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23 pages, 5061 KiB

Open AccessArticle

Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers

by Oluwafemi Adeleke Ojo, Akingbolabo Daniel Ogunlakin, Rotdelmwa Filibis Maimako, Gideon Ampoma Gyebi, Christopher Busayo Olowosoke, Odunayo Anthonia Taiwo, Tobiloba Christiana Elebiyo, David Adeniyi, Bolaji David, Matthew Iyobhebhe, Juliana Bunmi Adetunji, Damilare IyinKristi Ayokunle, Adebola Busola Ojo, Ramzi A. Mothana and Abdullah R. Alanzi

Molecules 2023, 28(21), 7425; https://doi.org/10.3390/molecules28217425 - 04 Nov 2023

Viewed by 761

Abstract

This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe²⁺-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of [...] Read more.

This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe²⁺-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of cellular signals is speculated upon to proffer suitable therapeutics for metabolic stress disorder upon their inhibition. While we know little about therapeutics with flexible dual inhibitors for these protein targets, this study was designed to screen KAD-7’s (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) inhibitory potential for both protein targets. We induced oxidative hepatic damage via the incubation of hepatic tissue supernatant with 0.1 mM FeSO₄ for 30 min at 37 °C. We achieved the treatment by incubating the hepatic tissues with KAD-7 under the same conditions. The catalase (CAT), glutathione (GSH), malondialdehyde (MDA), ATPase, and ENTPDase activity were all measured in the tissues. We predicted how the drug candidate would work against ATPase and ENTPDase targets using molecular methods. When hepatic injury was induced, there was a significant decrease in the levels of the GSH, CAT, and ENTPDase (p < 0.05) activities. In contrast, we found a noticeable rise in the MDA levels and ATPase activity. KAD-7 therapy resulted in lower levels of these activities overall (p < 0.05), as compared to the control levels. We found the compound to have a strong affinity for ATPase (−7.1 kcal/mol) and ENTPDase (−7.4 kcal/mol), and a better chemical reactivity than quercetin. It also met all drug-likeness parameters. Our study shows that KAD-7 can protect the liver from damage caused by FeSO₄ by reducing oxidative stress and purinergic actions. Our studies indicate that KAD-7 could be developed as a therapeutic option since it can flexibly inhibit both ATPase and ENTPDase. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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17 pages, 3953 KiB

Open AccessArticle

Chemical Profiling and Biological Activity of Psydrax dicoccos Gaertn

by Kamaraj Veeramuthu, Vishal Ahuja, Pushparaj Annadurai, Daniel A. Gideon, Balamurugan Sundarrajan, Marius Emil Rusu, Vinothkanna Annadurai and Kandavel Dhandayuthapani

Molecules 2023, 28(20), 7101; https://doi.org/10.3390/molecules28207101 - 15 Oct 2023

Viewed by 1241

Abstract

Breast cancer is one of the deadliest diseases in women with a mortality rate of 6.6%. Adverse effects of synthetic drugs have directed research toward safer alternatives such as natural compounds. This study focused on Psydrax dicoccos Gaertn, an evergreen tree abundantly distributed [...] Read more.

Breast cancer is one of the deadliest diseases in women with a mortality rate of 6.6%. Adverse effects of synthetic drugs have directed research toward safer alternatives such as natural compounds. This study focused on Psydrax dicoccos Gaertn, an evergreen tree abundantly distributed in Tamil Nadu (India) for its possible application against breast cancer cells. P. dicoccos leaf methanol extract, found within a wide range of phytochemicals, demonstrated cytotoxic effects against MCF7 breast cancer cells at IC₅₀ of 34 μg/mL. The extract exhibited good antioxidant activities against DPPH^• (62%) and ABTS^•+ (80%), as well as concentration-dependent (100–800 μg/mL) anti-inflammatory potential of 18–60% compared to standards, ascorbic acid or aspirin, respectively. Moreover, even low extract concentrations (10 μg/mL) inhibited the growth of Escherichia coli (1.9 ± 0.6 mm) and Pseudomonas aeruginosa (2.3 ± 0.7 mm), thus showing high antimicrobial and anti-inflammatory potential. GC-MS and LC-MS analyses identified 31 and 16 components, respectively, of which selected compounds were used to evaluate the interaction between key receptors (AKT-1, COX-2, and HER-2) of breast cancer based on binding energy (ΔG) and inhibition constant (K_i). The results indicate that bioactive compounds from P. dicoccos have potential against breast cancer cells, but further evaluations are needed. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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14 pages, 4285 KiB

