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Special Issue "Natural Polyphenols and Health"

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

Deadline for manuscript submissions: 31 December 2018

Special Issue Editors

Guest Editor
Prof. Dr. Margarida Castell Escuer

Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Espanya
Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, Spain
Website | E-Mail
Fax: +93 403 59 01
Interests: flavonoids; antioxidants; allergy; inflammation; immunomodulation; methylxanthines; sport
Guest Editor
Dr. Mariona Camps-Bossacoma

Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Espanya
Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), UB, Spain
Website | E-Mail
Interests: allergy; antibody; cocoa; flavonoids; hesperidin; immunoglobulin; immune system; microbiota; nutraceutical; polyphenols; prebiotic; sentitization; theobromine; tolerance

Special Issue Information

Dear Colleagues,

Polyphenols, found in vegetables as secondary metabolites, are abundant micronutrients in our diet. In the last few decades, there has been a growing interest in their potential health benefits. This Special Issue of Molecules entitled “Natural Polyphenols and Health” will focus on the relevant current knowledge of polyphenols in the improvement or prevention of some diseases, as well as in a healthy status, to provide the most recent perspectives of this area. Papers of interest include research of any polyphenol, either as a pure compound or included in a food in in vitro and in vivo studies. Study designs can include clinical and preclinical aspects developed at in any stage of life and any health threats. Observational studies as well as those establishing the preventive effects of polyphenols for human and animal models are also welcome. Health aspects can include nervous, cardiovascular, intestinal, immune systems or any physiological system. It is a pleasure to invite original research as well as review articles that describe or detail the influence of polyphenols on health.

Prof. Dr. Margarida Castell Escuer
Dr. Mariona Camps-Bossacoma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antioxidant
  • Cardiovascular system
  • Flavonoids
  • Immune system
  • Intestinal system
  • Microbiota
  • Nervous system
  • Physiology

Published Papers (10 papers)

