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Nutraceuticals and Their Medicinal Importance

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 August 2018) | Viewed by 106209

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Guest Editor
Department of Odontostomatologic and Specialized Clinical Sciences, Sez-Biochimica, Faculty of Medicine, Università Politecnica delle Marche, Via Ranieri 65, 60100 Ancona, Italy
Interests: dietary bioactive compounds; nutrition; disease prevention; mitochondrial impairment; oxidative stress; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The term “nutraceuticals” was introduced by Stephen DeFelice, founder and chairman of the Foundation for Innovation in Medicine, in 1989. A nutraceutical is defined as a “food, or parts of a food, that provide medical or health benefits, including the prevention and treatment of disease”. This definition includes medicinal products made from natural ingredients. Several classes of nutraceuticals have been proposed to have potential benefits in the treatment of many human pathologies, such as cardiovascular diseases, cancer, diabetes and metabolic syndrome, osteoporosis and arthritis, with consequences on quality of life and longevity. Recently, nutraceuticals have been included in conventional therapies, allowing to reduce their dosages and adverse effects. At the same time, consumers have become aware all around the world that nutraceuticals may exert specific roles at different times throughout life and may help to maintain a good health and prevent diseases. In fact, the global annual increase of nutraceutical market is of about 15%.The main aims of the Special Issue on "Nutraceuticals and Their Medicinal Importance" is to be an open forum where researchers may share their investigations and findings in this promising field and, thanks to the open access platform, increase their visibility and the chances to interact with industries and the production systems. Contributions to this issue, both in the form of original research or review articles, may cover all aspects of nutraceuticals; studies with multidisciplinary input, offering new methodologies or insights, are particularly welcome.

Dr. Francesca Giampieri
Guest Editor

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Keywords

  • nutraceuticals
  • bioactive compounds
  • functional foods
  • medicinal products
  • health
  • disease prevention
  • quality control
  • food processing techniques
  • safety and efficacy
  • bioavailability
  • dietary supplements
  • commercialization of nutraceuticals and functional foods
  • economic and industry opportunities
  • labelling and health claims

Published Papers (18 papers)

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Research

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15 pages, 2003 KiB  
Article
The Impact of O-Glycosylation on Cyanidin Interaction with POPC Membranes: Structure-Activity Relationship
by Sylwia Cyboran-Mikołajczyk, Piotr Jurkiewicz, Martin Hof and Halina Kleszczyńska
Molecules 2018, 23(11), 2771; https://doi.org/10.3390/molecules23112771 - 25 Oct 2018
Cited by 13 | Viewed by 2965
Abstract
Cyanidin and its O-glycosides have many important physiological functions in plants and beneficial effects on human health. Their biological activity is not entirely clear and depends on the structure of the molecule, in particular, on the number and type of sugar substituents. Therefore, [...] Read more.
Cyanidin and its O-glycosides have many important physiological functions in plants and beneficial effects on human health. Their biological activity is not entirely clear and depends on the structure of the molecule, in particular, on the number and type of sugar substituents. Therefore, in this study the detailed structure-activity relationship (SARs) of the anthocyanins/anthocyanidins in relation to their interactions with lipid bilayer was determined. On the basis of their antioxidant activity and the changes induced by them in size and Zeta potential of lipid vesicles, and mobility and order of lipid acyl chains, the impact of the number and type of sugar substituents on the biological activity of the compounds was evaluated. The obtained results have shown, that 3-O-glycosylation changes the interaction of cyanidin with lipid bilayer entirely. The 3-O-glycosides containing a monosaccharide induces greater changes in physical properties of the lipid membrane than those containing disaccharides. The presence of additional sugar significantly reduces glycoside interaction with model lipid membrane. Furthermore, O-glycosylation alters the ability of cyanidin to scavenge free radicals. This alteration depends on the type of free radicals and the sensitivity of the method used for their determination. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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17 pages, 1596 KiB  
Article
Pharmacokinetic, Antiproliferative and Apoptotic Effects of Phenolic Acids in Human Colon Adenocarcinoma Cells Using In Vitro and In Silico Approaches
by Lana De Souza Rosa, Nathállia Araújo Jordão, Nathália Da Costa Pereira Soares, Joelma Freire DeMesquita, Mariana Monteiro and Anderson Junger Teodoro
Molecules 2018, 23(10), 2569; https://doi.org/10.3390/molecules23102569 - 8 Oct 2018
Cited by 44 | Viewed by 4230
Abstract
Colon cancer is the second most common cause of cancer deaths in the USA and Europe. Despite aggressive therapies, many tumors are resistant to current treatment protocols and epidemiological data suggest that diet is a major factor in the etiology of colon cancer. [...] Read more.