Open AccessArticle

Preventing Adipogenesis and Preserving Mitochondria and GLUT-4 Functions by Extracts and Isolated Compounds of Australian Acacia saligna

by Anjar P. Asmara, Hui Chen and Alison T. Ung

Molecules 2023, 28(18), 6677; https://doi.org/10.3390/molecules28186677 - 18 Sep 2023

Viewed by 894

Abstract

Acacia saligna’s secondary metabolites show promise in treating type 2 diabetes mellitus and its related conditions. We previously discovered that methanolic extracts, isolated flavonoids, and cyclitols effectively preserve mitochondria in 3T3-L1 adipocytes. In this current work, quantification of lipid droplet levels with [...] Read more.

Acacia saligna’s secondary metabolites show promise in treating type 2 diabetes mellitus and its related conditions. We previously discovered that methanolic extracts, isolated flavonoids, and cyclitols effectively preserve mitochondria in 3T3-L1 adipocytes. In this current work, quantification of lipid droplet levels with Oil Red O assay showed a noticeable decrease in lipogenesis in 3T3-L1 cells. Methanolic leaf and bark extracts and isolated compounds, (−)-epicatechin 6 and myricitrin 8, reduced cellular lipid levels by 21.15% to 25.28%, respectively. mRNA levels of key regulators of mitochondrial biogenesis, such as adiponectin, PGC-1α, and mtTFA, were increased. Methanolic flower extract (FL-MeOH) and its chemical components, naringenin 1 and D-(+)-pinitol 5a, increased these gene levels from 10% to 29% at the higher dose. Our study found that FL-MeOH slightly reduced pro-inflammatory cytokines TNF-α and IL-6, attributed to two phytochemicals, naringenin-7-O-α-L-arabinofuranoside 2 and D-(+)-pinitol 5a. Western blot analysis also showed that adipocytes treated with MeOH extracts had higher GLUT-4 expression levels than untreated adipocytes. Overall, A. saligna extracts and their isolated compounds demonstrated anti-lipogenesis activity during 3T3-L1 cell differentiation, modulation of transcriptional levels of adiponectin, PGC-1α, and mtTFA, reducing TNF-α and IL-6 mRNA levels, promoting mitochondrial biogenesis, and enhancing GLUT-4 expression. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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23 pages, 7353 KiB

Open AccessArticle

Resveratrol Mitigates Bisphenol A-Induced Metabolic Disruptions: Insights from Experimental Studies

by Muhammad Sajid Hamid Akash, Mutayyba Fatima, Kanwal Rehman, Qudsia Rehman, Zunera Chauhdary, Ahmed Nadeem and Tahir Maqbool Mir

Molecules 2023, 28(15), 5865; https://doi.org/10.3390/molecules28155865 - 03 Aug 2023

Cited by 3 | Viewed by 1082

Abstract

The aim of this study was to investigate the disruptions of metabolic pathways induced by bisphenol A (BPA) and explore the potential therapeutic intervention provided by resveratrol (RSV) in mitigating these disruptions through the modulation of biochemical pathways. Wistar albino rats were divided [...] Read more.

The aim of this study was to investigate the disruptions of metabolic pathways induced by bisphenol A (BPA) and explore the potential therapeutic intervention provided by resveratrol (RSV) in mitigating these disruptions through the modulation of biochemical pathways. Wistar albino rats were divided into three groups: group 1 served as the control, group 2 received 70 mg/Kg of BPA, and group 3 received 70 mg/kg of BPA along with 100 mg/Kg of RSV. After the treatment period, various biomarkers and gene expressions were measured to assess the effects of BPA and the potential protective effects of RSV. The results revealed that BPA exposure significantly increased the serum levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines such as TNF-α and IL-6. Concurrently, BPA exposure led to a reduction in the levels of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as GLUT4 and HDL cholesterol. However, the administration of RSV along with BPA significantly ameliorated these alterations in the biomarker levels induced through BPA exposure. RSV treatment effectively reduced the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines, while increasing the levels of antioxidant enzymes, GLUT4, and HDL cholesterol. Furthermore, BPA exposure suppressed the mRNA expression of glucokinase (GCK), insulin-like growth factor 1 (IGF-1), and glucose transporter 2 (GLUT2) and up-regulated the mRNA expression of uncoupling protein 2 (UCP2), which are all critical biomarkers involved in glucose metabolism and insulin regulation. In contrast, RSV treatment effectively restored the altered mRNA expressions of these biomarkers, indicating its potential to modulate transcriptional pathways and restore normal metabolic function. In conclusion, the findings of this study strongly suggest that RSV holds promise as a therapeutic intervention for BPA-induced metabolic disorders. By mitigating the disruptions in various metabolic pathways and modulating gene expressions related to glucose metabolism and insulin regulation, RSV shows potential in restoring normal metabolic function and counteracting the adverse effects induced by BPA exposure. However, further research is necessary to fully understand the underlying mechanisms and optimize the dosage and duration of RSV treatment for maximum therapeutic benefits. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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10 pages, 1178 KiB

