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Relative impact of flavonoid composition, dose and structure on vascular function: A systematic review of randomised controlled trials of flavonoid-rich food products
Molecular Nutrition & Food Research
Abstract
Previous systematic reviews suggest beneficial effects of flavonoids on biomarkers of cardiovascular disease (CVD) risk, but have overlooked the impact of dose response or food complexity. The aim of the present study was to examine the relative impact of composition, flavonoid structure and dose.
MEDLINE, EMBASE and Cochrane were searched for randomised controlled trials (RCTs) of flavonoids or flavonoid-rich foods/extracts. Flavonoid composition was established using United States Department of Agriculture (USDA) and Phenol-Explorer databases. Effects of six flavonoid subgroups on endothelial function (flow-mediated dilation; FMD), and systolic and diastolic blood pressures were assessed by random effects meta-analyses and regression analyses. Meta-analyses of combined flavonoid subclasses showed significant improvements in FMD (chronic, 0.73% (0.17, 1.30) 14 RCTs; acute, 2.33% (1.58, 3.08) 18 RCTs) and blood pressures (systolic, -1.46 mmHg (-2.38, -0.53) 63 RCTs; diastolic, -1.25 mmHg (-1.82, -0.67) 63 RCTs). Similar benefits were observed for the flavan-3-ol, catechol flavonoids (catechins, quercetin, cyanidin etc.), procyanidins, epicatechin and catechin subgroups. Dose-response relationships were non-linear for FMD (R(2) ≤ 0.30), with greater associations observed when applying polynomial regression analyses (R(2) ≤ 0.72); there was no indication of a dose response for blood pressure.
The present analysis suggests that flavonoid bioactivity does not follow a classical linear dose-response association and this may have important biological implications.
... These include the flavonols, flavan-3-ols (monomers and polymers) and anthocyanidins. A recent systematic review and meta-analysis of randomised controlled trials of flavonoid-rich food products has attempted to explore the effects of different flavonoid classes on vascular function [30]. All (combined) flavonoid subclasses resulted in a significant improvement in flow-mediated dilatation by approximately 30% in acute studies and approximately 10% in short-term studies of regular ingestion of the flavonoids [30]. ...
... A recent systematic review and meta-analysis of randomised controlled trials of flavonoid-rich food products has attempted to explore the effects of different flavonoid classes on vascular function [30]. All (combined) flavonoid subclasses resulted in a significant improvement in flow-mediated dilatation by approximately 30% in acute studies and approximately 10% in short-term studies of regular ingestion of the flavonoids [30]. These effects would be consistent with the suggested benefit of red wine flavonoids in acute studies, with less support for benefit in studies of regular ingestion [14,30]. ...
... All (combined) flavonoid subclasses resulted in a significant improvement in flow-mediated dilatation by approximately 30% in acute studies and approximately 10% in short-term studies of regular ingestion of the flavonoids [30]. These effects would be consistent with the suggested benefit of red wine flavonoids in acute studies, with less support for benefit in studies of regular ingestion [14,30]. Kay et al [30] also explored estimated effects of individual flavonoid subclasses. ...
... In addition to the lack of evidence, some issues should be taken into account in the study of the relationship between total flavonoids and their subclasses and hypertension risk: (1) Differences in the combinations of flavonoids consumed across the globe may result from differences in dietary cultures and their corresponding dietary patterns; this issue is exacerbated by the fact that most previous studies looking into this issue have been conducted in Western populations; (2) Dietary assessments may be confounded by measurement errors, and dietary preferences could be changed over the course of the study. However, only single dietary assessment data were used in these studies; (3) Furthermore, a systematic review of the relationship between flavonoids and vascular function pointed to the possibility that it does not follow a classical linear dose-response association [9]. Thus, the shape of the relationship (linearity or non-linearity) should be tested; (4) Finally, a few previous studies showed that the association of dietary factors with hypertension risk differed according to obesity status [10,11]. ...
... Linearity was tested by treating the median cumulative average intake of total flavonoid and their subclasses in each quartile as a continuous variable. To consider a possible curvilinear association suggested by a systematic review of the relationship between flavonoids and vascular function [9], we accounted for the inherent nonlinearity of the fitted categorical model by comparing the deviance difference between the linearity model on 1 degree of freedom (d.f.) and ordered [29]. The associations between flavonoids and hypertension risk were reanalyzed in each stratum of obesity status (normal and overweight/obese groups). ...
