known CDPs and their possible applications in metabolic engineering. Full article
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Article
Identification of Metabolites of the Cardioprotective Alkaloid Dehydrocorydaline in Rat Plasma and Bile by Liquid Chromatography Coupled with Triple Quadrupole Linear Ion Trap Mass Spectrometry
by Huanyu Guan, Kaitong Li, Xiaoming Wang, Xiaomei Luo, Meifeng Su, Wenting Tan, Xiaoyan Chang and Yue Shi
Molecules 2017, 22(10), 1686; https://doi.org/10.3390/molecules22101686 - 10 Oct 2017
Cited by 11 | Viewed by 4764
Abstract
Dehydrocorydaline (DHC), a quaternary alkaloid from Corydalis yanhusuo, has been demonstrated to be the active constituent in the treatment of coronary heart disease. In this study, a high-performance liquid chromatography–electrospray ionization–triple quadrupole linear ion trap mass spectrometry (HPLC–ESI–QTRAP MS) technique was used [...] Read more.
Dehydrocorydaline (DHC), a quaternary alkaloid from Corydalis yanhusuo, has been demonstrated to be the active constituent in the treatment of coronary heart disease. In this study, a high-performance liquid chromatography–electrospray ionization–triple quadrupole linear ion trap mass spectrometry (HPLC–ESI–QTRAP MS) technique was used to identify DHC metabolites in plasma and bile after oral administration of DHC to rats. A total of 18 metabolites (M1 to M18) were identified and characterized by LC–MS/MS in the positive ion mode. These 18 metabolites were all present in rat bile, while only 9 were detected in plasma. O-demethylation, hydroxylation, di-hydroxylation, glucuronidation of O-demethyl DHC, sulfation of O-demethyl DHC and di-hydroxylation of dehydro-DHC were the major metabolic pathways of DHC. This is the first time that these metabolites of DHC have been identified in rat plasma and bile, which provides useful information for further analysis of the biotransformation of DHC and other quaternary protoberberine-type alkaloids. Full article
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Article
Inositol Hexaphosphate Inhibits Proliferation and Induces Apoptosis of Colon Cancer Cells by Suppressing the AKT/mTOR Signaling Pathway
by Małgorzata Kapral, Joanna Wawszczyk, Katarzyna Jesse, Monika Paul-Samojedny, Dariusz Kuśmierz and Ludmiła Węglarz
Molecules 2017, 22(10), 1657; https://doi.org/10.3390/molecules22101657 - 03 Oct 2017
Cited by 29 | Viewed by 6231
Abstract
Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as [...] Read more.
Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as an attractive target for anticancer therapy. Inositol hexaphosphate (InsP6), a natural occurring phytochemical, has been shown to have both preventive and therapeutic effects against various cancers, however, its exact molecular mechanisms of action are not fully understood. The aim of the in vitro study was to investigate the anticancer activity of InsP6 on colon cancer with the focus on inhibiting the AKT1 kinase and p70S6K1 as mTOR effector, in relation to proliferation and apoptosis of cells. The colon cancer Caco-2 cells were cultured using standard techniques and exposed to InsP6 at different concentrations (1 mM, 2.5 mM and 5 mM). Cellular proliferative activity was monitored by 5-bromo-2′-deoxyuridine (BrdU) incorporation into cellular DNA. Flow cytometric analysis was performed for cell cycle progression and apoptosis studies. Real-time RT-qPCR was used to validate mRNA levels of CDNK1A, CDNK1B, CASP3, CASP9, AKT1 and S6K1 genes. The concentration of p21 protein as well as the activities of caspase 3, AKT1 and p70S6K1 were determined by the ELISA method. The results revealed that IP6 inhibited proliferation and stimulated apoptosis of colon cancer cells. This effect was mediated by an increase in the expression of genes encoding p21, p27, caspase 3, caspase 9 as well a decrease in transcription of AKT1 and S6K1. InsP6 suppressed phosphorylation of AKT1 and p70S6K1, downstream effector of mTOR. Based on these studies it may be concluded that InsP6 can reduce proliferation and induce apoptosis through inhibition of the AKT/mTOR pathway and mTOR effector followed by modulation of the expression and activity of several key components of these pathways in colon cancer cells. Full article
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Article
A Network Pharmacology-Based Study on the Hepatoprotective Effect of Fructus Schisandrae
by Ming Hong, Yongsheng Zhang, Sha Li, Hor Yue Tan, Ning Wang, Shuzhen Mu, Xiaojiang Hao and Yibin Feng
Molecules 2017, 22(10), 1617; https://doi.org/10.3390/molecules22101617 - 28 Sep 2017
Cited by 43 | Viewed by 8541
Abstract
Fructus schisandrae (Wuweizi in Chinese), a common traditional Chinese herbal medicine, has been used for centuries to treat chronic liver disease. The therapeutic efficacy of Wuweizi has also been validated in clinical practice. In this study, molecular docking and network analysis were carried [...] Read more.
Fructus schisandrae (Wuweizi in Chinese), a common traditional Chinese herbal medicine, has been used for centuries to treat chronic liver disease. The therapeutic efficacy of Wuweizi has also been validated in clinical practice. In this study, molecular docking and network analysis were carried out to explore the hepatoprotective mechanism of Wuweizi as an effective therapeutic approach to treat liver disease. Multiple active compounds of Wuweizi were docked with 44 protein targets related with viral hepatitis, fatty liver, liver fibrosis, cirrhosis, and liver cancer. A compound–target network was constructed through network pharmacology analysis, predicting the relationships of active ingredients to the targets. Our results demonstrated that schisantherin, schisandrin B, schisandrol B, kadsurin, Wuweizisu C, Gomisin A, Gomisin G, and angeloylgomisin may target with 21 intracellular proteins associated with liver diseases, especially with fatty liver disease. The CYP2E1, PPARα, and AMPK genes and their related pathway may play a pivotal role in the hepatoprotective effects of Wuweizi. The network pharmacology strategy used provides a forceful tool for searching the action mechanism of traditional herbal medicines and novel bioactive ingredients. Full article
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Review
A Phytochemical-Sensing Strategy Based on Mass Spectrometry Imaging and Metabolic Profiling for Understanding the Functionality of the Medicinal Herb Green Tea
by Yoshinori Fujimura, Daisuke Miura and Hirofumi Tachibana
Molecules 2017, 22(10), 1621; https://doi.org/10.3390/molecules22101621 - 27 Sep 2017
Cited by 10 | Viewed by 8830
Abstract
Low-molecular-weight phytochemicals have health benefits and reduce the risk of diseases, but the mechanisms underlying their activities have remained elusive because of the lack of a methodology that can easily visualize the exact behavior of such small molecules. Recently, we developed an in [...] Read more.
Low-molecular-weight phytochemicals have health benefits and reduce the risk of diseases, but the mechanisms underlying their activities have remained elusive because of the lack of a methodology that can easily visualize the exact behavior of such small molecules. Recently, we developed an in situ label-free imaging technique, called mass spectrometry imaging, for visualizing spatially-resolved biotransformations based on simultaneous mapping of the major bioactive green tea polyphenol and its phase II metabolites. In addition, we established a mass spectrometry-based metabolic profiling technique capable of evaluating the bioactivities of diverse green tea extracts, which contain multiple phytochemicals, by focusing on their compositional balances. This methodology allowed us to simultaneously evaluate the relative contributions of the multiple compounds present in a multicomponent system to its bioactivity. This review highlights small molecule-sensing techniques for visualizing the complex behaviors of herbal components and linking such information to an enhanced understanding of the functionalities of multicomponent medicinal herbs. Full article
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Review
Diverse Phytochemicals and Bioactivities in the Ancient Fruit and Modern Functional Food Pomegranate (Punica granatum)
by Sheng Wu and Li Tian
Molecules 2017, 22(10), 1606; https://doi.org/10.3390/molecules22101606 - 25 Sep 2017
Cited by 138 | Viewed by 12085
Abstract
Having served as a symbolic fruit since ancient times, pomegranate (Punica granatum) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), [...] Read more.
Having served as a symbolic fruit since ancient times, pomegranate (Punica granatum) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), to the health-promoting activities of pomegranate juice and fruit extracts. However, it remains unclear as to how, and to what extent, the numerous phytochemicals in pomegranate may interact and exert cooperative activities in humans. In this review, we examine the structural and analytical information of the diverse phytochemicals that have been identified in different pomegranate tissues, to establish a knowledge base for characterization of metabolite profiles, discovery of novel phytochemicals, and investigation of phytochemical interactions in pomegranate. We also assess recent findings on the function and molecular mechanism of ATs as well as urolithins, the intestinal microbial derivatives of pomegranate HTs, on human nutrition and health. A better understanding of the structural diversity of pomegranate phytochemicals as well as their bioconversions and bioactivities in humans will facilitate the interrogation of their synergistic/antagonistic interactions and accelerate their applications in dietary-based cancer chemoprevention and treatment in the future. Full article
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Article
Aspalathin Reverts Doxorubicin-Induced Cardiotoxicity through Increased Autophagy and Decreased Expression of p53/mTOR/p62 Signaling
by Rabia Johnson, Samukelisiwe Shabalala, Johan Louw, Abidemi Paul Kappo and Christo John Frederick Muller
Molecules 2017, 22(10), 1589; https://doi.org/10.3390/molecules22101589 - 22 Sep 2017
Cited by 45 | Viewed by 7733
Abstract
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 [...] Read more.
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco’s Modified Eagle’s medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2 µM Dox were co-treated with either 20 µM Dexrazozane (Dexra) or 0.2 µM aspalathin (ASP) daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs) with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity. Full article
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Article
Anti-Inflammatory and Anti-Oxidative Activities of Phenolic Compounds from Alnus sibirica Stems Fermented by Lactobacillus plantarum subsp. argentoratensis
by Thi Tam Le, Jun Yin and MinWon Lee
Molecules 2017, 22(9), 1566; https://doi.org/10.3390/molecules22091566 - 18 Sep 2017
Cited by 11 | Viewed by 5121
Abstract
Fermentation of Alnus sibirica (AS) stems using Lactobacillus plantarum subsp. argentoratensis was conducted and three compounds isolated from the Alnus species were identified for the first time, 7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-heptan-3-one, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3-one and 4-(3,4-dihydroxyphenyl)-butan-2-one, along with 14 known compounds. The anti-oxidative and anti-inflammatory abilities of AS [...] Read more.
Fermentation of Alnus sibirica (AS) stems using Lactobacillus plantarum subsp. argentoratensis was conducted and three compounds isolated from the Alnus species were identified for the first time, 7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-heptan-3-one, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3-one and 4-(3,4-dihydroxyphenyl)-butan-2-one, along with 14 known compounds. The anti-oxidative and anti-inflammatory abilities of AS and fermented AS (FAS) as well as the isolated phenolic compounds from FAS were investigated. FAS showed stronger anti-oxidative and anti-inflammatory activities than non-fermented AS. Full article
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Article
Comparison of Two Components of Propolis: Caffeic Acid (CA) and Caffeic Acid Phenethyl Ester (CAPE) Induce Apoptosis and Cell Cycle Arrest of Breast Cancer Cells MDA-MB-231
by Agata Kabała-Dzik, Anna Rzepecka-Stojko, Robert Kubina, Żaneta Jastrzębska-Stojko, Rafał Stojko, Robert Dariusz Wojtyczka and Jerzy Stojko
Molecules 2017, 22(9), 1554; https://doi.org/10.3390/molecules22091554 - 15 Sep 2017
Cited by 66 | Viewed by 8348
Abstract
Studies show that caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common form of aggressive cancer among women worldwide. This study shows a comparison of CA and CAPE activity on triple-negative human [...] Read more.
Studies show that caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common form of aggressive cancer among women worldwide. This study shows a comparison of CA and CAPE activity on triple-negative human caucasian breast adenocarcinoma line cells (MDA-MB-231). MDA-MB-231 cells were treated by CA and CAPE with doses of from 10 to 100 µM, for periods of 24 h and 48 h. Cytotoxicity MTT tests, apoptosis by Annexin V, and cell cycle with Dead Cell Assays were performed. Cytotoxic activity was greater for CAPE compared to CA (both incubation times, same dosage). IC50 values for CAPE were 27.84 µM (24 h) and 15.83 µM (48 h) and for CA > 10,000 µM (24 h) and > 1000 µM (48 h). Polyphenols induced apoptosis, while CAPE (dose dependently), induced a higher apoptotic effect. CAPE also induced cell cycle arrest in S phase (time and dose dependently), CA did it only for 50 and 100 µM. A dose dependent decline was seen for the G0/G1 phase (CAPE, 48 h), as well as elimination of phase G2/M by 100 µM of CAPE (only mild effect for CA). Comparing CA and CAPE activity on MDA-MB-231, CAPE clearly showed better activity for the same dosages and experiment times. Full article
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Article
An NMR-Based Metabolomic Approach to Unravel the Preventive Effect of Water-Soluble Extract from Dendrobium officinale Kimura & Migo on Streptozotocin-Induced Diabetes in Mice
by Hong Zheng, Linlin Pan, Pengtao Xu, Jianjun Zhu, Ruohan Wang, Wenzong Zhu, Yongsheng Hu and Hongchang Gao
Molecules 2017, 22(9), 1543; https://doi.org/10.3390/molecules22091543 - 15 Sep 2017
Cited by 24 | Viewed by 5163
Abstract
Dendrobium officinale Kimura & Migo (D. officinale) is a precious herbal medicine. In this study, we investigated metabolic mechanism underlying the effect of D. officinale water extract (DOWE) on diabetes prevention in mice after streptozotocin (STZ) exposure using NMR-based metabolomics. Interestingly, [...] Read more.