Open AccessArticle

Antioxidant Activities of Essential Oils and Their Major Components in Scavenging Free Radicals, Inhibiting Lipid Oxidation and Reducing Cellular Oxidative Stress

by Xiaohua Chen, Shufeng Shang, Fei Yan, Hai Jiang, Guanjie Zhao, Shan Tian, Rui Chen, Dejing Chen and Yafeng Dang

Molecules 2023, 28(11), 4559; https://doi.org/10.3390/molecules28114559 - 05 Jun 2023

Cited by 13 | Viewed by 2806

Abstract

Antioxidant activities of five essential oils (cinnamon, thyme, clove, lavender and peppermint oils) and their major components (eugenol, thymol, linalool, and menthol) were evaluated on scavenging DPPH (2,2-diphenyl-1 picrylhydrazyl) free radicals, inhibiting polyunsaturated fatty acid oxidation in fish oil emulsion (FOE), and reducing [...] Read more.

Antioxidant activities of five essential oils (cinnamon, thyme, clove, lavender and peppermint oils) and their major components (eugenol, thymol, linalool, and menthol) were evaluated on scavenging DPPH (2,2-diphenyl-1 picrylhydrazyl) free radicals, inhibiting polyunsaturated fatty acid oxidation in fish oil emulsion (FOE), and reducing oxidative stress in human red blood cells (RBC). The essential oils from cinnamon, thyme, clove and their main components, eugenol and thymol, exhibited the highest antioxidant activity in the FOE and RBC systems. It was found that the antioxidant activity of essential oils was positively correlated to the content of eugenol and thymol, while lavender and peppermint oils and their main components, linalool and menthol, had very low antioxidant activity. Compared with scavenging DPPH free radical activity, the antioxidant activity in FOE and RBC systems could better reflect the actual antioxidant potential of essential oil in preventing lipid oxidation and reducing oxidative stress in biological system. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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18 pages, 7057 KiB

Open AccessArticle

Antihyperglycemic Properties of Extracts and Isolated Compounds from Australian Acacia saligna on 3T3-L1 Adipocytes

by Anjar P. Asmara, Anchalee Prasansuklab, Anchalee Chiabchalard, Hui Chen and Alison T. Ung

Molecules 2023, 28(10), 4054; https://doi.org/10.3390/molecules28104054 - 12 May 2023

Cited by 1 | Viewed by 1261

Abstract

Our early work indicated that methanolic extracts from the flowers, leaves, bark, and isolated compounds of Acacia saligna exhibited significant antioxidant activities in vitro. The overproduction of reactive oxygen species (ROS) in the mitochondria (mt-ROS) interfered with glucose uptake, metabolism, and its AMPK-dependent [...] Read more.

Our early work indicated that methanolic extracts from the flowers, leaves, bark, and isolated compounds of Acacia saligna exhibited significant antioxidant activities in vitro. The overproduction of reactive oxygen species (ROS) in the mitochondria (mt-ROS) interfered with glucose uptake, metabolism, and its AMPK-dependent pathway, contributing to hyperglycemia and diabetes. This study aimed to screen the ability of these extracts and isolated compounds to attenuate the production of ROS and maintain mitochondrial function via the restoration of mitochondrial membrane potential (MMP) in 3T3-L1 adipocytes. Downstream effects were investigated via an immunoblot analysis of the AMPK signalling pathway and glucose uptake assays. All methanolic extracts effectively reduced cellular ROS and mt-ROS levels, restored the MMP, activated AMPK-α, and enhanced cellular glucose uptake. At 10 µM, (−)-epicatechin-6 (from methanolic leaf and bark extracts) markedly reduced ROS and mt-ROS levels by almost 30% and 50%, respectively, with an MMP potential ratio 2.2-fold higher compared to the vehicle control. (−)-Epicatechin 6 increased the phosphorylation of AMPK-α by 43%, with an 88% higher glucose uptake than the control. Other isolated compounds include naringenin 1, naringenin-7-O-α-L-arabinopyranoside 2, isosalipurposide 3, D-(+)-pinitol 5a, and (−)-pinitol 5b, which also performed relatively well across all assays. Australian A. saligna active extracts and compounds can reduce ROS oxidative stress, improve mitochondrial function, and enhance glucose uptake through AMPK-α activation in adipocytes, supporting its potential antidiabetic application. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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16 pages, 4475 KiB

