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Absorption​ of free radicals in the body cannot be done by antioxidant compounds originating from the human body, so exogenous antioxidants are required to help in their natural antioxidant action. Oxidative stress can be caused by an imbalance of free radical inhibitors and the accumulation of free radicals that enter cellular structures. Synthetic antioxidants found in external antioxidants are not the primary choice because they are harmful and carcinogenic. Therefore, using natural ingredients provides a necessary alternative to constructing novel natural antioxidants. Recent studies have highlighted critical analysis and evaluation that flavonoids are a unique class of secondary metabolites found in plants and used in communities as traditional therapeutics with proven bioactivity. This could support new discoveries based on various herbal medicines and in addition, the functional effectiveness of flavonoids as antioxidants against free radicals. In this review, there are several strengths in the discussion. First, the study takes a comprehensive approach by covering various aspects, including the properties and sources of free radicals, oxidative stress in relation to different diseases, antioxidant defense mechanisms, and the specific antioxidant mechanisms of flavonoids. Second, the focus on natural antioxidants, especially flavonoids, and also discussion about clinical applications and human studies, limitations, global perspectives, and future research directions of flavonoids compounds become references in the selection of natural medicines. But, several constraints should be considered when interpreting the findings of this review. First, the discussion about the mechanism of antioxidant compounds is only discussed in general and only takes one example of a compound (flavonoid) that has the potential as an antioxidant. Second, the lack of findings regarding the relationship between several diseases discussed with free radicals. Third, a limited number of studies investigated regarding clinical applications and human studies of some of the diseases discussed. [ABSTRACT FROM AUTHOR]

Despite the dramatic advances in our understanding of the etiology of colorectal cancer (CRC) in recent decades, effective therapeutic strategies are still urgently needed. Oncogenic mutations in the Wnt/β‐Catenin pathway are hallmarks of CRC. Moreover, long non‐coding RNAs (lncRNAs) as molecular managers are involved in the initiation, progression, and metastasis of CRC. Therefore, it is important to further explore the interaction between lncRNAs and Wnt/β‐Catenin signaling pathway for targeted therapy of CRC. Natural phytochemicals have not toxicity and can target carcinogenesis‐related pathways. Growing evidences suggest that flavonoids are inversely associated with CRC risk. These bioactive compounds could target carcinogenesis pathways of CRC and reduced the side effects of anti‐cancer drugs. The review systematically summarized the progress of flavonoids targeting lncRNA/Wnt axis in the investigations of CRC, which will provide a promising therapeutic approach for CRC and develop nutrition‐oriented preventive strategies for CRC based on epigenetic mechanisms. In the field, more epidemiological and clinical trials are required in the future to verify feasibility of targeting lncRNA/Wnt axis by flavonoids in the therapy and prevention of CRC. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) pandemic has been triggered by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐2). Although recent studies demonstrate that SARS‐CoV‐2 possibly does not directly infect endothelial cells (EC), the endothelium may be affected as a secondary response due to the damage of neighboring cells, circulating pro‐inflammatory cytokines, and/or other mechanisms. Long‐term COVID‐19 symptoms specifically nonrespiratory symptoms are due to the persistence of endothelial dysfunction (ED). Based on the literature, anthocyanins a major subgroup of flavonoid polyphenols found in berries, have been well researched for their vascular protective properties as well as the prevention of cardiovascular disease (CVD)‐related deaths. Elderberries have been previously used as a natural remedy for treating influenza, cold, and consequently cardiovascular health due to a high content of cyanidin‐3‐glucoside (C3G) a major anthocyanin found in the human diet. The literature reported many studies demonstrating that EE has both antiviral and vascular protective properties that should be further investigated as a nutritional component used against the (in)direct effect of SARS‐CoV‐2 in vascular function. Practical applications: While previous work among the literature looks promising and builds a suggestion for investigating elderberry extract (EE) against COVID‐19, further in vitro and in vivo research is required to fully evaluate EE mechanisms of action and its use as a supplement to aid current therapies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Glucagon-like peptide 1 (GLP-1) is a hormone derived from preproglucagon. It is secreted by enteroendocrine cells in response to feeding and, in turn, acts as a critical regulator of insulin release. Modulating GLP-1 secretion holds promise as a strategy for controlling blood glucose levels.Experimental Approach: To dissect GLP-1 regulation and discover specific secretagogues, we engineered a reporter cell line introducing a luciferase within the proglucagon sequence in GLUTag cells. The assay was validated using western blotting and ELISA. A focused natural compounds library was screened. We measured luminescence, glucose uptake and ATP to investigate the mechanism by which newly found secretagogues potentiate GLP-1 secretion.Key Results: The newly created reporter cell line is ideal for the rapid, sensitive and quantitative assessment of GLP-1 secretion. The small molecule screen identified non-toxic GLP-1 modulators. Quercetin is the most potent newly found GLP-1 secretagogue, while other flavonoids also potentiate GLP-1 secretion. Quercetin requires glucose and extracellular calcium to act as GLP-1 secretagogue. Our results support a mechanism whereby flavonoids cause GLUTag cells to utilize glucose more efficiently, leading to elevated ATP levels, followed by KATP channel blockade and GLP-1 exocytosis.Conclusion and Implications: Our methodology enabled finding of new GLP-1 secretagogues. Quercetin is a potent, naturally occurring GLP-1 secretagogue. Mechanistic studies of newly found secretagogues are possible in newly created reporter cell line. Further validation in more physiological systems, such as primary L-cells or whole organisms, is needed. GLP-1 secretagogues might serve as leads for developing alternative glucose-lowering therapies. [ABSTRACT FROM AUTHOR]