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Research

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Open AccessArticle The Flavonoid Kaempferol Ameliorates Streptozotocin-Induced Diabetes by Suppressing Hepatic Glucose Production
Molecules 2018, 23(9), 2338; https://doi.org/10.3390/molecules23092338
Received: 24 July 2018 / Revised: 4 September 2018 / Accepted: 8 September 2018 / Published: 13 September 2018
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Abstract
In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can
[...] Read more.
In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal model of insulin deficiency and further explored the mechanism underlying the anti-diabetic effect of this flavonol. We demonstrate that oral administration of kaempferol (50 mg/kg/day) to streptozotocin-induced diabetic mice significantly improved hyperglycemia and reduced the incidence of overt diabetes from 100% to 77.8%. This outcome was accompanied by a reduction in hepatic glucose production and an increase in glucose oxidation in the muscle of the diabetic mice, whereas body weight, calorie intake, body composition, and plasma insulin and glucagon levels were not altered. Consistently, treatment with kaempferol restored hexokinase activity in the liver and skeletal muscle of diabetic mice while suppressed hepatic pyruvate carboxylase activity and gluconeogenesis. These results suggest that kaempferol may exert antidiabetic action via promoting glucose metabolism in skeletal muscle and inhibiting gluconeogenesis in the liver. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessFeature PaperArticle Identification of Antiglycative Compounds in Japanese Red Water Pepper (Red Leaf Variant of the Persicaria hydropiper Sprout)
Molecules 2018, 23(9), 2319; https://doi.org/10.3390/molecules23092319
Received: 6 August 2018 / Revised: 10 September 2018 / Accepted: 10 September 2018 / Published: 11 September 2018
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Abstract
Glycation, the nonenzymatic reaction between proteins and excess blood sugar, is implicated in multiple disorders and occurs via the formation and accumulation of advanced glycation end products (AGEs). In our previous studies, we demonstrated that the red-leaf variant of the Persicaria hydropiper sprout
[...] Read more.
Glycation, the nonenzymatic reaction between proteins and excess blood sugar, is implicated in multiple disorders and occurs via the formation and accumulation of advanced glycation end products (AGEs). In our previous studies, we demonstrated that the red-leaf variant of the Persicaria hydropiper sprout (Japanese red water pepper, Benitade) is one of the potent plants that inhibit formation of AGEs. In this study, we aimed to identify antiglycative compounds in Benitade. Benitade extracts were prepared with hot water, then fractionated by using high-performance liquid chromatography (HPLC). The antiglycative efficacy of each fraction was evaluated by measuring the formation of fluorescent AGEs (Ex 370 nm/Em 440 nm). Two fractions, which contained peaks at 26.4 min and 31.8 min, showed potent antiglycative efficacy. When we hydrolyzed these peaks, they shifted to 32.5 and 41.4 min, which are the same retention times as cyanidin and quercetin, respectively. Based on thin-layer chromatography, both compounds contained galactose. Finally, ultrahigh-performance liquid chromatography/quadrupole-time of flight mass spectrometry (UHPLC-QqTOF-MS) analyses were performed to determine the structure of those compounds. Overall, we identified two glycosides, cyanidin 3-O-galactoside (idaein) and quercetin 3-O-galactoside (hyperin), as representative antiglycative compounds in Benitade. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle Effect of Storage Conditions on Phenolic Profiles and Antioxidant Activity of Litchi Pericarp
Molecules 2018, 23(9), 2276; https://doi.org/10.3390/molecules23092276
Received: 7 August 2018 / Revised: 29 August 2018 / Accepted: 3 September 2018 / Published: 6 September 2018
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Abstract
Changes of phenolic profiles and antioxidant activity of litchi pericarp during storage at 4 °C for seven days and at room temperature (RT) for 72 h were evaluated in this study. The contents of total phenolic and procyanidin decreased by 20.2% and 24.2%
[...] Read more.
Changes of phenolic profiles and antioxidant activity of litchi pericarp during storage at 4 °C for seven days and at room temperature (RT) for 72 h were evaluated in this study. The contents of total phenolic and procyanidin decreased by 20.2% and 24.2% at 4 °C and by 37.8% and 47.8% at RT, respectively. Interestingly, the corresponding reductions of anthocyanins were 41.3% and 73%, respectively. Four phenolic compounds, including epicatechin, procyanidin A2, procyanidin B2, and quercetin-3-O-rutinoside-7-O-α-l-rhamnosidase were detected in litchi pericarp. Their contents after storage at 4 °C and at RT were decreased by 22.1–49.7% and 27.6–48.7%, respectively. The oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) of litchi pericarp decreased by 17.6% and 58.7% at 4 °C, and by 23.4% and 66.0% at RT, respectively. The results indicated that storage at 4 °C preserved more phenolics and retained higher antioxidant activity in litchi pericarp compared to storage at RT, suggesting that storage at 4 °C should be considered as a more effective method for slowing down the degradation of litchi pericarp phenolics. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle Polyphenols from Acorn Leaves (Quercus liaotungensis) Protect Pancreatic Beta Cells and Their Inhibitory Activity against α-Glucosidase and Protein Tyrosine Phosphatase 1B
Molecules 2018, 23(9), 2167; https://doi.org/10.3390/molecules23092167
Received: 24 July 2018 / Revised: 22 August 2018 / Accepted: 23 August 2018 / Published: 28 August 2018
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Abstract