Dendrobium officinale Kimura & Migo (D. officinale) is a precious herbal medicine. In this study, we investigated metabolic mechanism underlying the effect of D. officinale water extract (DOWE) on diabetes prevention in mice after streptozotocin (STZ) exposure using NMR-based metabolomics. Interestingly, we found a decrease in blood glucose and an increase in liver glycogen in mice pretreated with DOWE after STZ exposure. The DOWE pretreatment significantly increased citrate and glutamine in the serum as well as creatine, alanine, leucine, isoleucine, valine, glutamine, glutathione and taurine in the liver of STZ-treated mice. Furthermore, serum glucose was significantly negatively correlated with citrate, pyruvate, alanine, isoleucine, histidine and glutamine in the serum as well as alanine and taurine in the liver. These findings suggest that the effect of DOWE on diabetes prevention may be linked to increases in liver glycogen and taurine as well as the up-regulation of energy and amino acid metabolism. Full article
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Article
Senna singueana: Antioxidant, Hepatoprotective, Antiapoptotic Properties and Phytochemical Profiling of a Methanol Bark Extract
by Mansour Sobeh, Mona F. Mahmoud, Rehab A. Hasan, Haroan Cheng, Assem M. El-Shazly and Michael Wink
Molecules 2017, 22(9), 1502; https://doi.org/10.3390/molecules22091502 - 08 Sep 2017
Cited by 41 | Viewed by 7499
Abstract
Natural products are considered as an important source for the discovery of new drugs to treat aging-related degenerative diseases and liver injury. The present study profiled the chemical constituents of a methanol extract from Senna singueana bark using HPLC-PDA-ESI-MS/MS and 36 secondary metabolites [...] Read more.
Natural products are considered as an important source for the discovery of new drugs to treat aging-related degenerative diseases and liver injury. The present study profiled the chemical constituents of a methanol extract from Senna singueana bark using HPLC-PDA-ESI-MS/MS and 36 secondary metabolites were identified. Proanthocyanidins dominated the extract. Monomers, dimers, trimers of (epi)catechin, (epi)gallocatechin, (epi)guibourtinidol, (ent)cassiaflavan, and (epi)afzelechin represented the major constituents. The extract demonstrated notable antioxidant activities in vitro: In DPPH (EC50 of 20.8 µg/mL), FRAP (18.16 mM FeSO4/mg extract) assays, and total phenolic content amounted 474 mg gallic acid equivalent (GAE)/g extract determined with the Folin-Ciocalteu method. Also, in an in vivo model, the extract increased the survival rate of Caenorhabditis elegans worms pretreated with the pro-oxidant juglone from 43 to 64%, decreased intracellular ROS inside the wild-type nematodes by 47.90%, and induced nuclear translocation of the transcription factor DAF-16 in the transgenic strain TJ356. Additionally, the extract showed a remarkable hepatoprotective activity against d-galactosamine (d-GalN) induced hepatic injury in rats. It significantly reduced elevated AST (aspartate aminotransferase), and total bilirubin. Moreover, the extract induced a strong cytoplasmic Bcl-2 expression indicating suppression of apoptosis. In conclusion, the bark extract of S. sengueana represents an interesting candidate for further research in antioxidants and liver protection. Full article
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Review
Ethnopharmacology and Therapeutic Value of Bridelia micrantha (Hochst.) Baill. in Tropical Africa: A Comprehensive Review
by Alfred Maroyi
Molecules 2017, 22(9), 1493; https://doi.org/10.3390/molecules22091493 - 08 Sep 2017
Cited by 20 | Viewed by 6559
Abstract
Bridelia micrantha is traditionally used in tropical Africa to treat a wide range of human and animal diseases. The aim of this study was to summarise the research that has been done on the ethnomedicinal uses, phytochemistry and pharmacological properties of B. micrantha [...] Read more.
Bridelia micrantha is traditionally used in tropical Africa to treat a wide range of human and animal diseases. The aim of this study was to summarise the research that has been done on the ethnomedicinal uses, phytochemistry and pharmacological properties of B. micrantha so as to understand its importance and potential value in primary healthcare systems. The literature search for information on ethnomedicinal uses and pharmacological activities of B. micrantha was undertaken using databases such as Web of Science, Scopus, Google Scholar, Science Direct, BioMed Central (BMC), PubMed and Springerlink. Other relevant literature sources included books, book chapters, websites, theses, conference papers and other scientific publications. This study showed that B. micrantha is used as herbal medicine in just over half (57.3%) of the countries in tropical Africa where it is indigenous. A total of 54 ethnomedicinal uses of B. micrantha have been recorded with a high degree of consensus on burns, wounds, conjunctivitis, painful eyes, constipation, gastric ulcers, cough, headache, rheumatism, painful joints, dysentery, ethnoveterinary medicine, malaria, sexually transmitted infections, stomach ache, tape worms and diarrhoea. Different plant parts, aqueous and organic extracts exhibited anthelmintic, antimicrobial, anticonvulsant and sedative, antidiabetic, antidiarrhoeal, antinociceptive, antioxidant, antiplasmodial, antischistosomal, hepatoprotective, insecticidal and β-lactamase inhibitory activities. Full article
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Review
Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety
by Beibei Chen, Lili Wang, Lin Li, Ruyuan Zhu, Haixia Liu, Chenyue Liu, Rufeng Ma, Qiangqiang Jia, Dandan Zhao, Jianzhao Niu, Min Fu, Sihua Gao and Dongwei Zhang
Molecules 2017, 22(9), 1469; https://doi.org/10.3390/molecules22091469 - 05 Sep 2017
Cited by 53 | Viewed by 9107
Abstract
Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, [...] Read more.
Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)2D3/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety. Full article
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Article
Germination under Moderate Salinity Increases Phenolic Content and Antioxidant Activity in Rapeseed (Brassica napus var oleifera Del.) Sprouts
by Beatrice Falcinelli, Valeria Sileoni, Ombretta Marconi, Giuseppe Perretti, Muriel Quinet, Stanley Lutts and Paolo Benincasa
Molecules 2017, 22(8), 1377; https://doi.org/10.3390/molecules22081377 - 19 Aug 2017
Cited by 47 | Viewed by 5550
Abstract
The use of sprouts in the human diet is becoming more and more widespread because they are tasty and high in bioactive compounds and antioxidants, with related health benefits. In this work, we sprouted rapeseed under increasing salinity to investigate the effect on [...] Read more.
The use of sprouts in the human diet is becoming more and more widespread because they are tasty and high in bioactive compounds and antioxidants, with related health benefits. In this work, we sprouted rapeseed under increasing salinity to investigate the effect on free and bound total phenolics (TP), non-flavonoids (NF), tannins (TAN), phenolic acids (PAs), and antioxidant activity. Seeds were incubated at 0, 25, 50, 100, 200 mM NaCl until early or late sprout stage, i.e., before or after cotyledon expansion, respectively. Sprouting and increasing salinity slightly decreased the bound fractions of TP, NF, TAN, PAs, while it increased markedly the free ones and their antioxidant activity. Further increases were observed in late sprouts. Moderate salinity (25–50 mM NaCl) caused the highest relative increase in phenolic concentration while it slightly affected sprout growth. On the contrary, at higher NaCl concentrations, sprouts grew slowly (100 mM NaCl) or even died before reaching the late sprout stage (200 mM). Overall, moderate salinity was the best compromise to increase phenolic content of rapeseed sprouts. The technique may be evaluated for transfer to other species as a cheap and feasible way to increase the nutritional value of sprouts. Full article
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1897 KiB  
Article
Spirulina maxima Extract Prevents Neurotoxicity via Promoting Activation of BDNF/CREB Signaling Pathways in Neuronal Cells and Mice
by Eun-Jeong Koh, Young-Jin Seo, Jia Choi, Hyeon Yong Lee, Do-Hyung Kang, Kui-Jin Kim and Boo-Yong Lee
Molecules 2017, 22(8), 1363; https://doi.org/10.3390/molecules22081363 - 17 Aug 2017
Cited by 30 | Viewed by 7309
Abstract
Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin [...] Read more.
Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin (TMT)-induced neurotoxicity in HT-22 cells. SM70EE inhibited the cleavage of poly-ADP ribose polymerase (PARP). Besides, ROS production was decreased by down-regulating oxidative stress-associated enzymes. SM70EE increased the factors of brain-derived neurotrophic factor (BDNF)/cyclic AMPresponsive elementbinding protein (CREB) signalling pathways. Additionally, acetylcholinesterase (AChE) was suppressed by SM70EE. Furthermore, we investigated whether SM70EE prevents cognitive deficits against scopolamine-induced neurotoxicity in mice by applying behavioral tests. SM70EE increased step-through latency time and decreased the escape latency time. Therefore, our data suggest that SM70EE may prevent TMT neurotoxicity through promoting activation of BDNF/CREB neuroprotective signaling pathways in neuronal cells. In vivo study, SM70EE would prevent cognitive deficits against scopolamine-induced neurotoxicity in mice. Full article
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3469 KiB  
Article
Phosphate-Linked Silibinin Dimers (PLSd): New Promising Modified Metabolites
by Valeria Romanucci, Raffaele Gravante, Martina Cimafonte, Cinzia Di Marino, Gilles Mailhot, Marcello Brigante, Armando Zarrelli and Giovanni Di Fabio
Molecules 2017, 22(8), 1323; https://doi.org/10.3390/molecules22081323 - 11 Aug 2017
Cited by 21 | Viewed by 4400
Abstract
By exploiting the regioselective protection of the hydroxyl groups of silibinin along with the well-known phosphoramidite chemistry, we have developed an efficient strategy for the synthesis of new silibinin-modified species, which we have named Phosphate-Linked Silibinin Dimers (PLSd), in which the monomer units [...] Read more.
By exploiting the regioselective protection of the hydroxyl groups of silibinin along with the well-known phosphoramidite chemistry, we have developed an efficient strategy for the synthesis of new silibinin-modified species, which we have named Phosphate-Linked Silibinin Dimers (PLSd), in which the monomer units are linked by phosphodiester bonds. The antioxidant abilities of the new PLSd were estimated on HepG2 cells using DPPH free radical scavenging and xanthine/xanthine oxidase assays. The new phosphate-metabolites showed a higher anti-oxidant activity than the silibinin, as well as very low toxicity. The ability to scavenge reactive oxygen species (ROS) such as singlet oxygen () and hydroxyl radical () reveals that the two dimers are able to scavenge about two times more effectively than silibinin. Finally, solubility studies have shown that the PLSd present good water solubility (more than 20 mg·L−1) under circumneutral pH values, whereas the silibinin was found to be very poorly soluble (less than 0.4 mg·L−1) and not stable under alkaline conditions. Together, the above promising results warrant further investigation of the future potential of the PLSd as anti-oxidant metabolites within the large synthetic polyphenols field. Full article
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2111 KiB  
Article
Five New Phenolic Compounds with Antioxidant Activities from the Medicinal Insect Blaps rynchopetera
by Huai Xiao, Tian-Peng Yin, Jian-Wei Dong, Xiu-Mei Wu, Qing Luo, Jian-Rong Luo, Le Cai and Zhong-Tao Ding
Molecules 2017, 22(8), 1301; https://doi.org/10.3390/molecules22081301 - 04 Aug 2017
Cited by 22 | Viewed by 4725
Abstract
Five new phenolic compounds rynchopeterines A–E (15), in addition to thirteen known phenolics, were isolated from Blaps rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi Nationality in Yunnan Province of China. Their structures were established on [...] Read more.
Five new phenolic compounds rynchopeterines A–E (15), in addition to thirteen known phenolics, were isolated from Blaps rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS, IR) along with calculated electronic circular dichroism method. Rynchopeterines A–E (14) exhibited significant antioxidant activities with IC50 values of 7.67–12.3 μg/mL measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Besides, rynchopeterines B (2) and C (3) showed mild cytotoxicity against tumor cell Caco-2 and A549. Full article
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Article
Evaluation of the Nutritional Quality of Chinese Kale (Brassica alboglabra Bailey) Using UHPLC-Quadrupole-Orbitrap MS/MS-Based Metabolomics
by Ya-Qin Wang, Li-Ping Hu, Guang-Min Liu, De-Shuang Zhang and Hong-Ju He
Molecules 2017, 22(8), 1262; https://doi.org/10.3390/molecules22081262 - 27 Jul 2017
Cited by 38 | Viewed by 5797
Abstract
Chinese kale (Brassica alboglabra Bailey) is a widely consumed vegetable which is rich in antioxidants and anticarcinogenic compounds. Herein, we used an untargeted ultra-high-performance liquid chromatography (UHPLC)-Quadrupole-Orbitrap MS/MS-based metabolomics strategy to study the nutrient profiles of Chinese kale. Seven Chinese kale cultivars [...] Read more.
Chinese kale (Brassica alboglabra Bailey) is a widely consumed vegetable which is rich in antioxidants and anticarcinogenic compounds. Herein, we used an untargeted ultra-high-performance liquid chromatography (UHPLC)-Quadrupole-Orbitrap MS/MS-based metabolomics strategy to study the nutrient profiles of Chinese kale. Seven Chinese kale cultivars and three different edible parts were evaluated, and amino acids, sugars, organic acids, glucosinolates and phenolic compounds were analysed simultaneously. We found that two cultivars, a purple-stem cultivar W1 and a yellow-flower cultivar Y1, had more health-promoting compounds than others. The multivariate statistical analysis results showed that gluconapin was the most important contributor for discriminating both cultivars and edible parts. The purple-stem cultivar W1 had higher levels of some phenolic acids and flavonoids than the green stem cultivars. Compared to stems and leaves, the inflorescences contained more amino acids, glucosinolates and most of the phenolic acids. Meanwhile, the stems had the least amounts of phenolic compounds among the organs tested. Metabolomics is a powerful approach for the comprehensive understanding of vegetable nutritional quality. The results provide the basis for future metabolomics-guided breeding and nutritional quality improvement. Full article
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1997 KiB  
Article
Anthocyanin Profiles in Flowers of Grape Hyacinth
by Qian Lou, Lin Wang, Hongli Liu and Yali Liu
Molecules 2017, 22(5), 688; https://doi.org/10.3390/molecules22050688 - 26 Apr 2017
Cited by 24 | Viewed by 7680
Abstract
Grape hyacinth (Muscari spp.) is a popular ornamental bulbous perennial famous for its blue flowers. To understand the chemical basis of the rich blue colors in this plant, anthocyanin profiles of six blue flowering grape hyacinths as well as one pink and [...] Read more.