Colon cancer is the second most common cause of cancer deaths in the USA and Europe. Despite aggressive therapies, many tumors are resistant to current treatment protocols and epidemiological data suggest that diet is a major factor in the etiology of colon cancer. This study aimed to evaluate the antioxidant activity and the influence of 3,4-dihydroxyphenylacetic (3,4-DHPAA), p-coumaric (p-CoA), vanillic (VA) and ferulic (FA) acids on cell viability, cell cycle progression, and rate of apoptosis in human colon adenocarcinoma cells (HT-29). The results showed that all compounds tested reduce cell viability in human colon cancer cells. 3,4-DHPAA promoted the highest effect antiproliferative with an increase in the percentage of cells in G0/G1 phase, accompanied by a reduction of cells in G2/M phase. Cell cycle analysis of VA and FA showed a decrease in the proportion of cells in G0/G1 phase (10.0 µM and 100.0 µM). p-CoA and FA acids increased the percentage of apoptotic cells and non-apoptotic cells. 3,4-DHPAA seems to be the substance with the greatest potential for in vivo studies, opening thus a series of perspectives on the use of these compounds in the prevention and treatment of colon cancer. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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22 pages, 2230 KiB  
Article
Valorization of Olive Pomace-Based Nutraceuticals as Antioxidants in Chemical, Food, and Biological Models
by Dubravka Vitali Čepo, Kristina Radić, Sanja Jurmanović, Mario Jug, Marija Grdić Rajković, Sandra Pedisić, Tihomir Moslavac and Petra Albahari
Molecules 2018, 23(8), 2070; https://doi.org/10.3390/molecules23082070 - 18 Aug 2018
Cited by 34 | Viewed by 6317
Abstract
Waste remaining after the production of olive oil (olive pomace) is known to contain significant amounts of phenolic compounds that exert different types of biological activities, primarily acting as antioxidants. In this work, a sustainable approach that combines ultrasound-assisted extraction with food-grade solvents [...] Read more.
Waste remaining after the production of olive oil (olive pomace) is known to contain significant amounts of phenolic compounds that exert different types of biological activities, primarily acting as antioxidants. In this work, a sustainable approach that combines ultrasound-assisted extraction with food-grade solvents and encapsulation with different types of cyclodextrins was used to prepare olive pomace-based polyphenol rich extracts that were tested as antioxidants in various chemical, food, and biological model systems. Encapsulation with cyclodextrins had a significant positive impact on the chemical composition of obtained extracts and it positively affected their antioxidant activity. Observed effects can be explained by an increased content of polyphenols in the formulations, specific physical properties of encapsulated compounds improving their antioxidant activity in complex food/physiological environment, and enhanced interaction with natural substrates. Depending on the applied model, the tested samples showed significant antioxidant protection in the concentration range 0.1–3%. Among the investigated cyclodextrins, hydroxypropyl-β-cyclodextrin and randomly methylated-β-cyclodextrin encapsulated extracts showed particularly good antioxidant activity and were especially potent in oil-in-water emulsion systems (1242 mg/g and 1422 mg/g of Trolox equivalents, respectively), showing significantly higher antioxidant activity than Trolox (reference antioxidant). In other models, they provided antioxidant protection comparable to commonly used synthetic antioxidants at concentration levels of 2–3%. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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12 pages, 3333 KiB  
Article
In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones
by Seungeun Lee, Kumju Youn, GyuTae Lim, Jinhyuk Lee and Mira Jun
Molecules 2018, 23(7), 1509; https://doi.org/10.3390/molecules23071509 - 22 Jun 2018
Cited by 41 | Viewed by 5430
Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, distinctively characterized by senile plaques, neurofibrillary tangles, and synaptic loss, finally resulting in neuronal death. β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and cholinesterases have been identified as therapeutic targets for AD, [...] Read more.