Acorn leaves, which possess potential pharmacologic effects, are traditionally consumed as food in China. Phytochemical investigations of acorn leaves yielded one new and 25 known polyphenols, and their structures were identified by extensive spectroscopic analysis. Three antidiabetes assays were conducted. Compound 2 considerably
[...] Read more.
Acorn leaves, which possess potential pharmacologic effects, are traditionally consumed as food in China. Phytochemical investigations of acorn leaves yielded one new and 25 known polyphenols, and their structures were identified by extensive spectroscopic analysis. Three antidiabetes assays were conducted. Compound 2 considerably increased the survival of pancreatic beta cells by reducing the production of reactive oxygen species and enhancing the activities of superoxide dismutase, catalase, and glutathione in MIN6 cells damaged by H2O2. The preliminary mechanism by which compound 2 protects pancreatic beta cells was through the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 HO-1 pathway. Most of the tested isolates showed strong inhibitory activity against α-glucosidase and protein tyrosine phosphatase 1B. The IC50 values of most compounds were much lower than those of the positive control. The results suggest that polyphenols from acorn leaves are potential functional food ingredients that can be used as antidiabetic agents. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle Raspberry Polyphenolic Extract Regulates Obesogenic Signals in Hepatocytes
Molecules 2018, 23(9), 2103; https://doi.org/10.3390/molecules23092103
Received: 20 July 2018 / Revised: 8 August 2018 / Accepted: 18 August 2018 / Published: 21 August 2018
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Abstract
The aim of this in vitro study was to examine the effect of raspberry polyphenolic extract on the immune-metabolic molecular mechanisms activated by obesity-related signals in hepatocytes (HB-8965®). Alterations in endosomal/lysosomal activity (neutral red uptake assay, NR), the expression of selected
[...] Read more.
The aim of this in vitro study was to examine the effect of raspberry polyphenolic extract on the immune-metabolic molecular mechanisms activated by obesity-related signals in hepatocytes (HB-8965®). Alterations in endosomal/lysosomal activity (neutral red uptake assay, NR), the expression of selected genes involved with lipid oxidation, and metabolism and inflammation processes in the liver were studied. Hepatocytes were treated with plasma collected from Wistar rats that were fed a high-fat diet (HF), raspberry polyphenolic extract (PP), serine-type protease inhibitors as an agonist of TLR4 (TD) or a combination of PP with HF or TD treatments. The PP added to the experimental treatments modulated hepatic immune-metabolic mechanisms through the upregulation of STAT1, ANGPTL4, and CD44, as well as considerably reducing the NR uptake and downregulation of COX-2 and the multifunctional protein AhR. The kinetic analysis of AhR expression revealed that HF-related molecular mechanisms activated AhR mRNA expression earlier than PP initiated the regulatory effect. In conclusion, PP might be considered a valuable dietary agent that regulates obesity-related signals in hepatocytes. Moreover, taking AhR kinetic behavior into consideration, it can be assumed that PP might modulate the severity of the HF-induced downstream metabolic signaling of AhR. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle Nontargeted Metabolomics for Phenolic and Polyhydroxy Compounds Profile of Pepper (Piper nigrum L.) Products Based on LC-MS/MS Analysis
Molecules 2018, 23(8), 1985; https://doi.org/10.3390/molecules23081985
Received: 16 July 2018 / Revised: 3 August 2018 / Accepted: 7 August 2018 / Published: 9 August 2018
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Abstract
In the present study, nontargeted metabolomics was used to screen the phenolic and polyhydroxy compounds in pepper products. A total of 186 phenolic and polyhydroxy compounds, including anthocyanins, proanthocyanidins, catechin derivatives, flavanones, flavones, flavonols, isoflavones and 3-O-p-coumaroyl quinic acid
[...] Read more.
In the present study, nontargeted metabolomics was used to screen the phenolic and polyhydroxy compounds in pepper products. A total of 186 phenolic and polyhydroxy compounds, including anthocyanins, proanthocyanidins, catechin derivatives, flavanones, flavones, flavonols, isoflavones and 3-O-p-coumaroyl quinic acid O-hexoside, quinic acid (polyhydroxy compounds), etc. For the selected 50 types of phenolic compound, except malvidin 3,5-diglucoside (malvin), l-epicatechin and 4′-hydroxy-5,7-dimethoxyflavanone, other compound contents were present in high contents in freeze-dried pepper berries, and pinocembrin was relatively abundant in two kinds of pepper products. The score plots of principal component analysis indicated that the pepper samples can be classified into four groups on the basis of the type pepper processing. This study provided a comprehensive profile of the phenolic and polyhydroxy compounds of different pepper products and partly clarified the factors responsible for different metabolite profiles in ongoing studies and the changes of phenolic compounds for the browning mechanism of black pepper. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle Antioxidant Activity of Selected Polyphenolics in Yeast Cells: The Case Study of Montenegrin Merlot Wine
Molecules 2018, 23(8), 1971; https://doi.org/10.3390/molecules23081971
Received: 29 June 2018 / Revised: 30 July 2018 / Accepted: 31 July 2018 / Published: 7 August 2018
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Abstract
Screens of antioxidant activity (AA) of various natural products have been a focus of the research community worldwide. This work aimed to differentiate selected samples of Merlot wines originated from Montenegro, with regard to phenolic profile and antioxidant capacity studied by survival rate,
[...] Read more.