Open AccessArticle

The Antimicrobial Peptide γ-Thionin from Habanero Chile (Capsicum chinense) Induces Caspase-Independent Apoptosis on Human K562 Chronic Myeloid Leukemia Cells and Regulates Epigenetic Marks

by Luis José Flores-Alvarez, Paola Jiménez-Alcántar, Alejandra Ochoa-Zarzosa and Joel E. López-Meza

Molecules 2023, 28(9), 3661; https://doi.org/10.3390/molecules28093661 - 23 Apr 2023

Viewed by 1392

Abstract

Cancer is a relevant health problem worldwide. In 2020, leukemias represented the 13th most commonly reported cancer cases worldwide but the 10th most likely to cause deaths. There has been a progressive increase in the efficacy of treatments for leukemias; however, these still [...] Read more.

Cancer is a relevant health problem worldwide. In 2020, leukemias represented the 13th most commonly reported cancer cases worldwide but the 10th most likely to cause deaths. There has been a progressive increase in the efficacy of treatments for leukemias; however, these still generate important side effects, so it is imperative to search for new alternatives. Defensins are a group of antimicrobial peptides with activity against cancer cells. However, the cytotoxic mechanism of these peptides has been described mainly for animal defensins. This study shows that defensin γ-thionin (Capsicum chinense) is cytotoxic to the K562 leukemia cells with an IC₅₀ = 290 μg/mL (50.26 μM) but not for human peripheral blood mononuclear cells. Results showed that γ-thionin did not affect the membrane potential; however, the peptide modified the mitochondrial membrane potential (ΔΨm) and the intracellular calcium release. In addition, γ-thionin induced apoptosis in K562 cells, but the activation of caspases 8 and 9 was not detected. Moreover, the activation of calpains was detected at one hour of treatment, suggesting that γ-thionin activates the caspase-independent apoptosis. Furthermore, the γ-thionin induced epigenetic modifications on histone 3 in K562 cells, increased global acetylation (~2-fold), and specific acetylation marks at lysine 9 (H3K9Ac) (~1.5-fold). In addition, γ-thionin increased the lysine 9 methylation (H3K9me) and dimethylation marks (H3K9me2) (~2-fold), as well as the trimethylation mark (H3K9me3) (~2-fold). To our knowledge, this is the first report of a defensin that triggers caspase-independent apoptosis in cancer cells via calpains and regulating chromatin remodelation, a novel property for a plant defensin. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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14 pages, 2370 KiB

Open AccessFeature PaperArticle

Chondroitin Sulfate from Oreochromis niloticus Waste Reduces Leukocyte Influx in an Acute Peritonitis Model

by Marianna Barros Silva, Lívia de Lourdes de Sousa Pinto, Luiz Henrique Medeiros, Airton Araújo Souza, Jr., Suely Ferreira Chavante, Luciana Guimarães Alves Filgueira, Rafael Barros Gomes Camara, Guilherme Lanzi Sassaki, Hugo Alexandre Oliveira Rocha and Giulianna Paiva Viana Andrade

Molecules 2023, 28(7), 3082; https://doi.org/10.3390/molecules28073082 - 30 Mar 2023

Viewed by 1381

Abstract

Oreochromis niloticus (tilapia) is one of the most cultivated fish species worldwide. Tilapia farming generates organic waste from fish removal processes in nurseries. Visceral waste can damage natural ecosystems. Therefore, the use of this material as a source of biomolecules helps reduce environmental [...] Read more.