In this study, we aimed to investigate the prospective associations and their shapes between the dietary intake of total flavonoids and their seven subclasses and hypertension risk in a prospective cohort, the KoGES_CArdioVascular disease Association Study (CAVAS), and to consider obesity status as an additional factor. A total of 10,325 adults aged 40 years and older were enrolled at baseline, and 2159 patients were newly diagnosed with hypertension during a median follow-up of 4.95 years. Cumulative dietary intake was estimated using a repeated food frequency questionnaire. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were estimated using modified Poisson models with a robust error estimator. We observed nonlinear inverse associations between total and seven subclasses of flavonoids and hypertension risk, although there was no significant association between total flavonoids and flavones with hypertension risk in the highest quartile. For men, these inverse associations tended to be pronounced in the high BMI group, particularly for anthocyanins and proanthocyanidins [IRR (95% CI) in overweight/obese men: 0.53 (0.42–0.67) for anthocyanins; 0.55 (0.42–0.71) for proanthocyanidins]. Our results suggested that consumption of dietary flavonoids may not be dose-responsive but is inversely associated with hypertension risk, particularly among overweight/obese men.
... GSOP alone either did not change ( LUT treatment alone on IPEC-J2 cells at 25 and 100 μg/mL did not influence IC ROS production; however, 50 μg/mL LUT treatment resulted in a significantly lower ROS level compared to the control (p < 0.001). A possible explanation of this finding is that there might be nonlinear dose effects of flavonoids as stated by Kay et al. [28]. LUT treatment alone on IPEC-J2 cells at 25 and 100 µg/mL did not influence IC ROS production; however, 50 µg/mL LUT treatment resulted in a significantly lower ROS level compared to the control (p < 0.001). ...
... LUT treatment alone on IPEC-J2 cells at 25 and 100 µg/mL did not influence IC ROS production; however, 50 µg/mL LUT treatment resulted in a significantly lower ROS level compared to the control (p < 0.001). A possible explanation of this finding is that there might be nonlinear dose effects of flavonoids as stated by Kay et al. [28]. All concentrations of LUT showed potent antioxidant activity against both E. coli and S. Typhimurium LPS treatments. ...
Beneficial effects of flavonoids are widely known in human medicine, but less information is available about their veterinary usage. Based on their antioxidant and antibacterial activity, proanthocyanidins (PAs) and luteolin (LUT) might be used in the prevention and treatment of gastrointestinal infections in swine. In this study, in vitro beneficial effects of grape seed oligomeric proanthocyanidins (GSOPs) and LUT were investigated against bacterial endotoxin (LPS)-induced oxidative stress in IPEC-J2 porcine epithelial intestinal cells. Furthermore, antibacterial effects of GSOP and LUT were assessed against field isolates of Escherichia coli and Salmonella enterica ser. Typhimurium. Both GSOP and LUT were found to possess potent in vitro antioxidant activity in LPS-treated IPEC-J2 cells; furthermore, they showed a bacteriostatic effect against the tested bacterial strains of porcine origin. Both flavonoids seem to be effective in the protection of porcine intestinal epithelial cells against Gram-negative bacteria in vitro, but further in vivo studies are necessary to confirm these activities and to establish their optimal dosage regimen for future usage in veterinary practice.
... In the latter case, the potency of blackcurrant juices to induce vasorelaxation at volume ratio 1% correlated significantly with their total anthocyanin content and with their DG, DR, CyR, and MG contents. Such differences in vascular reactivity according to the volume ratio might also be related to human data indicating that flavonoid bioactivity, as reflected by in vivo endothelial function, does not follow a classical linear dose-response curve [41]. It is also possible that the rat aorta and porcine coronary artery differ markedly as regards their vascular reactivity. ...
... Even if endothelium-dependent vasodilation in both experimental models and humans have been reported after the intake of anthocyanin-rich fruit juices [23], large-scale clinical studies are needed to further and better explore in humans the beneficial endothelium-dependent cardiovascular effects of vegetable and fruit juice intake [52] and hence of polyphenols present in these foods [41]. This requires evaluating in vivo endothelial function in three with the measurement of plasma concentrations of both polyphenol metabolites by HPLC-MS/MS [48] and NO. ...