To construct food ingredients with improved bioactivities and physicochemical properties, two sericin hydrolysate–flavonoid conjugates, bearing quercetin and rutin covalently bound to sericin, were prepared under alkaline conditions. UV spectroscopy and SDS‐PAGE confirmed that sericin hydrolysate and oxidized flavonoids formed conjugates, which were primarily the result of covalent interactions. Changes and differences in molecular weight distribution, secondary and tertiary structures, surface hydrophobicity, and surface morphology were observed. Anti‐inflammatory activities were evaluated by basing on inhibitory activity against nitric oxide (NO) production and 15‐lipoxygenase (15‐LOX). The conjugates showed significantly improved (p <.05) anti‐inflammatory and emulsifying properties than unmodified sericin hydrolysate. Meanwhile, the covalent interaction had a positive effect on the antioxidant activity of sericin hydrolysate. Practical applications: We had prepared flavonoid–sericin hydrolysate conjugates and evaluated the effect of covalent binding of flavonoids on the physicochemical, anti‐inflammatory, antioxidant, and emulsifying properties of sericin hydrolysate, which is beneficial to broaden the range of applications of sericin and flavonoids in the food, cosmetics, and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

This study examined the secondary metabolite content and the antioxidant activities of hydromethanolic P. lentiscus L. leaves extracts at different altitudes. The results indicated that the contents of polyphenols and flavonoids were significantly (p ≤ 0.05) high in the low altitude, unlike the Chl (chlorophyll), tannins, and ascorbic acid, which were reported to have higher content in the high altitude. These results showed that the P. lentiscus L. is more adaptable to higher elevations than low elevation, where the plant was probably stressed. On the other hand, the analyses of correlation between the antioxidant activity and phytochemical content affirmed that the antiradical activity (DPPH) correlated with the content of polyphenols; however, the total antioxidant activity is correlated with the flavonoid content. These results revealed the importance of P. lentiscus L. leaves as a natural antioxidant and gave an idea of the altitude effect on the biochemical parameters of leaves. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine if catechin‐rich green tea abrogates the negative effects of 7‐days of physical inactivity and excessive calorie‐intake on insulin homeostasis and peripheral vascular function. Methods: Using a randomized, double‐blind, crossover design, twelve healthy men (29 ± 6 yrs) underwent 7‐days unhealthy lifestyle (UL), including physical inactivity (−50% steps/day) and overfeeding (+50% kcal/day). This was combined with green tea consumption (UL‐tea; 3 doses/day) or placebo (UL‐placebo). Before and after each intervention, we examined postprandial blood glucose and insulin (3‐h after a 1,202 kcal meal) and upper and lower limb vascular function (flow‐mediated dilation (FMD%)) and carotid artery reactivity (CAR%). Results: UL‐placebo increased postprandial glucose and insulin, while UL‐tea decreased postprandial glucose and insulin (Time*Intervention interaction effects: both p < 0.05). UL‐placebo decreased CAR% and femoral FMD%, while UL‐tea prevented these effects (Time*Intervention interaction effects of p < 0.04 and p < 0.001, respectively). There was no main effect of Time or Time*Intervention interaction (both p > 0.05) for brachial FMD%. Conclusion: Seven days of physical inactivity and overfeeding impair insulin homeostasis and vascular function. These effects were mitigated by a daily intake of catechin‐rich green tea. [ABSTRACT FROM AUTHOR]