Grape hyacinth (Muscari spp.) is a popular ornamental bulbous perennial famous for its blue flowers. To understand the chemical basis of the rich blue colors in this plant, anthocyanin profiles of six blue flowering grape hyacinths as well as one pink and one white cultivar were determined using high-performance liquid chromatography and mass spectrometry. Along with two known compounds, eight putative anthocyanins were identified in the tepals of grape hyacinth for the first time. The accumulation and distribution of anthocyanins in the plant showed significant cultivar and flower development specificity. Violet-blue flowers mainly contained simple delphinidin-type anthocyanins bearing one or two methyl-groups but no acyl groups, whereas white and pink flowers synthesised more complex pelargonidin/cyanidin-derivatives with acyl-moieties but no methyl-groups. The results partially reveal why solid blue, orange or red flowers are rare in this plant in nature. In addition, pelargonidin-type anthocyanins were found for the first time in the genus, bringing more opportunities in terms of breeding of flower color in grape hyacinth. Full article
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3885 KiB  
Article
Diversity Analysis and Bioresource Characterization of Halophilic Bacteria Isolated from a South African Saltpan
by Ramganesh Selvarajan, Timothy Sibanda, Memory Tekere, Hlengilizwe Nyoni and Stephen Meddows-Taylor
Molecules 2017, 22(4), 657; https://doi.org/10.3390/molecules22040657 - 20 Apr 2017
Cited by 34 | Viewed by 8624
Abstract
Though intensive research has been channeled towards the biotechnological applications of halophiles and other extremophilic microbes, these studies have not been, by any means, exhaustive. Saline environments still offer a vast diversity of microbes with potential to produce an array of natural products [...] Read more.
Though intensive research has been channeled towards the biotechnological applications of halophiles and other extremophilic microbes, these studies have not been, by any means, exhaustive. Saline environments still offer a vast diversity of microbes with potential to produce an array of natural products which can only be unlocked by concerted research efforts. In this study, a combination of culture and molecular approaches were employed to characterize halophilic bacteria from saltpan water samples and profile their potential biotechnological applications. Physicochemical analysis of the water samples showed that pH was alkaline (pH 8.8), with a salinity of 12.8%. 16S rRNA gene targeted amplicon analysis produced 10 bacterial phyla constituting of Bacteroidetes (30.57%), Proteobacteria (15.27%), Actinobacteria (9.05%), Planctomycetes (5.52%) and Cyanobacteria (3.18%). Eighteen strains were identified using sequencing analysis of the culturable bacterial strains. From these, the strains SP7 and SP9 were positive for cellulase production while the strains SP4, SP8 and SP22 were positive for lipase production. Quantitative enzyme assays showed moderate extracellular cellulase activity (1.95 U/mL) and lipase activity (3.71 U/mL) by the isolate SP9 and SP4 respectively. Further, of the six isolates, the isolate SP9 exhibited exploitable potential in the bioremediation of hydrocarbon pollution as demonstrated by its fairly high activity against benzanthracene (70% DCPIP reduction). Elucidation of the isolates secondary metabolites showed the production of the molecules 2,3-butanediol, hexahydro-3-(2-methylpropyl)pyrrole[1,2a]pyrazine-1,4-dione, aziridine, dimethylamine and ethyl acetate (GC-MS) and oxypurinol and 5-hydroxydecanoic acid (LC-MS), particularly by the isolate Salinivibrio sp. SP9. Overall, the study showed that the isolated halophiles can produce secondary metabolites with potential industrial and pharmaceutical application. Full article
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6186 KiB  
Article
Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
by Aihua Huang, Hui Xu, Ruoting Zhan, Weiwen Chen, Jiawei Liu, Yuguang Chi, Daidi Chen, Xiaoyu Ji and Chaoquan Luo
Molecules 2017, 22(4), 489; https://doi.org/10.3390/molecules22040489 - 23 Mar 2017
Cited by 18 | Viewed by 5068
Abstract
Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite [...] Read more.
Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite profiling of skimmianine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilotTM software. These predicted metabolites were further analyzed by MS2 spectra, and compared with the detailed fragmentation pathway of the skimmianine standard and literature data. A total of 16 metabolites were identified for the first time in rat plasma, urine, and feces samples after oral administration of skimmianine. Skimmianine underwent extensive Phase I and Phase II metabolism in rats. The Phase I biotransformations of skimmianine consist of epoxidation of olefin on its furan ring (M1) followed by the hydrolysis of the epoxide ring (M4), hydroxylation (M2, M3), O-demethylation (M5-M7), didemethylation (M14–M16). The Phase II biotransformations include glucuronide conjugation (M8–M10) and sulfate conjugation (M11–M13). The epoxidation of 2,3-olefinic bond followed by the hydrolysis of the epoxide ring and O-demethylation were the major metabolic pathways of skimmianine. The results provide key information for understanding the biotransformation processes of skimmianine and the related furoquinoline alkaloids. Full article
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1108 KiB  
Article
Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity
by Yosuke Matsubara, Takashi Matsumoto, Kyoji Sekiguchi, Junichi Koseki, Atsushi Kaneko, Takuji Yamaguchi, Yumiko Kurihara and Hiroyuki Kobayashi
Molecules 2017, 22(2), 256; https://doi.org/10.3390/molecules22020256 - 08 Feb 2017
Cited by 14 | Viewed by 7515
Abstract
Insufficient detoxification and/or overproduction of reactive oxygen species (ROS) induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY) is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to [...] Read more.
Insufficient detoxification and/or overproduction of reactive oxygen species (ROS) induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY) is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs) in plasma. ROS-scavenging and lipid hydroperoxide (LPO) generation assays revealed that gallic acid, 3-O-methylgallic acid, (+)-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases. Full article
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Article
Toxicity of Plant Secondary Metabolites Modulating Detoxification Genes Expression for Natural Red Palm Weevil Pesticide Development
by Ahmed Mohammed AlJabr, Abid Hussain, Muhammad Rizwan-ul-Haq and Hassan Al-Ayedh
Molecules 2017, 22(1), 169; https://doi.org/10.3390/molecules22010169 - 20 Jan 2017
Cited by 49 | Viewed by 6844
Abstract
This study aimed to explore the larvicidal and growth-inhibiting activities, and underlying detoxification mechanism of red palm weevil against phenylpropanoids, an important class of plant secondary metabolites. Toxicity of α-asarone, eugenol, isoeugenol, methyl eugenol, methyl isoeugenol, coumarin, coumarin 6, coniferyl aldehyde, diniconazole, ethyl [...] Read more.
This study aimed to explore the larvicidal and growth-inhibiting activities, and underlying detoxification mechanism of red palm weevil against phenylpropanoids, an important class of plant secondary metabolites. Toxicity of α-asarone, eugenol, isoeugenol, methyl eugenol, methyl isoeugenol, coumarin, coumarin 6, coniferyl aldehyde, diniconazole, ethyl cinnamate, and rosmarinic acid was evaluated by incorporation into the artificial diet. All of the phenylpropanoids exhibited dose- and time-dependent insecticidal activity. Among all the tested phenylpropanoids, coumarin exhibited the highest toxicity by revealing the least LD50 value (0.672 g/L). In addition, the most toxic compound (coumarin) observed in the current study, deteriorated the growth resulting tremendous reduction (78.39%) in efficacy of conversion of digested food (ECD), and (ECI) efficacy of conversion of ingested food (70.04%) of tenth-instar red palm weevil larvae. The energy-deficient red palm weevil larvae through their intrinsic abilities showed enhanced response to their digestibility resulting 27.78% increase in approximate digestibility (AD) compared to control larvae. The detoxification response of Rhynchophorus ferrugineus larvae determined by the quantitative expression of cytochrome P450, esterases, and glutathione S-transferase revealed enhanced expression among moderately toxic and ineffective compounds. These genes especially cytochrome P450 and GST detoxify the target compounds by enhancing their solubility that leads rapid excretion and degradation resulting low toxicity towards red palm weevil larvae. On the other hand, the most toxic (coumarin) silenced the genes involved in the red palm weevil detoxification mechanism. Based on the toxicity, growth retarding, and masking detoxification activities, coumarin could be a useful future natural red palm weevil-controlling agent. Full article
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2016

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1534 KiB  
Article
Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti
by Haonan Zhou, Pengjie Zhang, Zhiguo Hou, Jiabin Xie, Yuming Wang, Bin Yang, Yanyan Xu and Yubo Li
Molecules 2016, 21(12), 1623; https://doi.org/10.3390/molecules21121623 - 25 Nov 2016
Cited by 16 | Viewed by 6095
Abstract
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, [...] Read more.
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity. Full article
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1189 KiB  
Article
Chemical Constituents from the Aerial Parts of Cyrtopodium paniculatum
by Florence Auberon, Opeyemi Joshua Olatunji, Gaëtan Herbette, Diamondra Raminoson, Cyril Antheaume, Beatriz Soengas, Frédéric Bonté and Annelise Lobstein
Molecules 2016, 21(10), 1418; https://doi.org/10.3390/molecules21101418 - 24 Oct 2016
Cited by 12 | Viewed by 5803
Abstract
We report the first phytochemical study of the neotropical orchid Cyrtopodium paniculatum. Eight new compounds, including one phenanthrene 1, one 9,10-dihydro-phenanthrene 2, one hydroxybenzylphenanthrene 3, two biphenanthrenes 45, and three 9,10 dihydrophenanthrofurans 68, [...] Read more.
We report the first phytochemical study of the neotropical orchid Cyrtopodium paniculatum. Eight new compounds, including one phenanthrene 1, one 9,10-dihydro-phenanthrene 2, one hydroxybenzylphenanthrene 3, two biphenanthrenes 45, and three 9,10 dihydrophenanthrofurans 68, together with 28 known phenolic compounds, mostly stilbenoids, were isolated from the CH2Cl2 extract of its leaves and pseudobulbs. The structures of the new compounds were established on the basis of extensive spectroscopic methods. Full article
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2238 KiB  
Article
Icariin Metabolism by Human Intestinal Microflora
by Hailong Wu, Mihyang Kim and Jaehong Han
Molecules 2016, 21(9), 1158; https://doi.org/10.3390/molecules21091158 - 31 Aug 2016
Cited by 56 | Viewed by 7308
Abstract
Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information [...] Read more.
Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information for the study of the icaritin metabolism, the biotransformation of icariin by the human intestinal bacteria is reported for the first time. Together with human intestinal microflora, the three bacteria Streptococcus sp. MRG-ICA-B, Enterococcus sp. MRG-ICA-E, and Blautia sp. MRG-PMF-1 isolated from human intestine were reacted with icariin under anaerobic conditions. The metabolites including icariside II, icaritin, and desmethylicaritin, but not icariside I, were produced. The MRG-ICA-B and E strains hydrolyzed only the glucose moiety of icariin, and icariside II was the only metabolite. However, the MRG-PMF-1 strain metabolized icariin further to desmethylicaritin via icariside II and icaritin. From the results, along with the icariin metabolism by human microflora, it was evident that most icariin is quickly transformed to icariside II before absorption in the human intestine. We propose the pharmacokinetics of icariin should focus on metabolites such as icariside II, icaritin and desmethylicaritin to explain the discrepancy between the in vitro bioassay and pharmacological effects. Full article
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1382 KiB  
Article
In Vivo Metabolite Profiling of a Purified Ellagitannin Isolated from Polygonum capitatum in Rats
by Jing-Yi Ma, Xuelin Zhou, Jie Fu, Chi-Yu He, Ru Feng, Min Huang, Jia-Wen Shou, Zhen-Xiong Zhao, Xiao-Yang Li, Luye Zhang, Yang-Chao Chen and Yan Wang
Molecules 2016, 21(9), 1110; https://doi.org/10.3390/molecules21091110 - 24 Aug 2016
Cited by 13 | Viewed by 5461
Abstract
Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to [...] Read more.
Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to investigate the metabolic profiles of FR429 in rats in vivo. Using liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MSn-IT-TOF), total eight metabolites were found in rat bile and urine after intravenous administration of FR429, but could not be detected in plasma. These metabolites were ellagic acid, mono-methylated FR429, ellagic acid methyl ether glucuronide, ellagic acid methyl ether diglucuronide, ellagic acid dimethyl ether glucuronide, and ellagic acid dimethyl ether diglucuronide. It was concluded that methylation and subsequent glucuronidation were the major metabolic pathways of FR429 in rats in vivo. This is the first report on the in vivo metabolism of the purified ellagitannin in rats. Full article
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1506 KiB  
Article
Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation
by Shafiq Ur Rahman, Achyut Adhikari, Muhammad Ismail, Muhammad Raza Shah, Muhammad Khurram, Muhammad Shahid, Farman Ali, Abdul Haseeb, Fazal Akbar and Marcello Iriti
Molecules 2016, 21(8), 1095; https://doi.org/10.3390/molecules21081095 - 20 Aug 2016
Cited by 22 | Viewed by 8021
Abstract
Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity [...] Read more.
Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation. Full article
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1033 KiB  
Review
Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks
by João P. Monteiro, Marco G. Alves, Pedro F. Oliveira and Branca M. Silva
Molecules 2016, 21(8), 974; https://doi.org/10.3390/molecules21080974 - 27 Jul 2016
Cited by 102 | Viewed by 15910
Abstract
Methylxanthines are a group of phytochemicals derived from the purine base xanthine and obtained from plant secondary metabolism. They are unobtrusively included in daily diet in common products as coffee, tea, energetic drinks, or chocolate. Caffeine is by far the most studied methylxanthine [...] Read more.
Methylxanthines are a group of phytochemicals derived from the purine base xanthine and obtained from plant secondary metabolism. They are unobtrusively included in daily diet in common products as coffee, tea, energetic drinks, or chocolate. Caffeine is by far the most studied methylxanthine either in animal or epidemiologic studies. Theophylline and theobromine are other relevant methylxanthines also commonly available in the aforementioned sources. There are many disseminated myths about methylxanthines but there is increased scientific knowledge to discuss all the controversy and promise shown by these intriguing phytochemicals. In fact, many beneficial physiologic outcomes have been suggested for methylxanthines in areas as important and diverse as neurodegenerative and respiratory diseases, diabetes or cancer. However, there have always been toxicity concerns with methylxanthine (over)consumption and pharmacologic applications. Herein, we explore the structure-bioactivity relationships to bring light those enumerated effects. The potential shown by methylxanthines in such a wide range of conditions should substantiate many other scientific endeavors that may highlight their adequacy as adjuvant therapy agents and may contribute to the advent of functional foods. Newly designed targeted molecules based on methylxanthine structure may originate more specific and effective outcomes. Full article
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7321 KiB  
Article
Intra-Population Variation of Secondary Metabolites in Cistus ladanifer L.
by Cristina Valares Masa, Juan Carlos Alías Gallego, Natividad Chaves Lobón and Teresa Sosa Díaz
Molecules 2016, 21(7), 945; https://doi.org/10.3390/molecules21070945 - 21 Jul 2016
Cited by 12 | Viewed by 5920
Abstract
In previous studies, secondary metabolites in the leaf exudate of Cistus ladanifer, specifically aglycone flavonoids and diterpenes, were demonstrated to play an ecophysiological role. They protect against ultraviolet radiation, have antiherbivore activity, and are allelopathic agents. Their synthesis in the plant was [...] Read more.