The real impact of polyphenol-rich vegetable and fruit juice intake on cardiovascular health remains a matter of controversy. In the present study, rat aorta segments immersed in an organ bath (OB) were used to explore whether the total polyphenol content and/or individual phenolic compound contents of 22 commercial vegetable (n = 3) and fruit juices [(citrus (n = 5), berries (n = 10), apple (n = 2), pineapple (n = 2)] might be associated with vascular tone. Red juices (particularly blackcurrant) and lemon juice caused the most marked vasorelaxation, its amplitude being endothelium dependent or not according to the volume ratio of juice to initial OB solution Vjuice/VOBS). At volume ratios 5% and 10%, both the juice and OB total polyphenol for all juices and total anthocyanin contents for berry juices significantly correlated with aorta vasorelaxation intensity. This was not the case for total or individual flavonols (except kaempferol) or for total or individual flavanols (except epigallocatechin gallate). If one relates our measured concentrations of individual phenolic compounds in OB to what is known about their physiological concentrations, and given our evidenced correlations between compound concentrations and vasorelaxation intensity, kaempferol, epigallocatechin gallate and peonidin-3-O-glucoside seem to emerge as the interesting phenolic compounds likely to be responsible for the potent vasorelaxation observed with fruit juices, and more particularly blackcurrant ones. Clinical investigation is required, however, to confirm our observations.
... Diet was self-reported, and is also associated with measurement error, as it is possible that some participants were misclassified in terms of their exposure. Although our study did not incorporate all food items originally used by Shivappa et al. for DII calculation, such as garlic, known for its anti-inflammatory properties [54], we believe that the absence of these compounds likely had a minimal impact on the accuracy of the DII, as our results are consistent with previous research [42,55,56] and most of these parameters have a low frequency of consumption in the Mexican population [31]. ...
Background:
The relationship between the dietary inflammatory index and blood pressure has been evaluated in European and American populations. This association remains unexplored in Mexico, where outcomes may differ due to the populace's ancestral heritage and its diverse dietary habits.
Methods:
We used the Health Workers Cohort Study (2004 to 2018). DII intake was assessed using a food frequency questionnaire. Blood pressure was measured following standardized procedures and techniques. Fixed-effects linear regression and Cox regression models were utilized as the statistical approaches.
Results:
In the first approach, we observed a positive association between changes in DII intake and changes in both systolic (SBP β: 3.23, 95% CI 1.11, 5.34) and diastolic blood pressure (DBP β: 1.01, 95% CI -0.43, 2.44). When stratified by hypertension, these associations were magnified in participants with hypertension (SBP β: 6.26, 95% CI 2.63, 9.89; DBP β: 1.64, 95% CI -0.73, 4.02). In the second approach, interactions between sex and age categories were explored. Participants in the highest DII category were associated with an increased risk of hypertension, particularly among young women (HR: 3.16, 95% CI 1.19, 8.43).
Conclusions:
Results suggest that a pro-inflammatory diet is associated with an increase in blood pressure over time among Mexican population.
... In contrast, in addition to FMD, this study demonstrated a significant improvement in endothelial function, as indicated by RHI. In addition, this study's subgroup analysis was consistent with another similar study (Kay et al., 2012), showing that acute intervention was more effective than chronic intervention in increasing the response effect of FMD. This divergence between this study and others lies in the intervention; previous studies used anthocyanin-rich or flavonoid-rich foods/extracts, whereas the present study used blueberries. ...
Introduction: Endothelial dysfunction indicates blood vessel injury and is a risk factor for cardiovascular diseases. Blueberry has been approved for its benefits on human health, especially on cardiovascular function. However, its effect on endothelial function remains unclear. We conducted a systematic review and meta-analysis to explore the impact of blueberries on endothelial function in adults.
Methods: We searched PubMed, Web of Science, Embase, and the Cochrane Library, 16 studies were included in the systematic review, and 11 were used for the meta-analysis. Data associated with endothelial function were extracted and pooled as mean differences (MD) with 95% confidence intervals (CI).