Screens of antioxidant activity (AA) of various natural products have been a focus of the research community worldwide. This work aimed to differentiate selected samples of Merlot wines originated from Montenegro, with regard to phenolic profile and antioxidant capacity studied by survival rate, total sulfhydryl groups and activities of glutathione peroxidase (GPx), glutathione reductase and catalase in H2O2–stressed Saccharomyces cerevisiae cells. In this study, DPPH assay was also performed. Higher total phenolic content leads to an enhanced AA under both conditions. The same trend was observed for catechin and gallic acid, the most abundant phenolics in the examined wine samples. Finally, the findings of an Artificial Neural Network (ANN) model were in a good agreement (r2 = 0.978) with the experimental data. All tested samples exhibited a protective effect in H2O2–stressed yeast cells. Pre-treatment with examined wines increased survival in H2O2–stressed cells and shifted antioxidative defense towards GPx–mediated defense. Finally, sensitivity analysis of obtained ANN model highlights the complexity of the impact that variations in the concentrations of specific phenolic components have on the antioxidant defense system. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle Alpha-Mangostin-Rich Extracts from Mangosteen Pericarp: Optimization of Green Extraction Protocol and Evaluation of Biological Activity
Molecules 2018, 23(8), 1852; https://doi.org/10.3390/molecules23081852
Received: 14 June 2018 / Revised: 21 July 2018 / Accepted: 24 July 2018 / Published: 25 July 2018
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Abstract
Since α-mangostin in mangosteen fruits was reported to be the main compound able to provide natural antioxidants, the microwave-assisted extraction process to obtain high-quality α-mangostin from mangosteen pericarp (Garcinia mangostana L.) was optimized using a central composite design and response surface methodology.
[...] Read more.
Since α-mangostin in mangosteen fruits was reported to be the main compound able to provide natural antioxidants, the microwave-assisted extraction process to obtain high-quality α-mangostin from mangosteen pericarp (Garcinia mangostana L.) was optimized using a central composite design and response surface methodology. The parameters examined included extraction time, microwave power, and solvent percentage. The antioxidant and antimicrobial activity of optimized and non-optimized extracts was evaluated. Ethyl acetate as a green solvent exhibited the highest concentration of α-mangostin, followed by dichloromethane, ethanol, and water. The highest α-mangostin concentration in mangosteen pericarp of 121.01 mg/g dry matter (DM) was predicted at 3.16 min, 189.20 W, and 72.40% (v/v). The verification of experimental results under these optimized conditions showed that the α-mangostin value for the mangosteen pericarp was 120.68 mg/g DM. The predicted models were successfully developed to extract α-mangostin from the mangosteen pericarp. No significant differences were observed between the predicted and the experimental α-mangostin values, indicating that the developed models are accurate. The analysis of the extracts for secondary metabolites showed that the total phenolic content (TPC) and total flavonoid content (TFC) increased significantly in the optimized extracts (OE) compared to the non-optimized extracts (NOE). Additionally, trans-ferulic acid and catechin were abundant among the compounds identified. In addition, the optimized extract of mangosteen pericarp with its higher α-mangostin and secondary metabolite concentrations exhibited higher antioxidant activities with half maximal inhibitory concentration (IC50) values of 20.64 µg/mL compared to those of the NOE (28.50 µg/mL). The OE exhibited the highest antibacterial activity, particularly against Gram-positive bacteria. In this study, the microwave-assisted extraction process of α-mangostin from mangosteen pericarp was successfully optimized, indicating the accuracy of the models developed, which will be usable in a larger-scale extraction process. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Open AccessArticle The Use of Juçara (Euterpe edulis Mart.) Supplementation for Suppression of NF-κB Pathway in the Hypothalamus after High-Fat Diet in Wistar Rats
Molecules 2018, 23(7), 1814; https://doi.org/10.3390/molecules23071814
Received: 12 June 2018 / Revised: 17 July 2018 / Accepted: 18 July 2018 / Published: 21 July 2018
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Abstract
Obesity is associated with modern diets that are rich in saturated fatty acids. These dietary patterns are linked to low-grade proinflammatory mechanisms, such as the toll-like receptor 4/nuclear factor kappa-B (NF-κB) pathway rapidly activated through high-fat diets. Juçara is a berry rich in
[...] Read more.
Obesity is associated with modern diets that are rich in saturated fatty acids. These dietary patterns are linked to low-grade proinflammatory mechanisms, such as the toll-like receptor 4/nuclear factor kappa-B (NF-κB) pathway rapidly activated through high-fat diets. Juçara is a berry rich in anthocyanins and unsaturated fatty acids, which prevents obesity and associated comorbidities. We evaluated the effect of different doses of freeze-dried juçara pulp on NF-κB pathway after the consumption of short-term high-fat diet. Male Wistar rats with ad libitum access to food and water were divided into four groups: Control diet (C), high-fat diet (HFC), high-fat diet with 0.25% juçara (HFJ 0.25%), and high-fat diet with 0.5% juçara (HFJ 0.5%). Energy intake and body weight gain were increased in HFC and HFJ 0.5% groups compared to C group. The hypothalamus weight reduced in the HFC group compared to C and HFJ 0.25% groups. Cytokines, MYD88, TRAF6, and pNF-κBp50 levels in the hypothalamus, serum triacylglycerol, LDL-cholesterol (LDL-C), and free fatty acid levels were improved in the HFJ 0.25% group. In summary, the HFJ 0.25% group had better protective effects than those in the HFJ 0.5%. Therefore, 0.25% juçara can be used to protect against central inflammation through the high-fat diet-induced NF-κB pathway. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Review