In previous studies, secondary metabolites in the leaf exudate of Cistus ladanifer, specifically aglycone flavonoids and diterpenes, were demonstrated to play an ecophysiological role. They protect against ultraviolet radiation, have antiherbivore activity, and are allelopathic agents. Their synthesis in the plant was also found to vary quantitatively and qualitatively in response to various environmental factors. In view of these findings, the present work was designed to clarify whether within a single population there are differences among individuals subject to the same environmental conditions. To this end, we analyzed the leaves of 100 individuals of C. ladanifer. The results showed the existence of intrapopulational variation, since, although all the individuals had the same composition of secondary chemistry, the amounts were different. The individuals of a given population of C. ladanifer differ from each other even when growing under similar conditions. According to the ammount of flavonoids and diterpenes observed in each individual, it was possible to distinguish four different groups of individuals. Most individuals, evenly distributed within the population, had low concentrations of the studied compounds, whilst other individuals synthesized greater amounts and were randomly distributed among the former. Given the functions of flavonoids and diterpenes in this species, the quantified intra-population variation may involve greater plasticity for the species in the face of environmental changes. Full article
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Article
Metabolomics Provides Quality Characterization of Commercial Gochujang (Fermented Pepper Paste)
by Gyu Min Lee, Dong Ho Suh, Eun Sung Jung and Choong Hwan Lee
Molecules 2016, 21(7), 921; https://doi.org/10.3390/molecules21070921 - 15 Jul 2016
Cited by 18 | Viewed by 7356
Abstract
To identify the major factors contributing to the quality of commercial gochujang (fermented red pepper paste), metabolites were profiled by mass spectrometry. In principal component analysis, cereal type (wheat, brown rice, and white rice) and species of hot pepper (Capsicum annuum, [...] Read more.
To identify the major factors contributing to the quality of commercial gochujang (fermented red pepper paste), metabolites were profiled by mass spectrometry. In principal component analysis, cereal type (wheat, brown rice, and white rice) and species of hot pepper (Capsicum annuum, C. annuum cv. Chung-yang, and C. frutescens) affected clustering patterns. Relative amino acid and citric acid levels were significantly higher in wheat gochujang than in rice gochujang. Sucrose, linoleic acid, oleic acid, and lysophospholipid levels were high in brown-rice gochujang, whereas glucose, maltose, and γ-aminobutyric acid levels were high in white-rice gochujang. The relative capsaicinoid and luteolin derivative contents in gochujang were affected by the hot pepper species used. Gochujang containing C. annuum cv. Chung-yang and C. frutescens showed high capsaicinoid levels. The luteolin derivative level was high in gochujang containing C. frutescens. These metabolite variations in commercial gochujang may be related to different physicochemical phenotypes and antioxidant activity. Full article
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Review
New Perspectives on the Use of Phytochemicals as an Emergent Strategy to Control Bacterial Infections Including Biofilms
by Anabela Borges, Ana Cristina Abreu, Carla Dias, Maria José Saavedra, Fernanda Borges and Manuel Simões
Molecules 2016, 21(7), 877; https://doi.org/10.3390/molecules21070877 - 05 Jul 2016
Cited by 162 | Viewed by 15627
Abstract
The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs [...] Read more.
The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs not as vulnerable as the current ones to bacterial resistance mechanisms, and also able to target bacteria in biofilms. Natural products, especially those obtained from plants, have proven to be outstanding compounds with unique properties, making them perfect candidates for these much-needed therapeutics. This review presents the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. Further, the difficulties associated with the use of the existing antibiotics in the treatment of biofilm-related infections are described. To counteract the biofilm resistance problems, innovative strategies are suggested based on literature data. Among the proposed strategies, the use of phytochemicals to inhibit or eradicate biofilms is highlighted. An overview on the use of phytochemicals to interfere with bacterial quorum sensing (QS) signaling pathways and underlying phenotypes is provided. The use of phytochemicals as chelating agents and efflux pump inhibitors is also reviewed. Full article
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Article
Chemical Profile, Antioxidant and Antibacterial Activities of Achillea moschata Wulfen, an Endemic Species from the Alps
by Sara Vitalini, Moira Madeo, Aldo Tava, Marcello Iriti, Lisa Vallone, Pinarosa Avato, Clementina Elvezia Cocuzza, Paolo Simonetti and Maria Pia Argentieri
Molecules 2016, 21(7), 830; https://doi.org/10.3390/molecules21070830 - 25 Jun 2016
Cited by 32 | Viewed by 6229
Abstract
Aerial parts of Achillea moschata Wulfen (Asteraceae) growing wild in the Italian Rhaetian Alps were investigated to describe, for the first time, their phenolic content, as well as to characterize the essential oil. Inspection of the metabolic profile combining HPLC-DAD and ESI-MS/MS data [...] Read more.
Aerial parts of Achillea moschata Wulfen (Asteraceae) growing wild in the Italian Rhaetian Alps were investigated to describe, for the first time, their phenolic content, as well as to characterize the essential oil. Inspection of the metabolic profile combining HPLC-DAD and ESI-MS/MS data showed that the methanol extract contained glycosylated flavonoids with luteolin and apigenin as the main aglycones. Among them, the major compound was 7-O-glucosyl apigenin. Caffeoyl derivates were other phenolics identified. The essential oil obtained by steam distillation and investigated by GC/FID and GC/MS showed camphor, 1,8-cineole, and bornylacetate as the main constituents. The antioxidant capacity of three different extracts with increasing polarity and of the essential oil was evaluated by employing ABTS·+ and DPPH· radical scavenging assays. The methanolic extract was the only significantly effective sample against both synthetic radicals. All samples were also tested against Gram-positive (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa) bacterial species using the disk diffusion assay. The non-polar extracts (dichloromethane and petroleum ether) and the essential oil possessed a broad spectrum of antimicrobial activity expressed according to inhibition zone diameter (8–24 mm). Full article
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Article
Ultrahigh Pressure Processing Produces Alterations in the Metabolite Profiles of Panax ginseng
by Mee Youn Lee, Digar Singh, Sung Han Kim, Sang Jun Lee and Choong Hwan Lee
Molecules 2016, 21(6), 816; https://doi.org/10.3390/molecules21060816 - 22 Jun 2016
Cited by 11 | Viewed by 5556
Abstract
Ultrahigh pressure (UHP) treatments are non-thermal processing methods that have customarily been employed to enhance the quality and productivity of plant consumables. We aimed to evaluate the effects of UHP treatments on ginseng samples (white ginseng: WG; UHP-treated WG: UWG; red ginseng: RG; [...] Read more.
Ultrahigh pressure (UHP) treatments are non-thermal processing methods that have customarily been employed to enhance the quality and productivity of plant consumables. We aimed to evaluate the effects of UHP treatments on ginseng samples (white ginseng: WG; UHP-treated WG: UWG; red ginseng: RG; UHP-treated RG: URG; ginseng berries: GB; and UHP-treated GB: UGB) using metabolite profiling based on ultrahigh performance liquid chromatography-linear trap quadrupole-ion trap-tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Multivariate data analyses revealed a clear demarcation among the GB and UGB samples, and the phenotypic evaluations correlated the highest antioxidant activities and the total phenolic and flavonoid compositions with the UGB samples. Overall, eight amino acids, seven organic acids, seven sugars and sugar derivatives, two fatty acids, three notoginsenosides, three malonylginsenosides, and three ginsenosides, were identified as significantly discriminant metabolites between the GB and UGB samples, with relatively higher proportions in the latter. Ideally, these metabolites can be used as quality biomarkers for the assessment of ginseng products and our results indicate that UHP treatment likely led to an elevation in the proportions of total extractable metabolites in ginseng samples. Full article
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Article
Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G
by Eduarda C. Costa, Tatiana B. Cassamale, Diego B. Carvalho, Lauriane S. S. Bosquiroli, Mariáh Ojeda, Thalita V. Ximenes, Maria F. C. Matos, Mônica C. T. Kadri, Adriano C. M. Baroni and Carla C. P. Arruda
Molecules 2016, 21(6), 802; https://doi.org/10.3390/molecules21060802 - 20 Jun 2016
Cited by 31 | Viewed by 6426
Abstract
Sixteen 1,4-diaryl-1,2,3-triazole compounds 419 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 419 were synthetized via Click Chemistry strategy by [...] Read more.
Sixteen 1,4-diaryl-1,2,3-triazole compounds 419 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 419 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities. Full article
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Article
In Vitro Assessment of CYP-Mediated Drug Interactions for Kinsenoside, an Antihyperlipidemic Candidate
by Shaheed Ur Rehman, Min Sun Choi, In Sook Kim, Zengwei Luo, Yongbo Xue, Guangming Yao, Yonghui Zhang and Hye Hyun Yoo
Molecules 2016, 21(6), 800; https://doi.org/10.3390/molecules21060800 - 18 Jun 2016
Cited by 4 | Viewed by 5860
Abstract
Kinsenoside, the herb-derived medicine isolated from the plant Anoect chilus, has diverse pharmacological actions, and it is considered to be a promising antihyperlipidemic drug candidate. This study evaluates the effects of kinsenoside on CYP enzyme-mediated drug metabolism in order to predict the [...] Read more.
Kinsenoside, the herb-derived medicine isolated from the plant Anoect chilus, has diverse pharmacological actions, and it is considered to be a promising antihyperlipidemic drug candidate. This study evaluates the effects of kinsenoside on CYP enzyme-mediated drug metabolism in order to predict the potential for kinsenoside-drug interactions. Kinsenoside was tested at different concentrations of 0.1, 0.3, 1, 3, 10, 30, and 100 µM in human liver microsomes. The c Cktail probe assay based on liquid chromatography-tandem mass spectrometry was conducted to measure the CYP inhibitory effect of kinsenoside. Subsequently, the metabolism profiles of amlodipine and lovastatin in human liver microsomes were analyzed following co-incubation with kinsenoside. The concentration levels of the parent drug and the major metabolites were compared with the kinsenoside-cotreated samples. The effect of kinsenoside was negligible on the enzyme activity of all the CYP isozymes tested even though CYP2A6 was slightly inhibited at higher concentrations. The drug-drug interaction assay also showed that the concomitant use of kinsenoside has a non-significant effect on the concentration of lovastatin or amlodipine, and their major metabolites. So, it was concluded that there is almost no risk of drug interaction between kinsenoside and CYP drug substrates via CYP inhibition. Full article
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Article
Metabolomic Profiles of Aspergillus oryzae and Bacillus amyloliquefaciens During Rice Koji Fermentation
by Da Eun Lee, Sunmin Lee, Eun Seok Jang, Hye Won Shin, Byoung Seok Moon and Choong Hwan Lee
Molecules 2016, 21(6), 773; https://doi.org/10.3390/molecules21060773 - 14 Jun 2016
Cited by 83 | Viewed by 13003
Abstract
Rice koji, used early in the manufacturing process for many fermented foods, produces diverse metabolites and enzymes during fermentation. Using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultrahigh-performance liquid chromatography linear trap quadrupole ion trap tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS), and multivariate analysis we [...] Read more.
Rice koji, used early in the manufacturing process for many fermented foods, produces diverse metabolites and enzymes during fermentation. Using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultrahigh-performance liquid chromatography linear trap quadrupole ion trap tandem mass spectrometry (UHPLC-LTQ-IT-MS/MS), and multivariate analysis we generated the metabolite profiles of rice koji produced by fermentation with Aspergillus oryzae (RK_AO) or Bacillus amyloliquefaciens (RK_BA) for different durations. Two principal components of the metabolomic data distinguished the rice koji samples according to their fermenter species and fermentation time. Several enzymes secreted by the fermenter species, including α-amylase, protease, and β-glucosidase, were assayed to identify differences in expression levels. This approach revealed that carbohydrate metabolism, serine-derived amino acids, and fatty acids were associated with rice koji fermentation by A. oryzae, whereas aromatic and branched chain amino acids, flavonoids, and lysophospholipids were more typical in rice koji fermentation by B. amyloliquefaciens. Antioxidant activity was significantly higher for RK_BA than for RK_AO, as were the abundances of flavonoids, including tricin, tricin glycosides, apigenin glycosides, and chrysoeriol glycosides. In summary, we have used MS-based metabolomics and enzyme activity assays to evaluate the effects of using different microbial species and fermentation times on the nutritional profile of rice koji. Full article
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Article
Probing Steroidal Substrate Specificity of Cytochrome P450 BM3 Variants
by Xing Liu, Zhi-Biao Wang, Ya-Nan Wang and Jian-Qiang Kong
Molecules 2016, 21(6), 760; https://doi.org/10.3390/molecules21060760 - 11 Jun 2016
Cited by 11 | Viewed by 5744
Abstract
M01A82W, M11A82W and M01A82WS72I are three cytochrome P450 BM3 (CYP102A1) variants. They can catalyze the hydroxylation of testosterone (TES) and norethisterone at different positions, thereby making them promising biocatalysts for steroid hydroxylation. With the aim of obtaining more hydroxylated steroid precursors it is [...] Read more.
M01A82W, M11A82W and M01A82WS72I are three cytochrome P450 BM3 (CYP102A1) variants. They can catalyze the hydroxylation of testosterone (TES) and norethisterone at different positions, thereby making them promising biocatalysts for steroid hydroxylation. With the aim of obtaining more hydroxylated steroid precursors it is necessary to probe the steroidal substrate diversity of these BM3 variants. Here, three purified BM3 variants were first incubated with eight steroids, including testosterone (TES), methyltestosterone (MT), cholesterol, β-sitosterol, dehydroepiandrosterone (DHEA), diosgenin, pregnenolone and ergosterol. The results indicated that the two 3-keto-Δ4-steroids TES and MT can be hydroxylated at various positions by the three BM3 mutants, respectively. On the contrary, the three enzymes displayed no any activity toward the remaining six 3-hydroxy-Δ5-steroids. This result indicates that the BM3 mutants prefer 3-keto-Δ4-steroids as hydroxylation substrates. To further verify this notion, five other substrates, including two 3-hydroxy-Δ5-steroids and three 3-keto-Δ4-steroids, were carefully selected to incubate with the three BM3 variants. The results indicated the three 3-keto-Δ4-steroids can be metabolized to form hydroxysteroids by the three BM3 variants. On the other hand, the two 3-hydroxy-Δ5-steroids cannot be hydroxylated at any position by the BM3 mutants. These results further support the above conclusion, therefore demonstrating the 3-keto-Δ4–steroid substrate preference of BM3 mutants, and laying a foundation for microbial production of more hydroxylated steroid intermediates using BM3 variants. Full article
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Article
Polyphenols from Erythrina crista-galli: Structures, Molecular Docking and Phytoestrogenic Activity
by Naglaa S. Ashmawy, Mohamed L. Ashour, Michael Wink, Mohamed El-Shazly, Fang-Rong Chang, Noha Swilam, Ashraf B. Abdel-Naim and Nahla Ayoub
Molecules 2016, 21(6), 726; https://doi.org/10.3390/molecules21060726 - 03 Jun 2016
Cited by 14 | Viewed by 7177
Abstract
Objectives: The current study aimed at exploring the secondary metabolites content of Erythrina crista-galli aqueous methanol extract and assessing its phytoestrogenic and cytoprotective activities. Methods: Isolation of the compounds was carried out using conventional chromatographic techniques. The structures of the isolated compounds were [...] Read more.