Results: Blueberry consumption significantly improved flow-mediated dilation (FMD) by 1.50% (95% CI: 0.81, 2.20; I² = 87%) and reactive hyperemia index (RHI) by 0.26 (95% CI: 0.09, 0.42; I² = 72%). A significant decrease in diastolic blood pressure (DBP) was also observed (MD: −2.20 mm Hg; 95% CI: −4.13, −0.27; I² = 11%). Subgroup analysis indicated a significant decrease in blood pressure (Systolic blood pressure [SBP]: −3.92 mmHg; 95% CI: −6.88, −0.97; I² = 20% and DBP: −2.20 mmHg; 95% CI: −4.13, −0.27; I² = 11%) in the smoking population. However, SBP levels (MD: −1.43 mm Hg; 95% CI: −3.11, 0.26; I² = 20%) and lipid status (high-density lipoprotein cholesterol [HDL-C]: 0.06; 95% CI: −0.04, 0.16; I² = 77%; low-density lipoprotein cholesterol [LDL-C]: 0.05; 95% CI: −0.14, 0.24; I² = 0%) did not significantly improve.
Conclusion: Blueberry intervention improved endothelial function and DBP. Subgroup analysis revealed a notable improvement in blood pressure among the smoking population. However, no significant effects were observed on SBP, HDL-C, and LDL-C levels. Future research should delve into the mechanisms of endothelial improvement and verify blood pressure reduction in specific subpopulations through large-scale trials.
Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/, Identifier CRD42023491277.
... These gut microbiota-derived metabolites can be absorbed by the enterocytes and be further metabolized by Phase I and Phase II metabolic reactions in the liver before entering general circulation [6]. 2 of 25 Flavonoids are among the best studied plant food bioactives in terms of their healthpromoting properties. Human studies have shown that a diet rich in flavonoids can reduce type 2 diabetes risk [7], improve insulin sensitivity and blood lipids [8], and have beneficial effects on vascular function [9]. Recently, a long-term, large-scale, randomized, doubleblind, placebo-controlled trial with cocoa extract supplementation [500 mg flavanols/d, including 80 mg (−)-epicatechin] showed a significant reduction in cardiovascular disease death by 27% among older adults [10]. ...
Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 candidate DEGs and 42 candidate URs, while subsequent functional analyses and a search of the literature identified 20 top priority candidate genes: ALDH2, APOE, CAPZA1, CYP11B2, GNA13, IL6, IRF5, LDLR, LPL, LSP1, MKNK1, MMP3, MTHFR, MYO6, NCR3, PPARG, SARM1, TCF20, TCF7L2, and TNF. In conclusion, this integrated analysis identifies important genes to design future nutrigenetic studies for development of precision nutrition for polyphenols.
... 120 Further metadata analysis indicated that endothelial function increased linearly to an intake of ≤500 mg total cocoa polyphenols, after which a decrease was observed at higher intakes, 121 and dose−response relations were nonlinear between endothelial function increase and flavonoid dose. 122 However, the effect of longer-term consumption of polyphenols including flavonols on endothelial function as well as other bioactivities warrant further investigations to recommend what "doses" of specific dietary Journal of Agricultural and Food Chemistry pubs.acs.org/JAFC Review components should be consumed to maximize the health benefit of interested biofunctional agents. ...
Consumption of fruits and vegetables has been associated with a reduced risk of multiple diseases, such as metabolic disorders. Flavonols are the most ubiquitous flavonoids in fruits and vegetables. However, dietary flavonols exhibit a general low oral bioavailability for their extensive biotransformation mediated by phase II enzymes in enterocytes and liver as well as by microbiota in the gut lumen. In this context, flavonols have brought attention to a paradox between low bioavailability and health-promoting effects. Flavonols are often transformed prior to absorption, which could change their biological activity. Compared to their parent compounds, the corresponding metabolites of flavonols in vivo might exhibit similar or higher intrinsic bioactivities, or perhaps a decreased efficacious effectiveness. Indeed, a growing body of evidence from biological function studies of metabolites supports the positive and significant contribution of in vivo metabolic processes, particularly conversion mediated by gut microbiota, to the health-promoting benefits of flavonols. As such, further understanding of the metabolic fate of flavonols and biological activities of their metabolites as well as the possible impact of microbiota-mediated conversion on the bioactivity is of great significance to guide a rational diet with flavonol-rich fruits and vegetables and/or flavonol-containing functional foods.
... This high dosage may reflect the poor bioavailability of quercetin aglycone administered as a supplement. Another systematic review, which examined 18 randomized controlled trials concerning the effects of flavonoid-rich food products on endothelial function, showed that catechol-type flavonoids, including quercetin, improved FMD, albeit with a non-linear dose-response relationship [167]. In addition, several small-scale intervention studies have explored inflammation-related biomarkers as endpoints for the effectiveness of quercetin supplementation. ...