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, distinctively characterized by senile plaques, neurofibrillary tangles, and synaptic loss, finally resulting in neuronal death. β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and cholinesterases have been identified as therapeutic targets for AD, and the discovery of their inhibitors is of critical importance for developing preventive strategies for AD. To discover natural multi-target compounds possessing BACE1, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory properties, major citrus flavanones including hesperetin, naringenin, and hesperidin were evaluated. In vitro anti-AD activities were performed via BACE1 and cholinesterases inhibition assays, as well as enzyme kinetic predictions. For the design of potential inhibitors of AD-related enzymes, molecular docking analysis was performed. Based on the biological evaluation, hesperidin demonstrated the best inhibitory properties toward BACE1, AChE, and BChE, with IC50 values of 10.02 ± 1.12, 22.80 ± 2.78, and 48.09 ± 0.74 µM, respectively. Kinetic studies revealed that all tested compounds were found to be noncompetitive inhibitors against BACE1 and cholineseterases. In addition, molecular docking studies of these compounds demonstrated negative binding energies for BACE1, AChE, and BChE, indicating high affinity and tight binding capacity for the target enzymes. The present study suggested that the selected citrus flavanones could act together as multiple inhibitors of BACE1, AChE, and BChE, indicating preventive and therapeutic potential against AD. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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20 pages, 3586 KiB  
Article
Application of a JA-Ile Biosynthesis Inhibitor to Methyl Jasmonate-Treated Strawberry Fruit Induces Upregulation of Specific MBW Complex-Related Genes and Accumulation of Proanthocyanidins
by Laura D. Delgado, Paz E. Zúñiga, Nicolás E. Figueroa, Edgar Pastene, Hugo F. Escobar-Sepúlveda, Pablo M. Figueroa, Adrián Garrido-Bigotes and Carlos R. Figueroa
Molecules 2018, 23(6), 1433; https://doi.org/10.3390/molecules23061433 - 13 Jun 2018
Cited by 33 | Viewed by 5852
Abstract
Fleshy fruits are an important source of anthocyanins and proanthocyanidins (PAs), which protect plants against stress, and their consumption provides beneficial effects for human health. In strawberry fruit, the application of exogenous methyl jasmonate (MeJA) upregulates anthocyanin accumulation, although the relationship between the [...] Read more.
Fleshy fruits are an important source of anthocyanins and proanthocyanidins (PAs), which protect plants against stress, and their consumption provides beneficial effects for human health. In strawberry fruit, the application of exogenous methyl jasmonate (MeJA) upregulates anthocyanin accumulation, although the relationship between the jasmonate pathway and anthocyanin and PA biosynthesis in fruits remains to be understood. Anthocyanin and PA accumulation is mainly regulated at the transcriptional level through R2R3-MYB and bHLH transcription factors in different plant species and organs. Here, the effect of jarin-1, a specific inhibitor of bioactive JA (jasmonoyl-isoleucine, JA-Ile) biosynthesis, on anthocyanin and PA accumulation was evaluated during strawberry (Fragaria × ananassa) fruit development using an in vitro ripening system for 48 h. Also, we observed the effects of MeJA and the application of jarin-1 to MeJA-treated fruits (MeJA + jarin-1 treatment). We assessed changes of expression levels for the JA-Ile and MeJA biosynthetic (FaJAR1.2 and FaJMT), JA signaling-related (FaMYC2 and FaJAZ1), MYB-bHLH-WD40 (MBW) complex-related (FabHLH3/33, FaMYB9/10/11, and repressor FaMYB1), and anthocyanin and PA biosynthetic (FaANS, FaUFGT, FaANR, and FaLAR) genes. In addition, the promoter region of MBW complex-related MYB genes was isolated and sequenced. We found a higher redness of strawberry fruit skin and anthocyanin content in MeJA-treated fruits with respect to jarin-1-treated ones concomitant with an upregulation of FaANS and FaUFGT genes. Inversely, the PA content was higher in jarin-1- and MeJA + jarin-1-treated than in MeJA-treated fruits. MeJA + jarin-1 treatment resulted in an upregulation of FaANR and associated transcription factors such as FabHLH33 and FaMYB9/11 along with FaJMT and FaJAR1.2. Finally, we found JA-responsive elements in the promoter regions of FaMYB1/9/10/11 genes. It is proposed that PA biosynthesis-related genes can be upregulated by the application of jarin-1 to MeJA-treated fruit, thus increasing PA accumulation in strawberry. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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11 pages, 1612 KiB  
Article
Enhanced Antioxidant Activity of Bioactives in Colored Grains by Nano-Carriers in Human Lens Epithelial Cells
by Yoon-Mi Lee, Young Yoon, Haelim Yoon, Sooji Song, Hyun-Min Park, Yu Young Lee, Hyunho Shin, Sung Won Hwang and Kyung-Jin Yeum
Molecules 2018, 23(6), 1327; https://doi.org/10.3390/molecules23061327 - 31 May 2018
Cited by 7 | Viewed by 4267
Abstract
The use of phytochemicals for preventing chronic diseases associated with oxidative stress such as cataracts is hindered by their low bioavailability. The effects of nano-carriers on the antioxidant activities of extracts of black rice with giant embryo (BRGEx) and soybeans (SBx) have been [...] Read more.