Several studies investigated the impact of pycnogenol on blood pressure. Nevertheless, the results are inconclusive. The aim of the present systematic review and meta-analysis was to clarify the effect of pycnogenol supplementation on blood pressure. PubMed, Scopus, Web of Science, and Google Scholar were systematically searched until March 2018 to find clinical trials, which examined the effect of pycnogenol supplementation on systolic and diastolic blood pressure in adults. A subgroup analysis was applied to find out potential sources of interstudy heterogeneity. A total of 12 clinical trials (922 participants) were included in the meta-analysis. Pooled analysis suggested that pycnogenol supplementation can reduced systolic blood pressure (SBP) of (-3.22 mmHg; 95% CI [-5.52, -0.92]) and diastolic blood pressure (DBP; -1.91 mmHg; 95% CI [-3.64, -0.18]). Effect of pycnogenol on SBP was more pronounce in subgroup in which pycnogenol was administered along with other treatments. A significant effect of pycnogenol on DBP in studies with >12-week duration, whereas this favorable effect was not observed in subgroup with ≤12-week supplementation. The present systematic review and meta-analysis suggest that pycnogenol had a favorable effect on SBP and DBP. Further, high quality randomized clinical trials are needed to confirm this result. [ABSTRACT FROM AUTHOR]

A diet rich in polyphenolic compounds has recognized health benefits, and as such is routinely monitored as part of dietary intervention studies. A method for the simultaneous determination of 36 phenolic compounds, including phenolic acids and flavonoids, using liquid chromatography and tandem mass spectrometry is described here. The target analytes were quantified based on their specific mass spectral fragments using a selected reaction monitoring approach. A C18 column with embedded aromatic functionality ensured separation of all phenolic compounds studied which included several pairs of isomers. Sample preparation involved the use of β‐glucuronidase to release the phenolic compounds from their conjugated forms. The intra‐day and inter‐day precision and accuracy was less than 7% for all phenolic compounds studied. Recoveries, where plasma was spiked with three different concentrations of the analytes, ranged from 95–115%. The limits of detection and quantification were 0.23–3.89 and 1.15–7.79 nM, respectively. The method was successfully applied to real samples and the range reported for each phenolic compound, with the exception of hydroferulic acid, nordihydroguaiaretic acid, methylgallate, and m‐coumaric acid, was at least an order of magnitude higher than the limit of quantification for the method. [ABSTRACT FROM AUTHOR]

Elm fruits were once an important food source in the years of famine. Research on the functional compounds in elm fruits was almost unavailable. In this study, we established an efficient high‐performance liquid chromatography method for the simultaneous separation of eight chlorogenic acids and 28 flavonoids in elm fruits for the first time. Total flavonoid contents ranged from 286 mg/100 g (Ulmus laciniata) to 1228 mg/100 g (U. pumila). High concentrations of rutin, quercetin 3‐O‐glucoside, and kaempferol derivatives were present in U. laevis, U. castaneifolia, and U. pumila, respectively. Furthermore, the fruit extracts of U. americana, U. castaneifolia, U. davidiana, and U. pumila showed higher antioxidant activity. These results suggest that fruits of these species can be used as bioresources for the extraction of the corresponding functional compounds. This work provides informative data and can be an important reference for future research on elm fruits as a renewed food resource. [ABSTRACT FROM AUTHOR]