Oreochromis niloticus (tilapia) is one of the most cultivated fish species worldwide. Tilapia farming generates organic waste from fish removal processes in nurseries. Visceral waste can damage natural ecosystems. Therefore, the use of this material as a source of biomolecules helps reduce environmental impacts and improve pharmacological studies. Tilapia viscera were subjected to proteolysis and complexation with an ion-exchange resin. The obtained glycosaminoglycans were purified using ion exchange chromatography (DEAE-Sephacel). The electrophoretic profile and analysis of 1H/13C nuclear magnetic resonance (NMR) spectra allowed for the characterization of the compound as chondroitin sulfate and its sulfation position. This chondroitin was named CST. We tested the ability of CST to reduce leukocyte influx in acute peritonitis models induced by sodium thioglycolate and found a significant reduction in leukocyte migration to the peritoneal cavity, similar to the polymorphonuclear population of the three tested doses of CST. This study shows, for the first time, the potential of CST obtained from O. niloticus waste as an anti-inflammatory drug, thereby contributing to the expansion of the study of molecules with pharmacological functions. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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20 pages, 2482 KiB

Open AccessArticle

Identification of Phytochemicals in Bioactive Extracts of Acacia saligna Growing in Australia

by Anjar P. Asmara, Anchalee Prasansuklab, Tewin Tencomnao and Alison T. Ung

Molecules 2023, 28(3), 1028; https://doi.org/10.3390/molecules28031028 - 19 Jan 2023

Cited by 3 | Viewed by 1995

Abstract

Acacia saligna growing in Australia has not been fully investigated for its bioactive phytochemicals. Sequential polarity-based extraction was employed to provide four different extracts from individual parts of A. saligna. Bioactive extracts were determined using in vitro antioxidant and yeast α-glucosidase inhibitory [...] Read more.

Acacia saligna growing in Australia has not been fully investigated for its bioactive phytochemicals. Sequential polarity-based extraction was employed to provide four different extracts from individual parts of A. saligna. Bioactive extracts were determined using in vitro antioxidant and yeast α-glucosidase inhibitory assays. Methanolic extracts from barks, leaves, and flowers are the most active and have no toxicity against 3T3-L1 adipocytes. Compound isolation of bioactive extracts provided us with ten compounds. Among them are two novel natural products; naringenin-7-O-α-L-arabinopyranoside 2 and (3S*,5S*)-3-hydroxy-5-(2-aminoethyl) dihydrofuran-2(3H)-one 9. D-(+)-pinitol 5a (from barks and flowers), (−)-pinitol 5b (exclusively from leaf), and 2,4-di-t-butylphenol 7 are known natural products and new to A. saligna. (−)-Epicatechin 6, quercitrin 4, and myricitrin 8 showed potent antioxidant activities consistently in DPPH and ABTS assays. (−)-Epicatechin 6 (IC₅₀ = 63.58 μM),D-(+)-pinitol 5a (IC₅₀ = 74.69 μM), and naringenin 1 (IC₅₀ = 89.71 μM) are the strong inhibitors against the α-glucosidase enzyme. The presence of these compounds supports the activities exerted in our methanolic extracts. The presence of 2,4-di-t-butylphenol 7 may support the reported allelopathic and antifungal activities. The outcome of this study indicates the potential of Australian A. saligna as a rich source of bioactive compounds for drug discovery targeting type 2 diabetes. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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10 pages, 2810 KiB

Open AccessArticle

Discovery of Natural Small Molecules Promoting Collagen Secretion by High-Throughput Screening in Caenorhabditis elegans

by Jinyang Fang, Xinyue Wu, Xi’nan Meng, Dejin Xun, Suhong Xu and Yi Wang

Molecules 2022, 27(23), 8361; https://doi.org/10.3390/molecules27238361 - 30 Nov 2022

Cited by 1 | Viewed by 1805

Abstract

Advancing approaches for drug screening are in great demand to explore natural small molecules that may play important roles in collagen biogenesis, secretion, and assembly, which may find novel lead compounds for treating collagen-related diseases or preventing skin aging. In this study, we [...] Read more.

Advancing approaches for drug screening are in great demand to explore natural small molecules that may play important roles in collagen biogenesis, secretion, and assembly, which may find novel lead compounds for treating collagen-related diseases or preventing skin aging. In this study, we generated a single copy insertion transgenic Pcol-19- COL-12::GFP Caenorhabditis elegans (C. elegans) strain to label epidermis collagen XII (COL-12), a cuticle structure component, and established an efficient high-content screening techniques to discover bioactive natural products in this worm strain through quantification of fluorescence imaging. We performed a preliminary screening of 614 compounds from the laboratory’s library of natural small molecule compounds on the COL-12 labeling worm model, which was tested once at a single concentration of 100 µM to screen for compounds that promoted COL-12 protein amount. Besides col-12, the transcriptional levels of worm-associated collagen coding genes col-19 and sqt-3 were also examined, and none of the compounds affected their transcriptional levels. Meanwhile, the protein levels of COL-12 were significantly upregulated after treating with Danshensu, Lawsone, and Sanguinarine. The effects of these drugs on COL-12 overexpressing worms occur mainly after collagen transcription. Through various validation methods, Danshensu, Lawsone, and Sanguinarine were more effective in promoting the synthesis or secretion of COL-12. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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15 pages, 7736 KiB