Quercetin is a monomeric polyphenol of plant origin that belongs to the flavonol-type flavonoid subclass. Extensive studies using cultured cells and experimental model animals have demonstrated the anti-atherosclerotic effects of dietary quercetin in relation to the prevention of cardiovascular disease (CVD). As quercetin is exclusively present in plant-based foods in the form of glycosides, this review focuses on the bioavailability and bioefficacy of quercetin glycosides in relation to vascular health effects. Some glucose-bound glycosides are absorbed from the small intestine after glucuronide/sulfate conjugation. Both conjugated metabolites and deconjugated quercetin aglycones formed by plasma β-glucuronidase activity act as food-derived anti-atherogenic factors by exerting antioxidant, anti-inflammatory, and plasma low-density lipoprotein cholesterol-lowering effects. However, most quercetin glycosides reach the large intestine, where they are subject to gut microbiota-dependent catabolism resulting in deglycosylated aglycone and chain-scission products. These catabolites also affect vascular health after transfer into the circulation. Furthermore, quercetin glycosides may improve gut microbiota profiles. A variety of human cohort studies and intervention studies support the idea that the intake of quercetin glycoside-rich plant foods such as onion helps to prevent CVD. Thus, quercetin glycoside-rich foods offer potential benefits in terms of cardiovascular health and possible clinical applications.
... In epidemiologic and clinical studies, categories of phenolic compounds are increasingly promoted to help manage a healthy BP due to the positive correlations with a plantbased diet rich in whole grains, fruits, and vegetables. For example, Kay et al. [80] classified phenolics by flavonoid category and found a significant reduction in SBP (mean difference, −1.46 mmHg; 95% CI, −2.38, −0.53) and DBP (mean difference, −1.25 mmHg; 95%CI, −1.82, −0.67) when data across all flavonoids were pooled. Subgroup analyses indicate that this positive response was mainly driven by epicatechin, quercetin, and procyanidins. ...
Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) and cognitive decline. Elevations in blood pressure (BP) leading to HTN can be found in young adults with increased prevalence as people age. Oats are known to decrease CVD risk via an established effect of β-glucan on the attenuation of blood cholesterol. Many past studies on CVD and oats have also reported a decrease in BP; however, a thorough assessment of oats and BP has not been conducted. Moreover, oats deliver several beneficial dietary components with putative beneficial effects on BP or endothelial function, such as β-glucan, γ-amino butyric acid (GABA), and phytochemicals such as avenanthramides. We conducted a comprehensive search for systematic reviews, meta-analyses, and clinical intervention studies on oats and BP and identified 18 randomized controlled trials (RCTs) and three meta-analyses that supported the role of oats in decreasing BP. Emerging data also suggest oat consumption may reduce the use of anti-hypertensive medications. The majority of these studies utilized whole oats or oat bran, which include a vast array of oat bioactives. Therefore, we also extensively reviewed the literature on these bioactives and their putative effect on BP-relevant mechanisms. The data suggest several oat components, such as GABA, as well as the delivery of high-quality plant protein and fermentable prebiotic fiber, may contribute to the anti-HTN effect of oats. In particular, GABA is enhanced in oat sprouts, which suggests this food may be particularly beneficial for healthy BP management.
... Flavonoids have been considered as prospective anticancer agents due to their potential to arrest cell cycle, downregulate mutant p53 protein, and inhibit Ras protein expression. The monomers, extracts and derivatives of flavonoids ( Fig. 4.8 were applied to phase II or phase III clinical trial studies (Bisol et al., 2020;Kay et al., 2012). ...
Natural flavonoids as the glycoside forms in vegetables and fruits are the most important phytochemicals in diets. Flavonoid glycosides are hydrolyzed both in the oral cavity and intestine to produce more bioactive and absorbable aglycones, which is meaningful to the health benefits of flavonoids. Here the structure-stability relationship/structure-antioxidant activity relationships of flavonoids were summarized. Although natural flavonoids displayed various bioactivities in cell and animal levels; however, their clinical outcomes are still limited. Isoquercetin, quercetin, EGCG, and genistein are hot molecules in clinical trials. It is really important to carry out large scale clinical and human studies in order to evaluate flavonoids benefits.
... These fluctuating effects were common in administering herbs containing several active compounds. The effect depended on the dose, chemical molecular composition, and the amount of active compound [42]. In this study, the analysis of TGF-β1 and TRAIL-R2 expression was carried out specifically in a-HSC. ...