The effects of pycnogenol on plasma lipids are controversial. A systematic review and meta-analysis of clinical trials were conducted to obtain a conclusive result in humans. PubMed, Scopus, and Google Scholar were systematically searched until March 2018, to explore the clinical trials that examined the effect of pycnogenol supplementation on lipid parameters among adult human. Methodological quality of the eligible studies was evaluated using the Cochrane Collaboration's tool. To estimate the effect size, changes in blood lipids were implemented. Results were pooled using a random effects model. Potential sources of heterogeneity were explored by subgroup analysis. A systematic review and meta-analysis of 14 clinical trials with 1,065 participants suggested a significant increase in plasma concentration of high density lipoprotein cholesterol (HDL-C; 3.27 mg/dL; 95% CI [0.19, 6.36]; p = 0.038). In contrast, plasma levels of total cholesterol (TC; -4.45 mg/dL, 95% CI [-11.24, 2.34]; p = 0.199), triacylglycerol (TAG; -3.64 mg/dL; 95% CI [-17.89, 10.61]; p = 0.616), and low density lipoprotein cholesterol (LDL-C; -3.61 mg/dl; 95% CI [-8.76, 1.55]; p = 0.171) were not altered. Adjustment for confounding variables was poor in included studies. Also, these studies did not assess dietary lipid intake. The results indicate that pycnogenol supplementation improves levels of HDL-C; however, the changes in TC, TAG, and LDL-C were not clinically relevant. Since there are few phytochemicals that have a significant increasing effect on HDL-C levels, pycnogenol may have important role in prevention of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The aim of the present study was a comparative investigation of water and 70% ethanol extracts derived from yellow and red onion (Allium cepa L.) peels against diabetes and diabetic complications. The total phenolic contents (TPCs) and total flavonoid contents (TFCs) of each cultivar, measured to assess phytochemical characteristics, showed a direct correlation with the in vitro antioxidant effects. Among the two captives, the yellow onion peel extract showed higher antioxidant activity than red one. However, all extracts exhibited significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (IC50; 0.30–0.86 μg/ml), showing water extracts more potent (IC50; approximately 0.3 μg/mL), than the 70% ethanol extracts (IC50; approximately 0.8 μg/ml). Similarly, in insulin‐resistant HepG2 cells, all extracts enhanced the glucose uptake and reduced the expression of PTP1B in a concentration‐dependent manner, water extract displaying better activity. Our results overall suggest that in vitro antioxidant and antidiabetic potentials vary among red and yellow cultivars and extracting solvents, which could therefore be a promising strategy to prevent diabetes and associated complications. The present study provides an insight into the bioactivity of waste onion peel toward diabetes and diabetic complications. Furthermore, the varying degree of TPC and TFC in different solvent extracts of two cultivars was compared and correlated with their potency. Overall result of the present study demonstrated onion peel as good food source to prevent diabetes and diabetic complications. [ABSTRACT FROM AUTHOR]

Abstract: Among flavonoid derivatives, tiliroside is a flavonoid contained in several edible plants or specific plant parts (fruits, leaves, or roots). These parts are often widely used as both food and medicines, in the treatment of various ailments and, in some cases, as food supplements. Considering the easy access to many publications concerning tiliroside and the lack of a review that summarizes the current progress in studies on its safety, efficacy, and presence in the plant kingdom, we present here a review paper on tiliroside and its principal derivatives. The paper also highlights the basic knowledge regarding this molecule, its derivatives, and the analytical approaches used for extraction and quantification, as well as reports on the biological activities against different key enzymes linked to various human diseases. The reported information is also devoted to highlighting the concept “learn from nature to discover new products,” particularly in the development of new drugs, food supplements, and nutraceuticals, starting from a natural lead compound such as tiliroside and improving its biological activities (and selectivities) against a specific target for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Abstract: Flavonoids are plant‐derived dietary components with a substantial impact on human health. Research has expanded massively since it began in the 1930s, and the complex pathways involved in bioavailability of flavonoids in the human body are now well understood. In recent years, it has been appreciated that the gut microbiome plays a major role in flavonoid action, but much progress still needs to be made in this area. Since the first publications on the health effects of flavonoids, their action is understood to protect against various stresses, but the mechanism of action has evolved from the now debunked simple direct antioxidant hypothesis into an understanding of the complex effects on molecular targets and enzymes in specific cell types. This review traces the development of the field over the past 8 decades, and indicates the current state of the art, and how it was reached. Future recommendations based on this historical analysis are (a) to focus on key areas of flavonoid action, (b) to perform human intervention studies focusing on bioavailability and protective effects, and (c) to carry out cellular in vitro experiments using appropriate cells together with the chemical form of the flavonoid found at the site of action; this could be the native form of compounds found in the food for studies on digestion and the intestine, the conjugated metabolites found in the blood after absorption in the small intestine for studies on cells, or the chemical forms found in the blood and tissues after catabolism by the gut microbiota. [ABSTRACT FROM AUTHOR]

Immune dysfunction is caused by various factors, including changes in relevant immune regulators and environmental stress. Immune system imbalance leads to a variety of diseases in humans. Nutrition may play an essential role in immunity by interfering with proinflammatory cytokine synthesis, immune cell regulation, and gene expression. Polyphenols, one of many categories of natural substances, exhibit a range of biological activities. Polyphenols promote immunity to foreign pathogens via various pathways. Different immune cells express multiple types of polyphenol receptors that recognise and allow cellular uptake of polyphenols, which subsequently activate signalling pathways to initiate immune responses. Furthermore, the polyphenols curcumin and epigallocatechin gallate can induce epigenetic changes in cells. In summary, polyphenols can be used to regulate intestinal mucosal immune responses, allergic diseases, and antitumour immunity. [ABSTRACT FROM AUTHOR]