The use of phytochemicals for preventing chronic diseases associated with oxidative stress such as cataracts is hindered by their low bioavailability. The effects of nano-carriers on the antioxidant activities of extracts of black rice with giant embryo (BRGEx) and soybeans (SBx) have been determined in human lens epithelial B3 cells. Scanning (SEM) and transmission electron microscopy (TEM) demonstrated that rGO (reduced graphene oxide) has a flat surface unlike GO (graphene oxide), which has a distinctive wrinkled structure with defects. UPLC analysis revealed 41.9 μg/100 g of γ-oryzanols in water extract of BRGE, and 111.8 μg /100 g of lutein, 757.7 μg/100 g of γ-tocotrienol, 4071.4 μg/100 g of γ-tocopherol in 40% ethanol extract of soybeans, respectively. Even though a low concentration of BRGEx alone did not show any antioxidant activity in B3 cells, co-treatment of BRGEx with rGO together substantially reduced hydrogen peroxide and methylglyoxal-induced DNA damage, as determined by phosphorylated γH2AX. In addition, SBx with rGO also attenuated DNA damage. Furthermore, intracellular reactive oxygen species were significantly decreased by combining extracts of these colored grains with rGO. These results suggest a potential application of nanocarriers for enhancing the bioavailability of phytochemicals. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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13 pages, 3591 KiB  
Article
In Vitro Estrogenic and Breast Cancer Inhibitory Activities of Chemical Constituents Isolated from Rheum undulatum L.
by Dahae Lee, SeonJu Park, Sungyoul Choi, Seung Hyun Kim and Ki Sung Kang
Molecules 2018, 23(5), 1215; https://doi.org/10.3390/molecules23051215 - 18 May 2018
Cited by 16 | Viewed by 4778
Abstract
We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized [...] Read more.
We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized E-screen assay in estrogen receptor (ER)-positive MCF-7 cells. The mechanism underlying the breast cancer inhibitory activity of the compounds was studied using human ER-negative MDA-MB-231 and ER-positive MCF-7 cells. The activation of apoptosis pathway-related proteins was investigated by western blotting, using extracts of R. undulatum prepared in three solvent conditions (EX1, EX2, and EX3). The R. undulatum chemical constituents (compounds 13) showed estrogen-like activity in the concentration range of 10 to 50 μM, by increasing the proliferation of human ER-positive MCF-7 cells. These effects were attenuated by co-treatment with 100 nM fulvestrant, an ER antagonist. Compounds 13 decreased the viability of MCF-7 cells in a concentration-dependent manner. Compounds 1 (aloe emodin) and 2 (rhapontigenin) induced mitochondria-independent apoptosis by activating the caspase-8 pathway, whereas the cytotoxic effect of compound 3 (chrysophanol 1-O-β-d-glucopyranoside) was mediated through the mitochondria-dependent apoptotic pathway. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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14 pages, 2850 KiB  
Article
Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model
by Bo-Jeong Pyun, Hyun Yang, Eunjin Sohn, Song Yi Yu, Dongoh Lee, Dong Ho Jung, Byoung Seob Ko and Hye Won Lee
Molecules 2018, 23(5), 1173; https://doi.org/10.3390/molecules23051173 - 14 May 2018
Cited by 14 | Viewed by 4692
Abstract
Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of [...] Read more.
Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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10 pages, 1589 KiB  
Article
Xanthine Oxidase Inhibitory Activity and Thermostability of Cinnamaldehyde-Chemotype Leaf Oil of Cinnamomum osmophloeum Microencapsulated with β-Cyclodextrin
by Chi-Ya Huang, Ting-Feng Yeh, Fu-Lan Hsu, Chun-Ya Lin, Shang-Tzen Chang and Hui-Ting Chang
Molecules 2018, 23(5), 1107; https://doi.org/10.3390/molecules23051107 - 7 May 2018
Cited by 18 | Viewed by 4749
Abstract
The xanthine oxidase inhibitory activity and thermostability of Cinnamomum osmophloeum leaf oil microencapsulated with β-cyclodextrin were evaluated in this study. The yield of leaf oil microcapsules was 86.3% using the optimal reaction conditions at the leaf oil to β-cyclodextrin ratio of 15:85 and [...] Read more.