BACKGROUND: Moringa oleifera (MO) exhibits hepatoprotective properties and provides an anti-liver fibrosis effect. However, its mechanism related to the anti-liver fibrosis effect was still unclear. AIM: The objective of this study was to explain the mechanism of liver fibrosis prevention by MO through hepatic stellate cells (HSCs). MATERIALS AND METHODS: The liver fibrosis model was induced by the intraperitoneal injection of 10% CCl4 twice a week at a one cc/kg BW dose for 12 weeks and followed by a quantity of 2 cc/kg BW for the past 2 weeks. Ethanol extract of MO leaves (150, 300, and 600 mg/kg) was orally administered daily. Double immunofluorescence staining and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis were applied to analyze the markers involved in HSCs activation and a-HSC apoptosis. RESULTS: The results showed that the administration of MO could reduce transforming growth factor-β and nuclear factor-kappa B (NFκB), increase the expression of tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 and caspase-3, and increase the number of apoptosis a-HSCs. CONCLUSION: This study showed that the ethanol extract of MO leaves could inhibit liver fibrosis by inhibiting HSCs activation and inducing of a-HSCs apoptosis through the extrinsic pathway.
... Evidence from cohort studies and pivotal research demonstrated the ability of phytocompounds to constantly modulate vasoprotective factors. ese factors regulate the function of the endothelial barrier [2,3]. ese compounds show promise in the management of cardiovascular disease. ...
Vascular endothelial dysfunction is characterized by an imbalance of vasodilation and vasoconstriction, deficiency of nitric oxide (NO) bioavailability and elevated reactive oxygen species (ROS), and proinflammatory factors. This dysfunction is a key to the early pathological development of major cardiovascular diseases including hypertension, atherosclerosis, and diabetes. Therefore, modulation of the vascular endothelium is considered an important therapeutic strategy to maintain the health of the cardiovascular system. Epidemiological studies have shown that regular consumption of medicinal plants, fruits, and vegetables promotes vascular health, lowering the risk of cardiovascular diseases. This is mainly attributed to the phytochemical compounds contained in these resources. Various databases, including Google Scholar, MEDLINE, PubMed, and the Directory of Open Access Journals, were searched to identify studies demonstrating the vascular protective effects of phytochemical compounds. The literature had revealed abundant data on phytochemical compounds protecting and improving the vascular system. Of the numerous compounds reported, curcumin, resveratrol, cyanidin-3-glucoside, berberine, epigallocatechin-3-gallate, and quercetin are discussed in this review to provide recent information on their vascular protective mechanisms in vivo and in vitro. Phytochemical compounds are promising therapeutic agents for vascular dysfunction due to their antioxidative mechanisms. However, future human studies will be necessary to confirm the clinical effects of these vascular protective mechanisms.
... Other flavonoids found in Korean pears (P. pyrifolia Chuhwangbae) include quercetin 3-O-glucoside, its aglycone quercetin [18,45], and dulcisflavan, a catechol [46]. Quercetin 3-O-glucoside is one of the dominant flavonols among leaves and fruits of pears [16]. ...
Background
Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia.
Methods
We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears.
Results
We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro , in vivo , and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, −hyperlipidemic, −inflammatory, −mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM 2.5 among high susceptible people with multiple underlying diseases.
Conclusion
For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.
... This is presumably due to saturation of hesperidin absorption and elimination mechanisms. Some studies suggested that natural compounds like flavonoids can show unexpected results, in which lower doses demonstrate better outcomes than higher doses (25,26). ...
Flavonoids have demonstrated beneficial effects in fatty liver disease (FLD). Consumption of flavonoids is associated with several health benefits via their antioxidant and anti-inflammatory activities. The current study aimed to investigate hesperidin and myricetin as new candidates for FLD therapy. Five-week-old female ICR mice were provided a high fat diet (HFD) 60 kcal % fat of total food and daily intragastrically administered ethanol (0.5 g/kg/day) in combination with fenofibrate (40 mg/kg/day) or flavonoids, hesperidin or myricetin (50 and 200 mg/kg/day), for 60 consecutive days. Hepatic histomorphology was observed with oil red O (ORO) staining along with hepatic triglyceride (TG) level, activity of antioxidative enzymes, and mRNA expression of metabolic, antioxidative, and inflammatory genes, including peroxisome proliferator activated receptor-alpha and -gamma 2 (Ppara and Pparg2), sterol regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acaca), fatty acid synthase (Fasn), CD36 molecules (Cd36), catalase (Cat), superoxide dismutase 1 and 2 (Sod1 and Sod2), glutathione peroxidase 1 (Gpx1), nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Nfkb1), tumor necrosis factor-alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2). Fenofibrate, hesperidin, and myricetin improved hepatic histomorphology, restored expression of metabolic genes, improved antioxidative system, and suppressed inflammatory pathways. Interestingly, hesperidin attenuated TG level and down-regulated Ccl2 expression at low dose and reinstated Cat expression better than myricetin. These findings confirm that hesperidin is a promising candidate for FLD therapy.