Aim: To develop and assess the validity and reproducibility of a food frequency questionnaire (FFQ) to measure total flavonoid intake, and individual flavonoid subclasses, in older adults. Methods: Retrospective analysis of flavonoid intake in older adults informed the development of a FFQ to measure flavonoid intake and determine the flavonoid subclasses consumed (anthocyanins, flavan‐3‐ols, flavones, flavonols and flavanones). Older adults (n = 42, mean age 75.3 ± 8.6 years) attended two interviews 1 month apart where anthropometrics (height and weight), blood pressure (BP), demographic data and a 93‐item self‐administered FFQ were collected. A 4‐day food record (FR) was randomly administered between the two interview dates, and each food item was assigned a flavonoid and flavonoid subclass content using the United States Department of Agriculture flavonoid database. The criterion validity and reproducibility of the FFQ was assessed against a 4‐day FR using the Wilcoxon signed‐rank sum test, Spearman's correlation coefficient (r), Bland‐Altman Plots and Cohen's kappa. Results: Total flavonoid intake was determined (median intake FFQ = 919.3 mg/day, FR = 781.4 mg/day). Tests of validity indicated that the FFQ consistently overestimated total flavonoid intake compared with the 4‐day FR. There was a significant difference in estimates between the FFQ and the 4‐day FR for total flavonoid intake (Wilcoxon signed‐rank sum P < 0.001; Bland‐Altman plots indicated large bias and wide limits of agreement), but they were well correlated (Spearman's r 0.93, P < 0.001; Cohen's kappa κ = 0.619, P < 0.001). For individual flavonoid subclasses, the tests of validity indicated greater discrepancy compared with 4‐day FR. The FFQ showed high reproducibility for estimating total flavonoid intake (FFQ1vsFFQ2: Wilcoxon signed‐rank sum test, P > 0.05; Spearman's r 0.91, P < 0.001; Bland‐Altman plots visually showed small, non‐significant bias and wide limits of agreement; and Cohen's kappa κ = 0.619, P < 0.001), with a small mean percentage difference (6.7%). For individual flavonoid subclasses, the tests of reproducibility between FFQ1 and FFQ2 showed similarly high reproducibility. Conclusions: The developed FFQ appears suitable for satisfactorily ranking individuals according to total flavonoid intake. The FFQ shows limitations for estimating absolute total flavonoid intake and intake of flavonoid subclasses in comparison to a 4‐day FR in terms of overestimating intake. Refinement and further validation of this tool may be required. [ABSTRACT FROM AUTHOR]

Animal feed provides a range of antioxidants that help the body building an integrated antioxidant system responsible for a prevention of damaging effects of free radicals and products of their metabolism. Vitamin E is considered to be the main chain-breaking antioxidant located in the membranes and effectively protecting them against lipid peroxidation. Recently, various polyphenol compounds, especially flavonoids, have received substantial attention because of their antioxidant activities in various in vitro systems. However, it was shown that flavonoid compounds are poorly absorbed in the gut and their concentrations in target tissues are too low to perform an effective antioxidant defences. The aim of the present paper is to review existing evidence about possible roles of various plant extracts provided with the diet in animal/poultry nutrition with a specific emphasis to their antioxidant activities. [ABSTRACT FROM AUTHOR]

Nowadays dietary flavonoids attract considerable attention in the prevention of cardiovascular diseases, even though the definitive structure–activity relationships (SARs) of flavonoids are not completely understood. This review exclusively aims to summarize recent evidence for the correlation between structural features of dietary flavonoids and effects on vascular endothelial function (EF). In human studies, the diets rich in one of six flavonoid subclasses namely, flavonol, flavone, flavanol, flavanone, anthocyanin, and isoflavone were reported to have positive effects on EF. However, the clinical evidence supporting SAR establishment was limited and often inconclusive. In in vitro models, the evidence for the activities of metabolized and unmetabolized flavonoids in three protective pathways of EF: nitric oxide bioavailability, induction of antioxidant enzymes, and anti‐inflammation are highlighted. The specific structural characteristics favorable in modulation of each pathway are summarized. Nevertheless, the roles of the substituent property of flavonoid metabolites on endothelial cells function remain to be investigated. Practical applications: Due to the potential benefits for cardiovascular health, dietary flavonoids have come into the focus of utilization as a nutraceutical ingredient in food and pharmaceutical industries. Since there are many hundreds of flavonoids in human diets, thus it is very necessary to known if specific structural motifs could confer some flavonoids with higher cardiovascular bioactivity than others. The discussion on SARs for protecting vascular endothelial function will give us important information on utilization of flavonoids in human precise nutrition. [ABSTRACT FROM AUTHOR]