Objectives: The current study aimed at exploring the secondary metabolites content of Erythrina crista-galli aqueous methanol extract and assessing its phytoestrogenic and cytoprotective activities. Methods: Isolation of the compounds was carried out using conventional chromatographic techniques. The structures of the isolated compounds were elucidated based on the UV, NMR spectral data along with their mass-spectrometric analyses. The phytoestrogenic activity was evaluated in-silico and in vitro using the Arabidopsis thaliana pER8: GUS reporter assay and the proliferation-enhancing activity of MCF-7 cells. Key findings: Phytochemical investigation of E. crista-galli aqueous methanol extract resulted in the isolation and identification of five flavonoids. The plant extract and its fractions showed significant estrogenic activities compared to controls. Conclusion: Five flavonoids were identified from E. crista-galli aqueous methanol extract. To the best of our knowledge, among these flavonoids, apigenin-7-O-rhamnosyl-6-C-glucoside was isolated for the first time from nature. Moreover, luteolin-6-C-glucoside was isolated for the first time from this plant. The plant revealed promising phytoestrogenic activities. This gives rationale to some of its pharmacological properties and suggests additional phytoestrogenic effects, which have not been reported yet. Full article
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Article
Analysis of Potential Amino Acid Biomarkers in Brain Tissue and the Effect of Galangin on Cerebral Ischemia
by Ruocong Yang, Kun Chen, Yanyan Zhao, Pengpeng Tian, Feipeng Duan, Wenli Sun, Yuxin Liu, Zhiyong Yan and Shaojing Li
Molecules 2016, 21(4), 438; https://doi.org/10.3390/molecules21040438 - 06 Apr 2016
Cited by 14 | Viewed by 5462
Abstract
Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin [...] Read more.
Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin provides direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids in ischemic stroke; however, the mechanism of the changes of amino acids in the ischemic brain tissue has not yet been clarified. In this paper, we explored brain tissue amino acid biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. Finally, we identified that glutamic acid, alanine and aspartic acid showed significant changes (p < 0.05 or p < 0.01) in galangin-treated groups compared with vehicle-treated rats and the four enzymes associated with these three AAs’ metabolic pathways; GLUD1, SLC16A10, SLC1A1 and GPT were identified by multiplex interactions with the three amino acids. By metabolite-protein network analysis and molecular docking, six of 28 proteins were identified and might become potential galangin biomarkers for acute ischemic stroke. The data in our study provides thoughts for exploring the mechanism of disease, discovering new targets for drug candidates and elucidating the related regulatory signal network. Full article
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Article
Pharmacokinetics of Maleic Acid as a Food Adulterant Determined by Microdialysis in Rat Blood and Kidney Cortex
by Mei-Ling Hou, Chia-Ming Lu, Chi-Hung Lin, Lie-Chwen Lin and Tung-Hu Tsai
Molecules 2016, 21(3), 367; https://doi.org/10.3390/molecules21030367 - 17 Mar 2016
Cited by 6 | Viewed by 5397
Abstract
Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical [...] Read more.
Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively). The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC) of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively), indicating that greater accumulation of maleic acid occurred in the rat kidney. Full article
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Article
Quantitative Variation of Flavonoids and Diterpenes in Leaves and Stems of Cistus ladanifer L. at Different Ages
by Cristina Valares Masa, Teresa Sosa Díaz, Juan Carlos Alías Gallego and Natividad Chaves Lobón
Molecules 2016, 21(3), 275; https://doi.org/10.3390/molecules21030275 - 27 Feb 2016
Cited by 26 | Viewed by 6066
Abstract
The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of [...] Read more.
The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of the plant and they may be modified as a response to biotic and/or abiotic stress. As a consequence, the resistance state of a plant may vary in space and time. The secondary metabolites of Cistus ladanifer have been quantified in leaves and stems throughout autumn, winter, spring and summer, and at different ages of the plant. This study shows that there are significant differences between young leaves, mature leaves and stems, and between individuals of different ages. Young leaves show significantly greater synthesis of flavonoids and diterpenes than mature leaves and stems, with a clear seasonal variation, and the differences between leaves at different growth stages and stems is maintained during the quantified seasons. With respect to age, specimens under one year of age secreted significantly lower amounts of compounds. The variation in the composition of secondary metabolites between different parts of the plant, the season and the variations in age may determine the interactions of Cistus ladanifer with the biotic and abiotic factors to which it is exposed. Full article
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Review
The Impact of Melatonin in Research
by Elena Maria Varoni, Clelia Soru, Roberta Pluchino, Chiara Intra and Marcello Iriti
Molecules 2016, 21(2), 240; https://doi.org/10.3390/molecules21020240 - 20 Feb 2016
Cited by 16 | Viewed by 7083
Abstract
Citation indexes represent helpful tools for evaluating the impact of articles on research. The aim of this study was to obtain the top-100 ranking of the most cited papers on melatonin, a relevant neurohormone mainly involved in phase-adjusting the biological clock and with [...] Read more.
Citation indexes represent helpful tools for evaluating the impact of articles on research. The aim of this study was to obtain the top-100 ranking of the most cited papers on melatonin, a relevant neurohormone mainly involved in phase-adjusting the biological clock and with certain sleep-promoting capability. An article search was carried out on the Institute for Scientific Information (ISI) Web of Science platform. Numbers of citations, names of authors, journals and their 2014-impact factor, year of publication, and experimental designs of studies were recorded. The ranking of the 100-most cited articles on melatonin research (up to February 2016) revealed a citation range from 1623 to 310. Narrative reviews/expert opinions were the most frequently cited articles, while the main research topics were oxidative stress, sleep physiology, reproduction, circadian rhythms and melatonin receptors. This study represents the first detailed analysis of the 100 top-cited articles published in the field of melatonin research, showing its impact and relevance in the biomedical field. Full article
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Article
Chemical Characterization and Trypanocidal, Leishmanicidal and Cytotoxicity Potential of Lantana camara L. (Verbenaceae) Essential Oil
by Luiz Marivando Barros, Antonia Eliene Duarte, Maria Flaviana Bezerra Morais-Braga, Emily Pansera Waczuk, Celeste Vega, Nadghia Figueiredo Leite, Irwin Rose Alencar De Menezes, Henrique Douglas Melo Coutinho, João Batista Teixeira Rocha and Jean Paul Kamdem
Molecules 2016, 21(2), 209; https://doi.org/10.3390/molecules21020209 - 10 Feb 2016
Cited by 36 | Viewed by 8364
Abstract
Drug resistance in the treatment of neglected parasitic diseases, such as leishmaniasis and trypanosomiasis, has led to the search and development of alternative drugs from plant origins. In this context, the essential oil extracted by hydro-distillation from Lantana camara leaves was tested against [...] Read more.
Drug resistance in the treatment of neglected parasitic diseases, such as leishmaniasis and trypanosomiasis, has led to the search and development of alternative drugs from plant origins. In this context, the essential oil extracted by hydro-distillation from Lantana camara leaves was tested against Leishmania braziliensis and Trypanosoma cruzi. The results demonstrated that L. camara essential oil inhibited T. cruzi and L. braziliensis with IC50 of 201.94 μg/mL and 72.31 μg/mL, respectively. L. camara essential oil was found to be toxic to NCTC929 fibroblasts at 500 μg/mL (IC50 = 301.42 μg/mL). The composition of L. camara essential oil analyzed by gas chromatography–mass spectrometry (GC/MS) revealed large amounts of (E)-caryophyllene (23.75%), biciclogermacrene (15.80%), germacrene D (11.73%), terpinolene (6.1%), and sabinene (5.92%), which might be, at least in part, responsible for its activity. Taken together, our results suggest that L. camara essential oil may be an important source of therapeutic agents for the development of alternative drugs against parasitic diseases. Full article
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Article
Comparative Evaluation of Total Antioxidant Capacities of Plant Polyphenols
by Kristóf Csepregi, Susanne Neugart, Monika Schreiner and Éva Hideg
Molecules 2016, 21(2), 208; https://doi.org/10.3390/molecules21020208 - 09 Feb 2016
Cited by 152 | Viewed by 13516
Abstract
Thirty-seven samples of naturally occurring phenolic compounds were evaluated using three common in vitro assays for total antioxidant activity (TAC) testing: the Trolox Equivalent Antioxidant Capacity (TEAC), the Ferric Reducing Antioxidant Potential (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, in addition to [...] Read more.
Thirty-seven samples of naturally occurring phenolic compounds were evaluated using three common in vitro assays for total antioxidant activity (TAC) testing: the Trolox Equivalent Antioxidant Capacity (TEAC), the Ferric Reducing Antioxidant Potential (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, in addition to the Folin-Ciocalteu reagent reactivity (FCR). We found that antioxidant hierarchies depended on the choice of assay and applied ANOVA analyses to explore underlying structure-TAC dependencies. In addition to statistically confirming the empirically established connection between flavonoid ring-B catechol and high TEAC or FRAP, new correlations were also found. In flavonoids, (i) hydroxyl groups on ring-B had a positive effect on all four TAC assays; (ii) the presence of a 3-hydroxyl group on ring-C increased TEAC and FRAP, but had no effect on DPPH or FCR; (iii) Phenolic acids lacking a 3-hydroxyl group had significantly lower FRAP or DPPH than compounds having this structure, while TEAC or FCR were not affected. Results demonstrated that any TAC-based ranking of phenolic rich samples would very much depend on the choice of assay, and argue for use of more than one technique. As an illustration, we compared results of the above four assays using either grapevine leaf extracts or synthetic mixtures of compounds prepared according to major polyphenols identified in the leaves. Full article
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Correction
Correction: Rzepecka-Stojko, A., et al. Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity. Molecules 2015, 20, 21732–21749
by Anna Rzepecka-Stojko, Jerzy Stojko, Anna Kurek-Górecka, Michał Górecki, Agata Kabała-Dzik, Robert Kubina, Aleksandra Moździerz and Ewa Buszman
Molecules 2016, 21(2), 159; https://doi.org/10.3390/molecules21020159 - 28 Jan 2016
Cited by 1 | Viewed by 4048
Abstract
The authors wish to make the following corrections to this paper: [...] Full article

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1510 KiB  
Article
Effect of Three Training Systems on Grapes in a Wet Region of China: Yield, Incidence of Disease and Anthocyanin Compositions of Vitis vinifera cv. Cabernet Sauvignon
by Mei-Ying Liu, Ming Chi, Yong-Hong Tang, Chang-Zheng Song, Zhu-Mei Xi and Zhen-Wen Zhang
Molecules 2015, 20(10), 18967-18987; https://doi.org/10.3390/molecules201018967 - 19 Oct 2015
Cited by 12 | Viewed by 6648
Abstract
Grapevine training systems determine the suitability for grape varieties in a specific growing region. We evaluated the influence of three training systems, Single Guyot (SG), Spur-pruned Vertical Shoot-Positioned (VSP), and Four-Arm Kniffin (4AK), on the performance of grapes and vines of Vitis vinifera [...] Read more.
Grapevine training systems determine the suitability for grape varieties in a specific growing region. We evaluated the influence of three training systems, Single Guyot (SG), Spur-pruned Vertical Shoot-Positioned (VSP), and Four-Arm Kniffin (4AK), on the performance of grapes and vines of Vitis vinifera L. cv. Cabernet Sauvignon in the 2012 and 2013 growing seasons in a wet region of central China. 4AK was the most productive system in comparison to SG and VSP. SG and VSP had lower disease infections of leaves and berries, especially in the mid- and final stage of berry ripening. Three training systems had no impact on berry maturity. PLS-DA (Partial Least Squares-Discriminant) analysis showed that the relatively dry vintage could well discriminate three training systems, but the wet vintage was not. A wet vintage of 2013 had more accumulation of 3′5′-substituted and acylated anthocyanins, including malvidin-3-O-(6-O-acetyl)-glucoside, malvidin-3-O-glucoside, and petunidin-3-O-(cis-6-O-coumaryl)-glucoside, etc. With regard to the effect of training systems, 4AK grapes had the lowest concentrations of total anthocyanins and individual anthocyanins, SG and VSP differed according to the different vintages, and showed highest concentration of total individual anthocyanins in 2012 and 2013, respectively. Generally, VSP benefited the most, contributing to significantly highest levels of total individual anthocyanins, and major anthocyanin, including malvidin-3-O-glucoside and malvidin-3-O-(6-O-acetyl)-glucoside, and the grapes obtained from VSP presented significantly highest proportion of 3′5′-substituted anthocyanins. With regard to the ratios of 3′5′/3′-substituted, methoxylated/non-methoxylated and acylated/non-acylated anthocyanins, the significantly higher levels were also shown in VSP system. In summary, VSP was the best training system for Cabernet Sauvignon to accumulate relatively stable individual anthocyanins in this wet region of China and potentially in other rainy regions. Full article
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1262 KiB  
Article
Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception
by Giuseppe Mancuso, Gigliola Borgonovo, Leonardo Scaglioni and Angela Bassoli
Molecules 2015, 20(10), 18907-18922; https://doi.org/10.3390/molecules201018907 - 16 Oct 2015
Cited by 32 | Viewed by 9166
Abstract
Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two [...] Read more.
Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels. Full article
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Article
Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats
by Takashi Matsumoto, Yousuke Matsubara, Yasuharu Mizuhara, Kyoji Sekiguchi, Junichi Koseki, Kazuaki Tsuchiya, Hiroaki Nishimura, Junko Watanabe, Atsushi Kaneko, Kazuya Maemura, Tomohisa Hattori and Yoshio Kase
Molecules 2015, 20(10), 18031-18046; https://doi.org/10.3390/molecules201018031 - 30 Sep 2015
Cited by 20 | Viewed by 7593
Abstract
Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases [...] Read more.
Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs. Full article
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Review
Wheat Bran Phenolic Acids: Bioavailability and Stability in Whole Wheat-Based Foods
by Barbara Laddomada, Sofia Caretto and Giovanni Mita
Molecules 2015, 20(9), 15666-15685; https://doi.org/10.3390/molecules200915666 - 28 Aug 2015
Cited by 112 | Viewed by 10923
Abstract
Wheat bran is generally considered a byproduct of the flour milling industry, but it is a great source of fibers, minerals, and antioxidants that are important for human health. Phenolic acids are a specific class of wheat bran components that may act as [...] Read more.
Wheat bran is generally considered a byproduct of the flour milling industry, but it is a great source of fibers, minerals, and antioxidants that are important for human health. Phenolic acids are a specific class of wheat bran components that may act as antioxidants to prevent heart disease and to lower the incidence of colon cancer. Moreover, phenolic acids have anti-inflammatory properties that are potentially significant for the promotion of gastrointestinal health. Evidence on the beneficial effects of phenolic acids as well as of other wheat bran components is encouraging the use of wheat bran as an ingredient of functional foods. After an overview of the chemistry, function, and bioavailability of wheat phenolic acids, the discussion will focus on how technologies can allow the formulation of new, functional whole wheat products with enhanced health-promoting value and safety without renouncing the good-tasting standards that are required by consumers. Finally, this review summarizes the latest studies about the stability of phenolic acids in wheat foods fortified by the addition of wheat bran, pearled fractions, or wheat bran extracts. Full article
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Article
Inhibition of Oral Streptococci Growth Induced by the Complementary Action of Berberine Chloride and Antibacterial Compounds
by Arkadiusz Dziedzic, Robert D. Wojtyczka and Robert Kubina
Molecules 2015, 20(8), 13705-13724; https://doi.org/10.3390/molecules200813705 - 28 Jul 2015
Cited by 35 | Viewed by 7856
Abstract
Synergistic interactions between natural bioactive compounds from medicinal plants and antibiotics may exhibit therapeutic benefits, acting against oral cariogenic and opportunistic pathogens. The aim of the presented work was to assess the antibacterial activity of berberine chloride (BECl) in light of the effect [...] Read more.
Synergistic interactions between natural bioactive compounds from medicinal plants and antibiotics may exhibit therapeutic benefits, acting against oral cariogenic and opportunistic pathogens. The aim of the presented work was to assess the antibacterial activity of berberine chloride (BECl) in light of the effect exerted by common antibiotics on selected reference strains of oral streptococci (OST), and to evaluate the magnitude of interactions. Three representative oral microorganisms were investigated: Streptococcus mutans ATCC 25175 (SM), S. sanguinis ATCC 10556 (SS), S. oralis ATCC 9811 (SO) and microdilution tests, along with disc diffusion assays were applied. Here, we report that growth (viability) of all oral streptococci was reduced by exposure to BECl and was dependent primarily on exposure/ incubation time. A minimum inhibitory concentrations (MIC) of BECl against OST ranged from 512 µg/mL (SS) to 1024 µg/mL (SM, SO). The most noticeable antibacterial effects were observed for S. sanguinis (MIC 512 µg/mL) and the most significant synergistic action was found for the combinations BECl-penicillin, BECl-clindamycin and BECl-erythromycin. The S. oralis reflects the highest MBC value as assessed by the AlamarBlue assay (2058 µg/mL). The synergy between berberine and common antibiotics demonstrates its potential use as a novel antibacterial tool for opportunistic infections and also provides a rational basis for the use of berberine as an oral hygiene measure. Full article
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Article
Metabolic Analysis of Various Date Palm Fruit (Phoenix dactylifera L.) Cultivars from Saudi Arabia to Assess Their Nutritional Quality
by Ismail Hamad, Hamada AbdElgawad, Soad Al Jaouni, Gaurav Zinta, Han Asard, Sherif Hassan, Momtaz Hegab, Nashwa Hagagy and Samy Selim
Molecules 2015, 20(8), 13620-13641; https://doi.org/10.3390/molecules200813620 - 27 Jul 2015
Cited by 178 | Viewed by 11024
Abstract
Date palm is an important crop, especially in the hot-arid regions of the world. Date palm fruits have high nutritional and therapeutic value and possess significant antibacterial and antifungal properties. In this study, we performed bioactivity analyses and metabolic profiling of date fruits [...] Read more.
Date palm is an important crop, especially in the hot-arid regions of the world. Date palm fruits have high nutritional and therapeutic value and possess significant antibacterial and antifungal properties. In this study, we performed bioactivity analyses and metabolic profiling of date fruits of 12 cultivars from Saudi Arabia to assess their nutritional value. Our results showed that the date extracts from different cultivars have different free radical scavenging and anti-lipid peroxidation activities. Moreover, the cultivars showed significant differences in their chemical composition, e.g., the phenolic content (10.4–22.1 mg/100 g DW), amino acids (37–108 μmol·g−1 FW) and minerals (237–969 mg/100 g DW). Principal component analysis (PCA) showed a clear separation of the cultivars into four different groups. The first group consisted of the Sokary, Nabtit Ali cultivars, the second group of Khlas Al Kharj, Khla Al Qassim, Mabroom, Khlas Al Ahsa, the third group of Khals Elshiokh, Nabot Saif, Khodry, and the fourth group consisted of Ajwa Al Madinah, Saffawy, Rashodia, cultivars. Hierarchical cluster analysis (HCA) revealed clustering of date cultivars into two groups. The first cluster consisted of the Sokary, Rashodia and Nabtit Ali cultivars, and the second cluster contained all the other tested cultivars. These results indicate that date fruits have high nutritive value, and different cultivars have different chemical composition. Full article
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Review
Secondary Metabolites from Rubiaceae Species
by Daiane Martins and Cecilia Veronica Nunez
Molecules 2015, 20(7), 13422-13495; https://doi.org/10.3390/molecules200713422 - 22 Jul 2015
Cited by 101 | Viewed by 17792
Abstract
This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, [...] Read more.
This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones, triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have shown to be the most common. These compounds have been mostly isolated from the genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza and Morinda. The occurrence and distribution of iridoids, alkaloids and anthraquinones point out their chemotaxonomic correlation among tribes and subfamilies. From an evolutionary point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so specific in Rubioideae, can explain this and large amounts of both iridoids and indole alkaloids are produced. In Ixoroideae, the most active biosysthetic pathway is the one that produces iridoids; while in Cinchonoideae, it produces indole alkaloids together with other alkaloids. The chemical biosynthetic pathway now supports this botanical conclusion. Full article
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Article
Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells
by Chloe D. Goldsmith, Quan V. Vuong, Elham Sadeqzadeh, Costas E. Stathopoulos, Paul D. Roach and Christopher J. Scarlett
Molecules 2015, 20(7), 12992-13004; https://doi.org/10.3390/molecules200712992 - 17 Jul 2015
Cited by 51 | Viewed by 8951
Abstract
Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the [...] Read more.
Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits. Full article
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1559 KiB  
Review
Tilting Plant Metabolism for Improved Metabolite Biosynthesis and Enhanced Human Benefit
by Bhekumthetho Ncube and Johannes Van Staden
Molecules 2015, 20(7), 12698-12731; https://doi.org/10.3390/molecules200712698 - 13 Jul 2015
Cited by 94 | Viewed by 13637
Abstract
The immense chemical diversity of plant-derived secondary metabolites coupled with their vast array of biological functions has seen this group of compounds attract considerable research interest across a range of research disciplines. Medicinal and aromatic plants, in particular, have been exploited for this [...] Read more.
The immense chemical diversity of plant-derived secondary metabolites coupled with their vast array of biological functions has seen this group of compounds attract considerable research interest across a range of research disciplines. Medicinal and aromatic plants, in particular, have been exploited for this biogenic pool of phytochemicals for products such as pharmaceuticals, fragrances, dyes, and insecticides, among others. With consumers showing increasing interests in these products, innovative biotechnological techniques are being developed and employed to alter plant secondary metabolism in efforts to improve on the quality and quantity of specific metabolites of interest. This review provides an overview of the biosynthesis for phytochemical compounds with medicinal and other related properties and their associated biological activities. It also provides an insight into how their biosynthesis/biosynthetic pathways have been modified/altered to enhance production. Full article
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Article
Phytochemical Profiling and Evaluation of Pharmacological Activities of Hypericum scabrum L.
by Lan Jiang, Sodik Numonov, Khayrulla Bobakulov, Muhammad Nasimullah Qureshi, Haiqing Zhao and Haji Akber Aisa
Molecules 2015, 20(6), 11257-11271; https://doi.org/10.3390/molecules200611257 - 18 Jun 2015
Cited by 46 | Viewed by 6850
Abstract
Phytochemical investigations of ethyl acetate-soluble part of the aerial part of Hypericum scabrum L. delivered eight pure phenolic compounds 18. The pure compounds were identified through physico-chemical, NMR (1D, 2D) and mass spectrometric studies as: 3-8′′-bisapigenin (1), quercetin [...] Read more.
Phytochemical investigations of ethyl acetate-soluble part of the aerial part of Hypericum scabrum L. delivered eight pure phenolic compounds 18. The pure compounds were identified through physico-chemical, NMR (1D, 2D) and mass spectrometric studies as: 3-8′′-bisapigenin (1), quercetin (2), quercetin-3-O-α-l-arabinofuranoside (3), quercetin-3-O-α-l-rhamnoside (4), quercetin-3-O-β-d-glucopyranoside (5), quercetin-3-O-β-d-galactopyranoside (6), (−)-epicatechin (7), (+)-catechin (8). Total polyphenolic compounds and total flavonoids contents were determined in the extract as 0.107 mg∙mg−1 and 0.023 mg∙mg−1 of the dried extract, respectively. Antioxidant activity using DPPH free radical scavenging assay delivered very strong activity for compounds 2 and 5, 6 and crude extract 10. Protein tyrosine phosphatase 1B (PTP-1B) inhibition experiment of isolated compounds and crude extracts resulted in significant inhibition activity for samples 2, 7a, 8a, 11 and 12 with IC50 values ranging from 1.57 to 2.91 µM. Antimicrobial activity of the pure compounds and extracts produced average results against Staphylococcus aureus, Escherichia coli and Candida albicans strains. From our literature survey, it appears that all pure compounds except 2 were isolated and reported for the first time in H. scabrum. Full article
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2345 KiB  
Article
Essential Oil from Berries of Lebanese Juniperus excelsa M. Bieb Displays Similar Antibacterial Activity to Chlorhexidine but Higher Cytocompatibility with Human Oral Primary Cells
by Barbara Azzimonti, Andrea Cochis, Marc El Beyrouthy, Marcello Iriti, Francesca Uberti, Rita Sorrentino, Manuela Miriam Landini, Lia Rimondini and Elena Maria Varoni
Molecules 2015, 20(5), 9344-9357; https://doi.org/10.3390/molecules20059344 - 21 May 2015
Cited by 48 | Viewed by 7961
Abstract
Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with [...] Read more.
Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with 0.05% CHX. The EO was extracted from berries by hydrodistillation and components identified by gas chromatography and mass spectrometry. Bacterial inhibition halo analysis, quantitative cell viability 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT), and colony forming unit (CFU) count were evaluated against the two biofilm formers Aggregatibacter actinomycetemcomitans and Streptococcus mutans. Finally, cytocompatibility was assessed with human primary gingival fibroblasts (HGF) and mucosal keratinocytes (HK). The resulting EO was mainly composed of monoterpene hydrocarbons and oxygenated monoterpenes. An inhibition halo test demonstrated that both bacteria were sensitive to the EO; XTT analysis and CFU counts confirmed that 10-fold-diluted EO determined a statistically significant (p < 0.05) reduction in bacteria count and viability towards both biofilm and planktonic forms in a comparable manner to those obtained with CHX. Moreover, EO displayed higher cytocompatibility than CHX (p < 0.05). In conclusion, EO exhibited bactericidal activity similar to CHX, but a superior cytocompatibility, making it a promising antiseptic alternative to CHX. Full article
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1989 KiB  
Article
Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines
by Anna Rzepecka-Stojko, Agata Kabała-Dzik, Aleksandra Moździerz, Robert Kubina, Robert D. Wojtyczka, Rafał Stojko, Arkadiusz Dziedzic, Żaneta Jastrzębska-Stojko, Magdalena Jurzak, Ewa Buszman and Jerzy Stojko
Molecules 2015, 20(5), 9242-9262; https://doi.org/10.3390/molecules20059242 - 20 May 2015
Cited by 58 | Viewed by 9812
Abstract
Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity [...] Read more.
Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP) and its derivative caffeic acid phenethyl ester (CAPE) towards two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH) assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL−1 for MDA-MB-23 cells and 33.68 µg∙mL−1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs. Full article
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Review
Phytomelatonin: Assisting Plants to Survive and Thrive
by Russel J. Reiter, Dun-Xian Tan, Zhou Zhou, Maria Helena Coelho Cruz, Lorena Fuentes-Broto and Annia Galano
Molecules 2015, 20(4), 7396-7437; https://doi.org/10.3390/molecules20047396 - 22 Apr 2015
Cited by 295 | Viewed by 18594
Abstract
This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots [...] Read more.
This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots versus leaves, and with their developmental stage. As in animals, the pathway of melatonin synthesis in plants utilizes tryptophan as an essential precursor molecule. Melatonin synthesis is inducible in plants when they are exposed to abiotic stresses (extremes of temperature, toxins, increased soil salinity, drought, etc.) as well as to biotic stresses (fungal infection). Melatonin aids plants in terms of root growth, leaf morphology, chlorophyll preservation and fruit development. There is also evidence that exogenously-applied melatonin improves seed germination, plant growth and crop yield and its application to plant products post-harvest shows that melatonin advances fruit ripening and may improve food quality. Since melatonin was only discovered in plants two decades ago, there is still a great deal to learn about the functional significance of melatonin in plants. It is the hope of the authors that the current review will serve as a stimulus for scientists to join the endeavor of clarifying the function of this phylogenetically-ancient molecule in plants and particularly in reference to the mechanisms by which melatonin mediates its multiple actions. Full article
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Article
Phytochemical Compositions and Biological Activities of Essential Oil from Xanthium strumarium L.
by Javad Sharifi-Rad, Seyedeh Mahsan Hoseini-Alfatemi, Majid Sharifi-Rad, Mehdi Sharifi-Rad, Marcello Iriti, Marzieh Sharifi-Rad, Razieh Sharifi-Rad and Sara Raeisi
Molecules 2015, 20(4), 7034-7047; https://doi.org/10.3390/molecules20047034 - 17 Apr 2015
Cited by 66 | Viewed by 10163
Abstract
The chemical composition of the essential oil (EO) from fresh cocklebur (Xanthium strumarium L.) leaves was investigated by GC-MS. The antimicrobial activity of the EO was tested against Gram-positive and Gram-negative bacteria and fungi. Scolicidal activity was assayed against Echinococcus granulosus protoscolices. [...] Read more.