Jump to: Research

Open AccessReview Dietary Polyphenols and Periodontitis—A Mini-Review of Literature
Molecules 2018, 23(7), 1786; https://doi.org/10.3390/molecules23071786
Received: 10 June 2018 / Revised: 14 July 2018 / Accepted: 18 July 2018 / Published: 20 July 2018
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Abstract
Periodontitis, which is a chronic infection and disease of the periodontium, is a significant global health burden and is linked to other chronic health conditions such as diabetes and cardiovascular diseases. Dietary polyphenols present in a wide variety of plant-based foods, herbs, and
[...] Read more.
Periodontitis, which is a chronic infection and disease of the periodontium, is a significant global health burden and is linked to other chronic health conditions such as diabetes and cardiovascular diseases. Dietary polyphenols present in a wide variety of plant-based foods, herbs, and botanicals have been shown to exert antimicrobial, anti-inflammatory, and reduced osteoclast and alveolar bone loss activities in animal models of periodontitis. Polyphenol-containing beverages and foods especially green tea and its active catechin epigallocatechin-3-gallate, cranberries, pomegranates, and fruit and vegetable extracts have reported bacteriostatic/bactericidal activity against microbial species such as P. gingivalis and shown total bacterial burden in clinical studies. These polyphenols also exhibit anti-inflammatory and antioxidant effects, which have the potential to impact various biological mechanisms for reducing the initiation and progression of periodontitis. The main objective of this mini-review is to focus on the mechanisms of action of dietary polyphenols in improving the pathophysiology underlying chronic inflammatory diseases like periodontitis based on pre-clinical and clinical models. Full article
(This article belongs to the Special Issue Natural Polyphenols and Health)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Author: Arpita Basu1, Emily Masek1, Jeffrey Ebersole2
Affiliation:
1 Kinesiology and Nutrition Sciences, University of Nevada at Las Vegas, Las Vegas, NV, USA
2 School of Dental Medicine, University of Nevada at Las Vegas, Las Vegas, NV, USA
Tentative title: Dietary polyphenols and periodontitis- a mini-review of literature
Tentative abstract: Periodontitis, a chronic disease of the periodontium has been emerging as a significant global health burden, and linked to other conditions such as diabetes and cardiovascular diseases. Dietary polyphenols present in a wide variety of plant-based foods, herbs and botanicals have been shown to exert antimicrobial, anti-inflammatory and reduced osteoclast and alveolar bone loss activities in animal models of periodontitis. Polyphenol-containing beverages and foods, especially green tea and its active catechin epigallocatechin-3-gallate, cranberries, pomegranates and fruit and vegetable extracts have been reported to exert bactericidal activity against species such as P. gingivalis and general colony forming units in clinical studies. These polyphenols also exhibit anti-inflammatory and antioxidant effects, thus representing various mechanisms of reducing progression of periodontitis. The main objective of this mini-review is to focus on the mechanisms of action of dietary polyphenols in improving the pathophysiology underlying periodontitis in pre-clinical and clinical models.