The xanthine oxidase inhibitory activity and thermostability of Cinnamomum osmophloeum leaf oil microencapsulated with β-cyclodextrin were evaluated in this study. The yield of leaf oil microcapsules was 86.3% using the optimal reaction conditions at the leaf oil to β-cyclodextrin ratio of 15:85 and ethanol to water ratio ranging from 1:3 to 1:5. Based on the FTIR analysis, the characteristic absorption bands of major constituent, trans-cinnamaldehyde, were confirmed in the spectra of leaf oil microcapsules. According to the dry-heat aging test, β-cyclodextrin was thermostable under the high temperature conditions, and it was beneficial to reduce the emission of C. osmophloeum leaf oil. Leaf oil microcapsules exhibited high xanthine oxidase inhibitory activity, with an IC50 value of 83.3 µg/mL. It is concluded that the lifetime of C. osmophloeum leaf oil can be effectively improved by microencapsulation, and leaf oil microcapsules possess superior xanthine oxidase inhibitory activity. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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16 pages, 3340 KiB  
Article
Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats
by Kyung-Hyun Cho, Dhananjay Yadav, Suk-Jeong Kim and Jae-Ryong Kim
Molecules 2018, 23(5), 1080; https://doi.org/10.3390/molecules23051080 - 3 May 2018
Cited by 16 | Viewed by 5753 | Correction
Abstract
We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, [...] Read more.
We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, SHR group fed normal diet (ND), SHR group fed 20 mg of PCO, SHR group fed 100 mg of PCO, and SHR group fed 200 mg of PCO per kg of body weight. After eight weeks, the SHR control group showed gradual increases up to 22% in systolic blood pressure (SBP) and 17.6% in the diastolic blood pressure (DBP) compared with values at week 0. However, policosanol consumption had a dose-dependent reduction effect on SBP and also reduced DBP up to 16% in a dose-dependent manner. Heart rate (HR) bpm increased by six percent in the SHR control, whereas the 20 mg, 100 mg, and 200 mg of policosanol groups showed a reduction of 36%, 28%, and 34% respectively. Although serum total cholesterol (TC) level of SHR was not affected by policosanol consumption (70–80 mg/dL), serum triglyceride (TG) level significantly decreased in the SHR + 200 mg of PCO group. Serum high-density lipoprotein cholesterol (HDL-C) level was also significantly elevated by policosanol consumption. The % HDL-C/TC ratio was elevated in the policosanol group up to 67–70%, whereas the SHR control group showed a ratio of 58%. Serum cholesteryl ester transfer protein (CETP) activity was reduced by policosanol in a dose-dependent manner. Although the serum glutamate oxaloacetate transaminase (GOT)/ glutamate pyruvate transaminase (GPT) were similar across all groups, policosanol consumption caused reduction of reactive oxygen species (ROS) levels in hepatic tissue. The SHR control group showed a 2.1-fold higher serum C-reactive protein (CRP) level than the WKY group, whereas the CRP level decreased in the SHR + 200 mg of PCO group (up to 45%) than SHR control group. Aldosterone level was reduced in the policosanol group (up to 34%) in a dose-dependent manner compared to the control. In conclusion, eight weeks of policosanol consumption in SHR resulted in remarkable reduction of blood pressure, serum aldosterone, and serum TG levels along with the elevation of HDL-C and improvement of hepatic inflammation. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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18 pages, 12369 KiB  
Article
Carotenoid Lutein Selectively Inhibits Breast Cancer Cell Growth and Potentiates the Effect of Chemotherapeutic Agents through ROS-Mediated Mechanisms
by Xiaoming Gong, Joshua R. Smith, Haley M. Swanson and Lewis P. Rubin
Molecules 2018, 23(4), 905; https://doi.org/10.3390/molecules23040905 - 14 Apr 2018
Cited by 100 | Viewed by 10857
Abstract
Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found [...] Read more.
Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found that among several carotenoids (including β-carotene, lutein, and astaxanthin), lutein significantly inhibits breast cancer cell growth by inducing cell-cycle arrest and caspase-independent cell death, but it has little effect on the growth of primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth inhibition of breast cancer cells is quantitatively similar to that induced by chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms showed that lutein treatment significantly increases the intracellular reactive oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells, but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS generation in the growth inhibitory effect of lutein on TNBC cells. Additionally, we found that the p53 signaling pathway is activated and HSP60 levels are increased by lutein treatment, which may contribute partly to the induction of growth inhibition in TNBC cells. Our findings show that lutein promotes growth inhibition of breast cancer cells through increased cell type-specific ROS generation and alternation of several signaling pathways. Dietary lutein supplementation may be a promising alternative and/or adjunct therapeutic candidate against breast cancer. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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15 pages, 2469 KiB  
Article
A Beneficial Role of Rooibos in Diabetes Mellitus: A Systematic Review and Meta-Analysis
by Moe Sasaki, Nami Nishida and Masako Shimada
Molecules 2018, 23(4), 839; https://doi.org/10.3390/molecules23040839 - 6 Apr 2018
Cited by 29 | Viewed by 7464
Abstract
In a rapid increase in cases of diabetes mellitus worldwide, there has been interested in the use of plant-derived polyphenols as nutraceuticals to prevent the onset and progression of diabetes mellitus and its associated complications. Aspalathus linearis, commonly known as rooibos, is [...] Read more.
In a rapid increase in cases of diabetes mellitus worldwide, there has been interested in the use of plant-derived polyphenols as nutraceuticals to prevent the onset and progression of diabetes mellitus and its associated complications. Aspalathus linearis, commonly known as rooibos, is a rich source of uncommon glycosylated plant polyphenols with various critical health-promoting properties, including the prevention and treatment of diabetes mellitus (DM). This study aimed to examine these effects by meta-analyzing the current evidence in diabetic rodent models. Peer-reviewed studies written in English from two databases, PubMed and Embase, were searched up to 28 February 2018. Studies reporting blood glucose levels in diabetic rodents with and without receiving rooibos extracts or their major phenolic compounds are included. Twelve studies enrolling 88 diabetic rodents treated with rooibos extracts or their polyphenols and 85 diabetic control males reported blood glucose levels. The pooled effect size was −0.89 (95% CI: −1.44 to −0.35) with a substantial heterogeneity (I2 = 67.0%). This effect was likely to be modified by type of rooibos extracts and their polyphenols and treatment period. Blood glucose levels were significantly lower in diabetic rodent models treated with the phenolic compound rich in rooibos extracts, PPAG. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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14 pages, 2527 KiB  
Article
Nutraceutical Potential of Phenolics from ′Brava′ and ′Mansa′ Extra-Virgin Olive Oils on the Inhibition of Enzymes Associated to Neurodegenerative Disorders in Comparison with Those of ′Picual′ and ′Cornicabra′
by María Figueiredo-González, Patricia Reboredo-Rodríguez, Carmen González-Barreiro, Alegría Carrasco-Pancorbo, Jesús Simal-Gándara and Beatriz Cancho-Grande
Molecules 2018, 23(4), 722; https://doi.org/10.3390/molecules23040722 - 21 Mar 2018
Cited by 19 | Viewed by 5070
Abstract
The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from ′Brava′ and [...] Read more.
The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from ′Brava′ and ′Mansa′, varieties recently identified from Galicia (northwestern Spain), were selected for in vitro screening to evaluate their capacity to inhibit key enzymes involved in Alzheimer′s disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (5-LOX)), major depressive disorder (MDD) and Parkinson′s disease (PD) (monoamine oxidases: hMAO-A and hMAO-B respectively). ′Brava′ oil exhibited the best inhibitory activity against all enzymes, when they are compared to ′Mansa′ oil: BuChE (IC50 = 245 ± 5 and 591 ± 23 mg·mL−1), 5-LOX (IC50 = 45 ± 7 and 106 ± 14 mg·mL−1), hMAO-A (IC50 = 30 ± 1 and 72 ± 10 mg·mL−1) and hMAO-B (IC50 = 191 ± 8 and 208 ± 14 mg·mL−1), respectively. The inhibitory capacity of the phenolic extracts could be associated with the content of secoiridoids, lignans and phenolic acids. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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18 pages, 10554 KiB  
Article
Comparison of Antioxidative Effects of Insect Tea and Its Raw Tea (Kuding Tea) Polyphenols in Kunming Mice
by Xin Zhao, Jia-Le Song, Ruokun Yi, Guijie Li, Peng Sun, Kun-Young Park and Huayi Suo
Molecules 2018, 23(1), 204; https://doi.org/10.3390/molecules23010204 - 19 Jan 2018
Cited by 42 | Viewed by 5244
Abstract
Kudingcha is a traditional Chinese tea, and insect tea is a special drink produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity polyphenols extracted by centrifuge [...] Read more.