Open AccessArticle

Isolation and In Silico Prediction of Potential Drug-like Compounds with a New Dimeric Prenylated Quinolone Alkaloid from Zanthoxylum rhetsa (Roxb.) Root Extracts Targeted against SARS-CoV-2 (Mpro)

by Fatema Tuz Zohora, A. T. M. Zafrul Azam, Sinthyia Ahmed, Khondaker Miraz Rahman, Mohammad A. Halim, Md. Rafi Anwar, Md. Hossain Sohrab, Fatema Tabassum, Choudhury Mahmood Hasan and Monira Ahsan

Molecules 2022, 27(23), 8191; https://doi.org/10.3390/molecules27238191 - 24 Nov 2022

Cited by 2 | Viewed by 1564

Abstract

A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of Zanthoxylum rhetsa, together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction [...] Read more.

A new dimeric prenylated quinolone alkaloid, named 2,11-didemethoxy-vepridimerine A, was isolated from the root bark of Zanthoxylum rhetsa, together with twelve known compounds. The structure of the new compound was elucidated on the basis of spectroscopic investigations (NMR and Mass). The interaction of the isolated compounds with the main protease of SARS-CoV-2 (Mpro) was evaluated using molecular docking followed by MD simulations. The result suggests that 2,11-didemethoxy-vepridimerine A, the new compound, has the highest negative binding affinity against the Mpro with a free energy of binding of −8.5 Kcal/mol, indicating interaction with the Mpro. This interaction was further validated by 100 ns MD simulation. This implies that the isolated new compound, which can be employed as a lead compound for an Mpro-targeting drug discovery program, may be able to block the action of Mpro. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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16 pages, 2781 KiB

Open AccessArticle

Antioxidant and Biological Activities of the Lotus Root Polysaccharide-Iron (III) Complex

by Shuai Yuan, Pei-Yu Dong, Hao-Hai Ma, Sheng-Lin Liang, Long Li and Xi-Feng Zhang

Molecules 2022, 27(20), 7106; https://doi.org/10.3390/molecules27207106 - 21 Oct 2022

Cited by 9 | Viewed by 1865

Abstract

In this study, the synthesis parameters of the lotus root polysaccharide iron complex (LRPF) were determined and optimized by response surface methodology. Under the optimum preparation conditions, the pH of the solution was 9, the ratio of M (trisodium citrate): m (lotus root [...] Read more.

In this study, the synthesis parameters of the lotus root polysaccharide iron complex (LRPF) were determined and optimized by response surface methodology. Under the optimum preparation conditions, the pH of the solution was 9, the ratio of M (trisodium citrate): m (lotus root polysaccharide) was 0.45, the reaction time was 3 h. UV spectroscopy, thermogravimetry, FT-IR spectroscopy, X-ray diffraction, CD, and NMR were used for the characterization of the LRPF. LRPF has good stability and easily releases iron ions under artificial gastrointestinal conditions. LRPF exhibited antioxidant activity in vitro and can significantly improve the antioxidant activity in vivo. In addition, LRPF has a good effect in the treatment of iron deficiency anemia in model mice, impacts the gut microbiome, and reduces the iron deficiency-induced perniciousness by regulating steroid hormone biosynthesis. Therefore, LRPF can be used as a nutritional supplement to treat and prevent iron-deficiency anemia and improve human immunity. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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15 pages, 1524 KiB

Open AccessArticle

C. spinosa L. subsp. rupestris Phytochemical Profile and Effect on Oxidative Stress in Normal and Cancer Cells

by Tiziana Bacchetti, Roberto Campagna, Davide Sartini, Monia Cecati, Camilla Morresi, Luisa Bellachioma, Erika Martinelli, Gabriele Rocchetti, Luigi Lucini, Gianna Ferretti and Monica Emanuelli

Molecules 2022, 27(19), 6488; https://doi.org/10.3390/molecules27196488 - 01 Oct 2022

Cited by 11 | Viewed by 2007

Abstract

Spices, widely used to improve the sensory characteristics of food, contain several bioactive compounds as well, including polyphenols, carotenoids, and glucosynolates. Acting through multiple pathways, these bioactive molecules affect a wide variety of cellular processes involved in molecular mechanisms important in the onset [...] Read more.