The chemical composition of the essential oil (EO) from fresh cocklebur (Xanthium strumarium L.) leaves was investigated by GC-MS. The antimicrobial activity of the EO was tested against Gram-positive and Gram-negative bacteria and fungi. Scolicidal activity was assayed against Echinococcus granulosus protoscolices. In total, 34 compounds were identified, accounting for 98.96% of the EO. The main compounds in the EO were cis-β-guaiene (34.2%), limonene (20.3%), borneol (11.6%), bornyl acetate (4.5%), β-cubebene (3.8%), sabinene (3.6%), phytol (3.1%), β-selinene (2.8%), camphene (2.2%), α-cubebene (2.4%), β-caryophyllene (1.9%), α-pinene (1.8%) and xanthinin (1.04%). The antibacterial and antifungal screening of the EO showed that all assayed concentrations significantly inhibited the growth of Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger (MIC = 0.5 ± 0.1, 1.3 ± 0.0, 4.8 ± 0.0, 20.5 ± 0.3, 55.2 ± 0.0 and 34.3 ± 0.0 µg/mL, respectively). The scolicidal assay indicated that the EO exhibited a significant activity against E. granulosus protoscolices. To the best of our knowledge, this is the first report on the scolicidal activity of X. strumarium. Because of the emergence of antimicrobial drug resistance, the study of new effective natural chemotherapeutic agents, such as the X. strumarium EO, possibly with low side effects, represents a very promising approach in biomedical research. Full article
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Review
Longevity Extension by Phytochemicals
by Anna Leonov, Anthony Arlia-Ciommo, Amanda Piano, Veronika Svistkova, Vicky Lutchman, Younes Medkour and Vladimir I. Titorenko
Molecules 2015, 20(4), 6544-6572; https://doi.org/10.3390/molecules20046544 - 13 Apr 2015
Cited by 76 | Viewed by 12823
Abstract
Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract [...] Read more.
Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract natural predators of such organisms, as well as lure pollinators and other symbiotes of these plants. In addition, many phytochemicals can extend longevity in heterotrophic organisms across phyla via evolutionarily conserved mechanisms. In this review, we discuss such mechanisms. We outline how structurally diverse phytochemicals modulate a complex network of signaling pathways that orchestrate a distinct set of longevity-defining cellular processes. This review also reflects on how the release of phytochemicals by plants into a natural ecosystem may create selective forces that drive the evolution of longevity regulation mechanisms in heterotrophic organisms inhabiting this ecosystem. We outline the most important unanswered questions and directions for future research in this vibrant and rapidly evolving field. Full article
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Review
Thapsigargin—From Thapsia L. to Mipsagargin
by Trine Bundgaard Andersen, Carmen Quiñonero López, Tom Manczak, Karen Martinez and Henrik Toft Simonsen
Molecules 2015, 20(4), 6113-6127; https://doi.org/10.3390/molecules20046113 - 08 Apr 2015
Cited by 81 | Viewed by 17732
Abstract
The sesquiterpene lactone thapsigargin is found in the plant Thapsia garganica L., and is one of the major constituents of the roots and fruits of this Mediterranean species. In 1978, the first pharmacological effects of thapsigargin were established and the full structure was [...] Read more.
The sesquiterpene lactone thapsigargin is found in the plant Thapsia garganica L., and is one of the major constituents of the roots and fruits of this Mediterranean species. In 1978, the first pharmacological effects of thapsigargin were established and the full structure was elucidated in 1985. Shortly after, the overall mechanism of the Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibition that leads to apoptosis was discovered. Thapsigargin has a potent antagonistic effect on the SERCA and is widely used to study Ca2+-signaling. The effect on SERCA has also been utilized in the treatment of solid tumors. A prodrug has been designed to target the blood vessels of cancer cells; the death of these blood vessels then leads to tumor necrosis. The first clinical trials of this drug were initiated in 2008, and the potent drug is expected to enter the market in the near future under the generic name Mipsagargin (G-202). This review will describe the discovery of the new drug, the on-going elucidation of the biosynthesis of thapsigargin in the plant and attempts to supply the global market with a novel potent anti-cancer drug. Full article
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Article
Comparison of Two Species of Notopterygium by GC-MS and HPLC
by Yaping Wang and Linfang Huang
Molecules 2015, 20(3), 5062-5073; https://doi.org/10.3390/molecules20035062 - 19 Mar 2015
Cited by 20 | Viewed by 8175
Abstract
Notopterygii Rhizoma et Radix (Qianghuo), including Notopterygium incisum Ting ex H. T. Chang (NI) and Notopterygium franchetii H. de Boiss (NF), is an important traditional Chinese medicine. Of these two plants, NI, is more commonly used and has a much higher price in [...] Read more.
Notopterygii Rhizoma et Radix (Qianghuo), including Notopterygium incisum Ting ex H. T. Chang (NI) and Notopterygium franchetii H. de Boiss (NF), is an important traditional Chinese medicine. Of these two plants, NI, is more commonly used and has a much higher price in the marketplace. To compare these two plants, a combination of gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) was carried out, thus obtaining an overall characterization for both volatile and none-volatile compounds. Combined with hierarchical cluster analysis (HCA) and principal component analysis, GC-MS was successfully applied to distinguish NF and NI. The chemical constitutes of volatile oil in NI and NF were firstly compared in detail, and 1R-alpha-pinene, beta-pinene and 4-isopropyl-1-methyl-1,4-cyclohexadiene had great contribution to the discrimination. Fingerprints of 14 batches of Qinghuo samples were also established based on HPLC, and an obvious difference was found between the two species. The chromatographic fingerprints were further analyzed by similarity analysis and HCA. The present study is the first reported evaluation of two origins of Notopterygii Rhizoma et Radix by GC-MS and HPLC, which will facilitate quality control and its clinical application. Full article
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868 KiB  
Article
Anti-Ageing Effects of Sonchus oleraceus L. (pūhā) Leaf Extracts on H2O2-Induced Cell Senescence
by Zong-Quan Ou, Thomas Rades and Arlene McDowell
Molecules 2015, 20(3), 4548-4564; https://doi.org/10.3390/molecules20034548 - 12 Mar 2015
Cited by 32 | Viewed by 7647
Abstract
Antioxidants protect against damage from free radicals and are believed to slow the ageing process. Previously, we have reported the high antioxidant activity of 70% methanolic Sonchus oleraceus L. (Asteraceae) leaf extracts. We hypothesize that S. oleraceus extracts protect cells against H2 [...] Read more.
Antioxidants protect against damage from free radicals and are believed to slow the ageing process. Previously, we have reported the high antioxidant activity of 70% methanolic Sonchus oleraceus L. (Asteraceae) leaf extracts. We hypothesize that S. oleraceus extracts protect cells against H2O2-induced senescence by mediating oxidative stress. Premature senescence of young WI-38 cells was induced by application of H2O2. Cells were treated with S. oleraceus extracts before or after H2O2 stress. The senescence- associated β-galactosidase (SA-β-gal) activity was used to indicate cell senescence. S. oleraceus extracts showed higher cellular antioxidant activity than chlorogenic acid in WI-38 cells. S. oleraceus extracts suppressed H2O2 stress-induced premature senescence in a concentration-dependent manner. At 5 and 20 mg/mL, S. oleraceus extracts showed better or equivalent effects of reducing stress-induced premature senescence than the corresponding ascorbic acid treatments. These findings indicate the potential of S. oleraceus extracts to be formulated as an anti-ageing agent. Full article
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830 KiB  
Article
Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption
by Hyang Yeon Kim, Mee Youn Lee, Hye Min Park, Yoo Kyoung Park, Jong Cheol Shon, Kwang-Hyeon Liu and Choong Hwan Lee
Molecules 2015, 20(2), 3107-3128; https://doi.org/10.3390/molecules20023107 - 13 Feb 2015
Cited by 34 | Viewed by 9824
Abstract
In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without [...] Read more.
In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling. Full article
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951 KiB  
Article
Promoting Effect of Foliage Sprayed Zinc Sulfate on Accumulation of Sugar and Phenolics in Berries of Vitis vinifera cv. Merlot Growing on Zinc Deficient Soil
by Chang-Zheng Song, Mei-Ying Liu, Jiang-Fei Meng, Ming Chi, Zhu-Mei Xi and Zhen-Wen Zhang
Molecules 2015, 20(2), 2536-2554; https://doi.org/10.3390/molecules20022536 - 02 Feb 2015
Cited by 71 | Viewed by 7462
Abstract
The effect of foliage sprayed zinc sulfate on berry development of Vitis vinifera cv. Merlot growing on arid zone Zn-deficient soils was investigated over two consecutive seasons, 2013 and 2014. Initial zinc concentration in soil and vines, photosynthesis at three berry developmental stages, [...] Read more.
The effect of foliage sprayed zinc sulfate on berry development of Vitis vinifera cv. Merlot growing on arid zone Zn-deficient soils was investigated over two consecutive seasons, 2013 and 2014. Initial zinc concentration in soil and vines, photosynthesis at three berry developmental stages, berry weight, content of total soluble solids, titratable acidity, phenolics and expression of phenolics biosynthetic pathway genes throughout the stages were measured. Foliage sprayed zinc sulfate showed promoting effects on photosynthesis and berry development of vines and the promotion mainly occurred from veraison to maturation. Zn treatments enhanced the accumulation of total soluble solids, total phenols, flavonoids, flavanols, tannins and anthocyanins in berry skin, decreasing the concentration of titratable acidity. Furthermore, foliage sprayed zinc sulfate could significantly influence the expression of phenolics biosynthetic pathway genes throughout berry development, and the results of expression analysis supported the promotion of Zn treatments on phenolics accumulation. This research is the first comprehensive and detailed study about the effect of foliage sprayed Zn fertilizer on grape berry development, phenolics accumulation and gene expression in berry skin, providing a basis for improving the quality of grape and wine in Zn-deficient areas. Full article
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909 KiB  
Article
Soy Isoflavones in Nutritionally Relevant Amounts Have Varied Nutrigenomic Effects on Adipose Tissue
by Elena Giordano, Alberto Dávalos, Maria Carmen Crespo, Joao Tomé-Carneiro, Diego Gómez-Coronado and Francesco Visioli
Molecules 2015, 20(2), 2310-2322; https://doi.org/10.3390/molecules20022310 - 30 Jan 2015
Cited by 14 | Viewed by 7596
Abstract
Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that [...] Read more.
Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that soy foods and supplements positively impact human health has become increasingly controversial among the general public because of the reported estrogenic activities of soy isoflavones. In this study, we investigated the nutrigenomic actions of soy isoflavones (in nutritionally-relevant amounts) with a specific focus on the adipose tissue, due to its pivotal role in cardiometabolism. Young C57BL/6 mice were maintained for eight weeks under two different diet regimes: (1) purified control diet; or (2) purified control diet supplemented with 0.45 g% soybean dry purified extract (a genistein/daidzein mix). Soy isoflavones increased plasma total cholesterol concentrations and decreased triglyceride ones. Circulating leptin levels was also increased by soy consumption. Differentially expressed genes in adipose tissue were classified according to their role(s) in cellular or metabolic pathways. Our data show that soy isoflavones, administered in nutritionally-relevant amounts, have diverse nutrigenomic effects on adipose tissue. Taking into account the moderate average exposure to such molecules, their impact on cardiovascular health needs to be further investigated to resolve the issue of whether soy consumption does indeed increase or decrease cardiovascular risk. Full article
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1351 KiB  
Article
The Content of Phenolic Compounds in Leaf Tissues of Aesculus glabra and Aesculus parviflora Walt.
by Jan Oszmiański, Joanna Kolniak-Ostek and Agata Biernat
Molecules 2015, 20(2), 2176-2189; https://doi.org/10.3390/molecules20022176 - 28 Jan 2015
Cited by 31 | Viewed by 7131
Abstract
In plants, flavonoids play an important role in biological processes. They are involved in UV-scavenging, fertility and disease resistance. Therefore, in this study, we attempted to quantify and characterize phenolic compounds in Aesculus parviflora Walt. leaves and Aesculus glabra leaves partly suffering from [...] Read more.
In plants, flavonoids play an important role in biological processes. They are involved in UV-scavenging, fertility and disease resistance. Therefore, in this study, we attempted to quantify and characterize phenolic compounds in Aesculus parviflora Walt. leaves and Aesculus glabra leaves partly suffering from attack by a leaf mining insect (C. ohridella). A total of 28 phenolic compounds belonging to the hydroxycinnamic acid, flavan-3-ols and flavonol groups were identified and quantified in Aesculus parviflora and A. glabra leaf extracts. Significantly decreased concentrations of some phenolic compounds, especially of flavan-3-ols, were observed in infected leaves compared to the non-infected ones. Additionally, a higher content of polymeric procyanidins in leaves of Aesculus parviflora than in Aesculus glabra may explain their greater resistance to C. ohridella insects. Full article
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706 KiB  
Review
Triterpenes as Potentially Cytotoxic Compounds
by Malwina Chudzik, Ilona Korzonek-Szlacheta and Wojciech Król
Molecules 2015, 20(1), 1610-1625; https://doi.org/10.3390/molecules20011610 - 19 Jan 2015
Cited by 145 | Viewed by 10269
Abstract
Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method [...] Read more.
Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method for treating cancer because of their cytotoxic properties and chemopreventive activities. Full article
1782 KiB  
Article
The Role of Selected Flavonols in Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor–1 (TRAIL-R1) Expression on Activated RAW 264.7 Macrophages
by Monika Warat, Tadeusz Sadowski, Ewelina Szliszka, Wojciech Król and Zenon P. Czuba
Molecules 2015, 20(1), 900-912; https://doi.org/10.3390/molecules20010900 - 08 Jan 2015
Cited by 9 | Viewed by 5405
Abstract
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptors (TRAIL-R) are an important factor of apoptosis in cancer cells. There are no data about the effect of flavonols on the receptor expression on a surface of macrophage like cells. In this study, the expression level of [...] Read more.