Kudingcha is a traditional Chinese tea, and insect tea is a special drink produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity polyphenols extracted by centrifuge precipitation. The present study was designed to compare the antioxidative effects of insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) on d-galactose-induced oxidation in Kunming (KM) mice. KM mice were treated with ITP (200 mg/kg) and KTP (200 mg/kg) by gavage, and vitamin C (VC, 200 mg/kg) was also used as a positive control by gavage. After determination in serum, liver and spleen, ITP-treated mice showed higher superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) activities and lower nitric oxide (NO), malonaldehyde (MDA) activities than VC-treated mice, KTP-treated mice and untreated oxidation mice (control group). By H&E section observation, the mice induced by d-galactose-induced oxidation showed more changes than normal mice, and oxidative damage appeared in liver and spleen tissues; ITP, VC and KTP improved oxidative damage of liver and spleen tissues, and the effects of ITP were better than VC and KTP. Using quantitative polymerase chain reaction (qPCR) and western blot experiments, it was observed that ITP could increase the mRNA and protein expression of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), manganese superoxide dismutase (Mn-SOD), cupro/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor erythroid 2 related factor 2 (Nrf2), gamma glutamylcysteine synthetase (γ-GCS), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and reduce inducible nitric oxide synthase (iNOS) expression in liver and spleen tissues compared to the control group. These effects were stronger than for VC and KTP. Both ITP and KTP had good antioxidative effects, and after the transformation of insects, the effects of ITP were better than that of KTP and even better than VC. Thus, ITP can be used as an antioxidant and anti-ageing functional food. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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Review

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19 pages, 1515 KiB  
Review
Use of Nutraceuticals in Angiogenesis-Dependent Disorders
by Lucia Morbidelli, Erika Terzuoli and Sandra Donnini
Molecules 2018, 23(10), 2676; https://doi.org/10.3390/molecules23102676 - 18 Oct 2018
Cited by 20 | Viewed by 4635
Abstract
The term of angiogenesis refers to the growth of new vessels from pre-existing capillaries. The phenomenon is necessary for physiological growth, repair and functioning of our organs. When occurring in a not regulated manner, it concurs to pathological conditions as tumors, eye diseases, [...] Read more.
The term of angiogenesis refers to the growth of new vessels from pre-existing capillaries. The phenomenon is necessary for physiological growth, repair and functioning of our organs. When occurring in a not regulated manner, it concurs to pathological conditions as tumors, eye diseases, chronic degenerative disorders. On the contrary insufficient neovascularization or endothelial disfunction accompanies ischemic and metabolic disorders. In both the cases an inflammatory and oxidative condition exists in supporting angiogenesis deregulation and endothelial dysfunction. The use of nutraceuticals with antioxidant and anti-inflammatory activities can be a therapeutic option to maintain an adequate vascularization and endothelial cell proper functioning or to blunt aberrant angiogenesis. A revision of the updated literature reports on nutraceuticals to guide endothelial cell wellness and to restore physiological tissue vascularization is the objective of this paper. The critical aspects as well as lacking data for human use will be explored from a pharmacological perspective. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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29 pages, 343 KiB  
Review
Nutraceuticals in Periodontal Health: A Systematic Review on the Role of Vitamins in Periodontal Health Maintenance
by Alfonso Varela-López, María D. Navarro-Hortal, Francesca Giampieri, Pedro Bullón, Maurizio Battino and José L. Quiles
Molecules 2018, 23(5), 1226; https://doi.org/10.3390/molecules23051226 - 20 May 2018
Cited by 42 | Viewed by 7913
Abstract
Periodontal disease, a relevant public health problem worldwide, is generally considered a common pathology of elderly people. In this respect, there is agreement about that nutritional status may be a modifying factor in the progression and healing of the periodontal tissues. Vitamins have [...] Read more.