Spices, widely used to improve the sensory characteristics of food, contain several bioactive compounds as well, including polyphenols, carotenoids, and glucosynolates. Acting through multiple pathways, these bioactive molecules affect a wide variety of cellular processes involved in molecular mechanisms important in the onset and progress of human diseases. Capparis spinosa L. is an aromatic plant characteristic of the Mediterranean diet. Previous studies have reported that different parts (aerial parts, roots, and seeds) of C. spinosa exert various pharmacological activities. Flower buds of C. spinosa contain several bioactive compounds, including polyphenols and glucosinolates. Two different subspecies of C. spinosa L., namely, C. spinosa L. subsp. spinosa, and C. spinosa L. subsp. rupestris, have been reported. Few studies have been carried out in C. spinosa L. subsp. rupestris. The aim of our study was to investigate the phytochemical profile of floral buds of the less investigated species C. spinosa subsp. rupestris. Moreover, we investigated the effect of the extract from buds of C. spinosa subsp. rupestris (CSE) on cell proliferation, intracellular ROS levels, and expression of the antioxidant and anti-apoptotic enzyme paraoxonase-2 (PON2) in normal and cancer cells. T24 cells and Caco-2 cells were selected as models of advanced-stage human bladder cancer and human colorectal adenocarcinoma, respectively. The immortalized human urothelial cell line (UROtsa) and human dermal fibroblast (HuDe) were chosen as normal cell models. Through an untargeted metabolomic approach based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS), our results demonstrate that C. spinosa subsp. rupestris flower buds contain polyphenols and glucosinolates able to exert a higher cytotoxic effect and higher intracellular reactive oxygen species (ROS) production in cancer cells compared to normal cells. Moreover, upregulation of the expression of the enzyme PON2 was observed in cancer cells. In conclusion, our data demonstrate that normal and cancer cells are differentially sensitive to CSE, which has different effects on PON2 gene expression as well. The overexpression of PON2 in T24 cells treated with CSE could represent a mechanism by which tumor cells protect themselves from the apoptotic process induced by glucosinolates and polyphenols. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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7 pages, 1347 KiB

Open AccessArticle

The Luteolinidin and Petunidin 3-O-Glucoside: A Competitive Inhibitor of Tyrosinase

by Seo Young Yang, Jang Hoon Kim, Xiangdong Su and Jeong Ah Kim

Molecules 2022, 27(17), 5703; https://doi.org/10.3390/molecules27175703 - 04 Sep 2022

Cited by 2 | Viewed by 1623

Abstract

The enzyme tyrosinase plays a key role in the early stages of melanin biosynthesis. This study evaluated the inhibitory activity of anthocyanidin (1) and anthocyanins (2–6) on the catalytic reaction. Of the six derivatives examined, 1– [...] Read more.

The enzyme tyrosinase plays a key role in the early stages of melanin biosynthesis. This study evaluated the inhibitory activity of anthocyanidin (1) and anthocyanins (2–6) on the catalytic reaction. Of the six derivatives examined, 1–3 showed inhibitory activity with IC₅₀ values of 3.7 ± 0.1, 10.3 ± 1.0, and 41.3 ± 3.2 μM, respectively. Based on enzyme kinetics, 1–3 were confirmed to be competitive inhibitors with K_i values of 2.8, 9.0, and 51.9 μM, respectively. Molecular docking analysis revealed the formation of a binary encounter complex between 1–3 and the tyrosinase catalytic site. Luteolinidin (1) and petunidin 3-O-glucoside (2) may serve as tyrosinase inhibitors to block melanin production. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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16 pages, 1426 KiB

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Neurological Applications of Celery (Apium graveolens): A Scoping Review

by Terence Yew Chin Tan, Xin Yi Lim, Nor Azrina Norahmad, Hemahwathy Chanthira Kumar, Bee Ping Teh, Nai Ming Lai and Ami Fazlin Syed Mohamed

Molecules 2023, 28(15), 5824; https://doi.org/10.3390/molecules28155824 - 02 Aug 2023

Cited by 1 | Viewed by 2020

Abstract

Apium graveolens is an indigenous plant in the family Apiaceae, or Umbelliferae, that contains many active compounds. It has been used traditionally to treat arthritic conditions, gout, and urinary infections. The authors conducted a scoping review to assess the quality of available evidence [...] Read more.