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptors (TRAIL-R) are an important factor of apoptosis in cancer cells. There are no data about the effect of flavonols on the receptor expression on a surface of macrophage like cells. In this study, the expression level of TRAIL-R1 on murine RAW264.7 macrophages in the presence of selected flavonols: galangin, kaempferol, kaempferide and quercetin, which differ from their phenyl ring substituents, were studied. The expression of TRAIL-R1 death receptors on non-stimulated and lipopolysaccharide (LPS)-stimulated macrophages was determined using flow cytometry. The results suggested that compounds being tested can modulate TRAIL-R1 expression and can enhance TRAIL-mediated apoptosis. Full article
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929 KiB  
Article
Pinelliae Rhizoma, a Toxic Chinese Herb, Can Significantly Inhibit CYP3A Activity in Rats
by Jinjun Wu, Zaixing Cheng, Shugui He, Jian Shi, Shuqiang Liu, Guiyu Zhang, Lijun Zhu, Liang Liu, Zhongqiu Liu, Na Lin and Linlin Lu
Molecules 2015, 20(1), 792-806; https://doi.org/10.3390/molecules20010792 - 07 Jan 2015
Cited by 14 | Viewed by 9148
Abstract
Raw Pinelliae Rhizoma (RPR) is a representative toxic herb that is widely used for eliminating phlegm or treating cough and vomiting. Given its irritant toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP) and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA), are [...] Read more.
Raw Pinelliae Rhizoma (RPR) is a representative toxic herb that is widely used for eliminating phlegm or treating cough and vomiting. Given its irritant toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP) and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA), are more commonly applied and administered concomitantly with other chemical drugs, such as cough medications. This study aimed to investigate the effects of RPR, PRP, and PRPZA on CYP3A activity. Testosterone (Tes) and buspirone (BP) were used as specific probe substrates ex vivo and in vivo, respectively. CYP3A activity was determined by the metabolite formation ratios from the substrates. Ex vivo results show that the metabolite formation ratios from Tes significantly decreased, indicating that RPR, PRP, and PRPZA could inhibit CYP3A activity in rats. CYP3A protein and mRNA levels were determined to explore the underlying mechanism. These levels showed marked and consistent down-regulation with CYP3A activity. A significant decrease in metabolite formation ratios from BP was also found in PRPZA group in vivo, implying that PRPZA could inhibit CYP3A activity. Conclusively, co-administration of PR with other CYP3A-metabolizing drugs may cause drug–drug interactions. Clinical use of PR-related formulae should be monitored carefully to avoid adverse interactions. Full article
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2014

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708 KiB  
Article
Stem Bark Extract and Fraction of Persea americana (Mill.) Exhibits Bactericidal Activities against Strains of Bacillus cereus Associated with Food Poisoning
by David A. Akinpelu, Olayinka A. Aiyegoro, Oluseun F. Akinpelu and Anthony I. Okoh
Molecules 2015, 20(1), 416-429; https://doi.org/10.3390/molecules20010416 - 30 Dec 2014
Cited by 23 | Viewed by 7674
Abstract
The study investigates the in vitro antibacterial potentials of stem bark extracts of Persea americana on strains of Bacillus cereus implicated in food poisoning. The crude stem bark extracts and butanolic fraction at a concentration of 25 mg/mL and 10 mg/mL, respectively, exhibited [...] Read more.
The study investigates the in vitro antibacterial potentials of stem bark extracts of Persea americana on strains of Bacillus cereus implicated in food poisoning. The crude stem bark extracts and butanolic fraction at a concentration of 25 mg/mL and 10 mg/mL, respectively, exhibited antibacterial activities against test isolates. The zones of inhibition exhibited by the crude extract and the fraction ranged between 10 mm and 26 mm, while the minimum inhibitory concentration values ranged between 0.78 and 5.00 mg/mL. The minimum bactericidal concentrations ranged between 3.12 mg/mL–12.5 mg/mL and 1.25–10 mg/mL for the extract and the fraction, respectively. The butanolic fraction killed 91.49% of the test isolates at a concentration of 2× MIC after 60 min of contact time, while a 100% killing was achieved after the test bacterial cells were exposed to the butanolic fraction at a concentration of 3× MIC after 90 min contact time. Intracellular protein and potassium ion leaked out of the test bacterial cells when exposed to certain concentrations of the fraction; this is an indication of bacterial cell wall disruptions by the extract’s butanolic fraction and, thus, caused a biocidal effect on the cells, as evident in the killing rate test results. Full article
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3960 KiB  
Article
Ag+ as a More Effective Elicitor for Production of Tanshinones than Phenolic Acids in Salvia miltiorrhiza Hairy Roots
by Bingcong Xing, Dongfeng Yang, Wanli Guo, Zongsuo Liang, Xijun Yan, Yonghong Zhu and Yan Liu
Molecules 2015, 20(1), 309-324; https://doi.org/10.3390/molecules20010309 - 24 Dec 2014
Cited by 73 | Viewed by 8883
Abstract
Phenolic acids and tanshinones are two groups of bioactive ingredients in Salvia miltiorrhiza Bunge. As a heavy metal elicitor, it has been reported that Ag+ can induce accumulations of both phenolic acids and tanshinones in S. miltiorrhiza hairy roots. In this study, [...] Read more.
Phenolic acids and tanshinones are two groups of bioactive ingredients in Salvia miltiorrhiza Bunge. As a heavy metal elicitor, it has been reported that Ag+ can induce accumulations of both phenolic acids and tanshinones in S. miltiorrhiza hairy roots. In this study, the effects of Ag+ treatment on accumulations of six phenolic acids and four tanshinones in S. miltiorrhiza hairy roots were investigated. To further elucidate the molecular mechanism, expressions of key genes involved in the biosynthesis of these ingredients were also detected. The results showed that although the total phenolic acids content was almost not affected by Ag+, accumulations of rosmarinic acid (RA), caffeic acid and ferulic acid were significantly increased, while accumulations of salvianolic acid B (LAB), danshensu (DSU) and cinnamic acid were decreased. We speculate that LAB probably derived from the branch pathway of DSU biosynthesis. Contents of four tanshinones were enhanced by Ag+ and their accumulations were more sensitive to Ag+ than phenolic acids. Genes in the upstream biosynthetic pathways of these ingredients responded to Ag+ earlier than those in the downstream biosynthetic pathways. Ag+ probably induced the whole pathways, upregulated gene expressions from the upstream pathways to the downstream pathways, and finally resulted in the enhancement of ingredient production. Compared with phenolic acids, tanshinone production was more sensitive to Ag+ treatments. This study will help us understand how secondary metabolism in S. miltiorrhiza responds to elicitors and provide a reference for the improvement of the production of targeted compounds in the near future. Full article
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2539 KiB  
Article
In Silico Affinity Profiling of Neuroactive Polyphenols for Post-Traumatic Calpain Inactivation: A Molecular Docking and Atomistic Simulation Sensitivity Analysis
by Pradeep Kumar, Yahya E. Choonara and Viness Pillay
Molecules 2015, 20(1), 135-168; https://doi.org/10.3390/molecules20010135 - 23 Dec 2014
Cited by 18 | Viewed by 6987
Abstract
Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation [...] Read more.
Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain’s proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM), molecular dynamics (MD), and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin) and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM) demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain–calpain inhibitor molecular complexes’ energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies. Full article
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740 KiB  
Article
Chemical Composition, Antibacterial and Antioxidant Activities of Six Essentials Oils from the Alliaceae Family
by Dima Mnayer, Anne-Sylvie Fabiano-Tixier, Emmanuel Petitcolas, Tayssir Hamieh, Nancy Nehme, Christine Ferrant, Xavier Fernandez and Farid Chemat
Molecules 2014, 19(12), 20034-20053; https://doi.org/10.3390/molecules191220034 - 01 Dec 2014
Cited by 166 | Viewed by 16981
Abstract
Six essential oils (EOs) from the Alliaceae family, namely garlic (Allium sativum), onion (Allium cepa), leek (Allium porrum), Chinese chive (Allium tuberosum), shallot (Allium ascalonicum) and chive (Allium schoenoprasum) were characterized by GC [...] Read more.
Six essential oils (EOs) from the Alliaceae family, namely garlic (Allium sativum), onion (Allium cepa), leek (Allium porrum), Chinese chive (Allium tuberosum), shallot (Allium ascalonicum) and chive (Allium schoenoprasum) were characterized by GC and GC-MS and evaluated for their functional food properties. Antibacterial properties were tested on five food-borne pathogens: Two Gram-positive Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 19115) and three Gram-negative Salmonella Typhimurium (ATCC 14028), Escherichia coli (ATCC 8739) and Campylobacter jejuni (ATCC 33291) bacteria. Antioxidant and radical-scavenging properties were tested by means of Folin-Ciocalteu and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. Garlic, Chinese chive and onion EOs had the highest antibacterial activity whereas shallot and leek EOs were the strongest antioxidants. Heating caused a decrease in the antioxidant activity of these Eos, as shown in the Total Polar Materials (TPM) test. Suggestions on relationships between chemical composition and biological activities are presented. Results show that the EOs could be of value in the food industry as alternatives to synthetic antioxidants. Full article
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605 KiB  
Review
Recent Advances in the Chemical Composition of Propolis
by Shuai Huang, Cui-Ping Zhang, Kai Wang, George Q. Li and Fu-Liang Hu
Molecules 2014, 19(12), 19610-19632; https://doi.org/10.3390/molecules191219610 - 26 Nov 2014
Cited by 514 | Viewed by 27519
Abstract
Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such [...] Read more.
Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such diverse chemical classes as flavonoids, phenylpropanoids, terpenenes, stilbenes, lignans, coumarins, and their prenylated derivatives, showing a pattern consistent with around 300 previously reported compounds. The chemical characteristics of propolis are linked to the diversity of geographical location, plant sources and bee species. Full article
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253 KiB  
Article
Evaluation of the Chemical and Antioxidant Properties of Wild and Cultivated Mushrooms of Ghana
by Mary Obodai, Isabel C.F.R. Ferreira, Ângela Fernandes, Lillian Barros, Deborah L. Narh Mensah, Matilda Dzomeku, Arailde F. Urben, Juanita Prempeh and Richard K. Takli
Molecules 2014, 19(12), 19532-19548; https://doi.org/10.3390/molecules191219532 - 26 Nov 2014
Cited by 61 | Viewed by 7382
Abstract
Knowledge of the chemical composition of both wild and cultivated edible mushrooms in Ghana is limited. This study reports their nutritional value, composition in lipophilic and hydrophilic molecules, minerals and antioxidant properties. The samples were found to be nutritionally rich in carbohydrates, ranging [...] Read more.
Knowledge of the chemical composition of both wild and cultivated edible mushrooms in Ghana is limited. This study reports their nutritional value, composition in lipophilic and hydrophilic molecules, minerals and antioxidant properties. The samples were found to be nutritionally rich in carbohydrates, ranging from 64.14 ± 0.93 g in Pleurotus ostreatus strain EM-1 to 80.17 ± 0.34 g in Lentinus squarrosulus strain LSF. The highest level of proteins (28.40 ± 0.86 g) was recorded in the mentioned P. ostreatus strain. Low fat contents were registered in the samples, with Auricularia auricula recording the lowest value. High levels of potassium were also observed with the following decreasing order of elements: K > P ~ Na > Mg > Ca. High levels of antioxidants were also observed, thus making mushrooms suitable to be used as functional foods or nutraceutical sources. Furthermore, this study provides new information regarding chemical properties of mushrooms from Ghana, which is very important for the biodiversity characterization of this country. Full article
477 KiB  
Article
Method Development and Validation for Pharmacokinetic and Tissue Distributions of Ellagic Acid Using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS)
by Linlin Yan, Peipei Yin, Chao Ma and Yujun Liu
Molecules 2014, 19(11), 18923-18935; https://doi.org/10.3390/molecules191118923 - 18 Nov 2014
Cited by 47 | Viewed by 10127
Abstract
Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A [...] Read more.
Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A simple, rapid, sensitive and specific liquid chromatography–tandem mass spectrometry method to determine the ellagic acid in plasma and tissue samples was developed and validated. The separation was achieved using reversed-phase ultra-performance liquid chromatography (UPLC), and the mass spectrometric detection was achieved using heated electrospray ionization (negative mode) and multiple ion monitoring (m/z 301/229). A sample cleanup with a solid phase extraction (SPE) step prior to the UPLC-MS/MS analysis was also developed. The SPE and UPLC-MS/MS method established here was successfully applied to reveal the pharmacokinetic profiles and tissue distribution of ellagic acid. After oral administration dosing at 50 mg/kg, plasma levels of ellagic acid peaked at about 0.5 h, with Cmax value of 93.6 ng/mL, and the results showed that the ellagic acid was poorly absorbed after oral administration. The pharmacokinetic profile of ellagic acid fitted to a two-compartment model with t1/2α 0.25 h and t1/2β 6.86 h, respectively. Following oral administration, ellagic acid was detected in all examined tissues including kidney, liver, heart, lung and brain et al., and the highest levels were found in kidney and liver. Full article
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427 KiB  
Article
Profiling the Metabolism of Astragaloside IV by Ultra Performance Liquid Chromatography Coupled with Quadrupole/Time-of-Flight Mass Spectrometry
by Xu-Dong Cheng and Ming-Gang Wei
Molecules 2014, 19(11), 18881-18896; https://doi.org/10.3390/molecules191118881 - 17 Nov 2014
Cited by 23 | Viewed by 7481
Abstract
Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological [...] Read more.
Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological actions and pharmacology. In the present study, an ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)-based approach was developed to profile the metabolites of astragaloside IV in rat plasma, bile, urine and feces samples. Twenty-two major metabolites were detected. The major components found in plasma, bile, urine and feces included the parent chemical and phases I and II metabolites. The major metabolic reactions of astragaloside IV were hydrolysis, glucuronidation, sulfation and dehydrogenation. These results will help to improve understanding the metabolism and reveal the biotransformation profiling of astragaloside IV in vivo. The metabolic information obtained from our study will guide studies into the pharmacological activity and clinical safety of astragaloside IV. Full article
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