Periodontal disease, a relevant public health problem worldwide, is generally considered a common pathology of elderly people. In this respect, there is agreement about that nutritional status may be a modifying factor in the progression and healing of the periodontal tissues. Vitamins have been recommended as nutraceuticals for prevention and treatment of some pathological conditions, such as cardiovascular diseases, obesity or cancer. Thus, a systematic approach to determining how the different vitamin type could ameliorate periodontal risks or improve periodontal health is necessary to further the understanding of the potential benefits and risks of vitamins supplementation use. For this, a systematic review of English-written literature in PubMed until February 2018, which included both human and animal research on the relationship of each vitamin with periodontal disease, was conducted. Among all the analyzed vitamins those with antioxidant capacity and effects on immune system seem to be useful for prevention or improvement of periodontal disease, as well as those implicated in bone metabolism. In the first case, there are quite information in favor of various vitamins, mainly vitamin C, that is the most studied. In the second case, vitamin D seems to have the most relevant role. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
19 pages, 943 KiB  
Review
Nutraceutical and Ethnopharmacological Properties of Vangueria infausta subsp. infausta
by Alfred Maroyi
Molecules 2018, 23(5), 1089; https://doi.org/10.3390/molecules23051089 - 4 May 2018
Cited by 19 | Viewed by 6450
Abstract
Vangueria infausta subsp. infausta (VI) is a nutraceutical with plant parts valued in several cultures for its medicinal properties. Traditionally, VI is used against gastro-intestinal disorders, malaria, pneumonia, cough, menstrual problems, parasitic worms, chest complaints, snake bites, infertility, fever, candidiasis and abdominal pains. [...] Read more.
Vangueria infausta subsp. infausta (VI) is a nutraceutical with plant parts valued in several cultures for its medicinal properties. Traditionally, VI is used against gastro-intestinal disorders, malaria, pneumonia, cough, menstrual problems, parasitic worms, chest complaints, snake bites, infertility, fever, candidiasis and abdominal pains. This study aims to critically summarize the nutraceutical properties, phytochemistry and pharmacology of VI with a view to provide baseline data required for further investigations on this plant. Relevant information on the nutraceutical and ethnopharmacological properties of VI was collected from established scientific databases such as ScienceDirect, SciFinder, PubMed, Google Scholar, Medline, and SCOPUS. Additionally, books, book chapters and conference papers were also consulted to access other important information. Comparative analysis of the literature revealed that VI is an important neutraceutical plant in east and southern Africa, used as herbal medicine in 69% of the countries where the species is native. Phytochemical studies revealed the presence in VI of fatty acids, flavonoids, iridoid lactones and triterpenoids. Based on in vitro and animal studies, the species exhibited antibacterial, antimycobacterial, antifungal, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial, antifeedant and prostaglandin synthesis inhibitory activities. Pharmacological studies have provided supporting evidence for the therapeutic value of VI, however, detailed toxicological and clinical trials are required to assess efficacy of the species. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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31 pages, 501 KiB  
Review
An Overview of Novel Dietary Supplements and Food Ingredients in Patients with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease
by Priscila Silva Figueiredo, Aline Carla Inada, Melina Ribeiro Fernandes, Daniela Granja Arakaki, Karine De Cássia Freitas, Rita De Cássia Avellaneda Guimarães, Valter Aragão do Nascimento and Priscila Aiko Hiane
Molecules 2018, 23(4), 877; https://doi.org/10.3390/molecules23040877 - 11 Apr 2018
Cited by 30 | Viewed by 8121
Abstract
Metabolic syndrome (MetS) is characterized by interconnected factors related to metabolic disturbances, and is directly related to the occurrence of some diseases such as cardiovascular diseases and type 2 diabetes. MetS is described as one or both of insulin resistance and visceral adiposity, [...] Read more.
Metabolic syndrome (MetS) is characterized by interconnected factors related to metabolic disturbances, and is directly related to the occurrence of some diseases such as cardiovascular diseases and type 2 diabetes. MetS is described as one or both of insulin resistance and visceral adiposity, considered the initial causes of abnormalities that include hyperglycemia, elevated blood pressure, dyslipidemia, elevated inflammatory markers, and prothrombotic state, as well as polycystic ovarian syndrome in women. Other than in MetS, visceral adiposity and the pro-inflammatory state are also key in the development of non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease in modern society. Both MetS and NAFLD are related to diet and lifestyle, and their treatment may be influenced by dietary pattern changes and the use of certain dietary supplements. This study aimed to review the role of food ingredients and supplements in the management of MetS and NAFLD specifically in human clinical trials. Moreover, bioactive compounds and polyunsaturated fatty acids (PUFAs) may be used as strategies for preventing the onset of and treatment of metabolic disorders, such as MetS and NAFLD, improving the inflammatory state and other comorbidities, such as obesity, dyslipidemias, and cardiovascular diseases (CVD). Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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