Author: Minhui Li
Tentative title: The Polyphenols from Salvia Species and their Pharmacological Activities
Tentative abstract: Nowadays, the polyphenols from famous Chinese tradiational medicine Danshen (Salvia miltiorrhiza Bunge) has been used as a functional food.
Polyphenols such as phenolic acids were found in Salvia species. In Salvia species, phenolic acids are chiefly caffeoyl depsidic glycosides. According to the number of caffeic acid units, phenolic acids are divided into unimers, dimers, trimers, tetramer , and other oligomers. Among them the most abundant forms are trimers and tetramers, such as lithospermic acid, salvianolic acid A, salvianolic acid B.
Phenolic acids are used to treat various diseases, particular the cardiovascular and immune system diseases. It can also be used to treat the ant-ibacterial, anti-diabetic, and anti-viral activities.
The review will intend to summarize the polyphenols from Salvia species and their pharmacological activities to make better use of the Salvia species.

Author: Dongmin Liu
Affiliation: Department of Human Nutrition Faculty of Health Sciences ILSB, Mail Code 0913
Corporate Research Center 1981 Kraft Drive, Room 1030 Virginia Tech Blacksburg, VA
Tentative title: Small molecule kaempferol protects against streptozotocin-induced diabetes through suppressing hepatic glucose production
Tentative abstract: In both insulin-deficient type 1 diabetes and type 2 diabetes, the increase in the activity of the key enzymes that control gluconeogenesis and glycogenolysis in the liver causes an increase in the rate of hepatic glucose production, which is the main contributor to the development of hyperglycemia, in particular, fasting hyperglycemia. In the present study, we investigated whether kaempferol, a naturally occurring flavonol present in some medicinal herbs and certain types of foods, can be used to ameliorate diabetes in an insulin-deficient mouse model and further explored the mechanism underlying the anti-diabetic action of this compound. We show that oral administration of kaempferol (50 mg/kg) to streptozotocin-induced diabetic mice significantly ameliorated hyperglycemia and glucose intolerance. After 12 wks of treatment, the incidence of overt diabetes was decreased from 100% to 77.8%. This effect was associated with reduced hepatic glucose production and increased glucose oxidation in the muscle of diabetic mice, whereas body weight (BW), food intake, body composition, or plasma insulin and glucagon levels were not affected. On the molecular level, kaempferol treatment restored hexokinase activity in the liver and skeletal muscle while reduced glycogenolysis and gluconeogenesis via inhibiting pyruvate carboxylase in the liver. These findings suggest that kaempferol holds a great potential to ameliorate diabetes by improving glucose metabolism in skeletal muscle and suppressing hepatic gluconeogenesis.

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