Apium graveolens is an indigenous plant in the family Apiaceae, or Umbelliferae, that contains many active compounds. It has been used traditionally to treat arthritic conditions, gout, and urinary infections. The authors conducted a scoping review to assess the quality of available evidence on the overall effects of celery when treating neurological disorders. A systematic search was performed using predetermined keywords in selected electronic databases. The 26 articles included upon screening consisted of 19 in vivo studies, 1 published clinical trial, 4 in vitro studies and 2 studies comprising both in vivo and in vitro methods. A. graveolens and its bioactive phytoconstituent, 3-n-butylphthalide (NBP), have demonstrated their effect on neurological disorders such as Alzheimer’s disease, Parkinson’s disease, stroke-related neurological complications, depression, diabetes-related neurological complications, and epilepsy. The safety findings were minimal, showing that NBP is safe for up to 18 weeks at 15 mg/kg in animal studies, while there were adverse effects (7%) reported when consuming NBP for 24 weeks at 600 mg daily in human trials. In conclusion, the safety of A. graveolens extract and NBP can be further investigated clinically on different neurological disorders based on their potential role in different targeted pathways. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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29 pages, 2219 KiB

Open AccessReview

Bioactive Phytochemicals of Acacia saligna

by Alison T. Ung and Anjar P. Asmara

Molecules 2023, 28(11), 4396; https://doi.org/10.3390/molecules28114396 - 28 May 2023

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Abstract

Acacia saligna is native to Western Australia. It has become an introduced and fast-growing plant in other parts of the world due to its ability to adapt to drought, saline and alkaline soils, and hast growing environments. Studies on the bioactivities and phytochemicals [...] Read more.

Acacia saligna is native to Western Australia. It has become an introduced and fast-growing plant in other parts of the world due to its ability to adapt to drought, saline and alkaline soils, and hast growing environments. Studies on the bioactivities and phytochemicals of the plant extracts were conducted. However, comprehensive information that links those bioactivities to the identified compounds in the plant’s extracts is still lacking. Data gathered in this review revealed a rich chemical diversity of hydroxybenzoic acids, cinnamic acids, flavonoids, saponins, and pinitols in A. saligna growing in Egypt, Saudi Arabia, Tunisia, South Africa, and Australia. The variability in phytochemical composition and quantity could be attributed to plant parts, growing locations, extraction solvents, and analysis methods. Identified phytochemicals support observed biological activities such as antioxidant, antimicrobial, anticancer, α-glucosidase inhibition, and anti-inflammation in the extracts. The knowledge of chemical structures, biological activities, and possible mechanisms of action of the bioactive phytochemicals identified in A. saligna were discussed. In addition, the structure–activity relationships of dominant active compounds were examined to explain the bioactivities exerted by A. saligna extracts. The review provides valuable insights towards future research and the development of new therapeutics from this plant. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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12 pages, 974 KiB

Open AccessReview

A Potential Role of Plant/Macrofungi/Algae-Derived Non-Starch Polysaccharide in Colitis Curing: Review of Possible Mechanisms of Action

by Jinxiu Feng, Jingzhang Geng, Jinhui Wu, Huiying Wang, Yanfei Liu, Bin Du, Yuedong Yang and Haitao Xiao

Molecules 2022, 27(19), 6467; https://doi.org/10.3390/molecules27196467 - 01 Oct 2022

Cited by 3 | Viewed by 1911

Abstract

Multiple in vitro and in vivo model investigations have suggested a broad spectrum of potential mechanisms by which plant/macrofungi-derived non-starch polysaccharides may play a role in the treatment of inflammatory bowel disease (IBD). This article reviews the in vivo and in vitro evidence [...] Read more.

Multiple in vitro and in vivo model investigations have suggested a broad spectrum of potential mechanisms by which plant/macrofungi-derived non-starch polysaccharides may play a role in the treatment of inflammatory bowel disease (IBD). This article reviews the in vivo and in vitro evidence of different plant-derived polysaccharides for IBD therapy. Their underlying mechanisms, particularly the molecular mechanisms associated with protective effects in the treatment and prevention of IDB, have been well summarized, including anti-inflammatory, epithelial barrier repair, and the regulation of intestinal flora. Emerging studies have observed the potent role of probiotics in IBD, particularly its ability to modulate gut microbiota, a well-known key factor for IBD. In summary, plant/macrofungi-derived polysaccharides have the potential to be a promising agent for the adjuvant treatment and prevention of IBD and will contribute to the design of well-designed clinical intervention trials that will ultimately improve the therapy of IBD. Full article

(This article belongs to the Special Issue Key Role of Natural Bioactive Compounds in Health and Diseases)

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