... 21 Brachial artery flow-induced dilation is an indicator of endothelial function, and several studies have consistently shown that tea and other flavonoid-rich foods have a positive effect on it. 22,23 Tea and its flavonoids improve endothelial nitric oxide synthase activity by enzyme phosphorylation. 24 According to Saito et al., 25 theaflavins can alter hemodynamics in both rats and healthy people. ...
BACKGROUND
Tea, second only to water, is one of the most regularly consumed drinks in the world. Its potentially beneficial effects on general health may be enormously important. Optical coherence tomography angiography (OCTA) now allows clinicians to examine the acute retinal morphological changes caused by black tea consumption. The purpose of this study was to investigate the acute impacts of a Camellia sinensis fermentation end‐product (black tea) on retinal microvasculature in healthy individuals using OCTA.
RESULTS
In this study, 60 healthy people were divided into two groups: group 1 (n = 30) received black tea (2 mg/250 mL of water) and group 2 (n = 30) received only 250 mL of water. Following consumption, AngioVue Analytics software automatically analyzed the foveal, parafoveal, perifoveal macular superficial and deep vascular plexus densities, foveal avascular zone (FAZ) area, FAZ perimeter and foveal vessel density in a 300 μm wide region around the FAZ (FD‐300). Male‐to‐female ratios were 19:11 and 15:15 in groups 1 and 2, respectively (P = 0.217). Mean age was 33.27 ± 7.92 years in group 1 and 31.00 ± 7.30 years in group 2 (P = 0.254). Changes in foveal, perifoveal and parafoveal macular vessel density between groups 1 and 2 were not statistically significant. In addition, no significant differences regarding FAZ, FAZ perimeter and FD‐300 were observed.
CONCLUSION
There were no acute effects of black tea on macular microcirculation in healthy individuals. The authors, however, believe that this study could serve as a model for future research on the relationship between regular tea consumption and general ocular physiology. © 2021 Society of Chemical Industry.
... Also, they are involved in inducing apoptosis of VSMCs by upregulation of p21, p53, and NF-κB, thus decreasing the risk of atherosclerosis development (Chen et al. 2016b). In a systematic review to analyze the flavonoid's impact on vascular function (Kay et al. 2012), it was found that they improved blood pressure and both acute and chronic flow-mediated (Heiss et al. 2010). Anthocyanin supplementation improved both acute and chronic FMD are improved with no improvement in the reactive hyperemia index. ...
Cardiovascular diseases (CVDs) have diverse physiopathological mechanisms with interconnected oxidative stress and inflammation as one of the common etiologies which result in the onset and development of atherosclerotic plaques. In this review, we illustrate this strong crosstalk between oxidative stress, inflammation, and CVD. Also, mitochondrial functions underlying this crosstalk, and various approaches for the prevention of redox/inflammatory biological impacts will be illustrated. In part, we focus on the laboratory biomarkers and physiological tests for the evaluation of oxidative stress status and inflammatory processes. The impact of a healthy lifestyle on CVD onset and development is displayed as well. Furthermore, the differences in oxidative stress and inflammation are related to genetic susceptibility to cardiovascular diseases and the variability in the assessment of CVDs risk between individuals; Omics technologies for measuring oxidative stress and inflammation will be explored. Finally, we display the oxidative stress-related microRNA and the functions of the redox basis of epigenetic modifications.
... SLRs using supplements found improved blood pressure and HDL cholesterol, flow mediated dilation, blood pressure, weight, and waist circumference; however, there was some inconsistency (i.e. some studies reported a significant effect; others reported no effect) for most of these outcomes, likely related to variations in sample and intervention characteristics (Akhlaghi et al. 2018;Amiot, Riva, and Vinet 2016;Farhat, Drummond, and Al-Dujaili 2017;Kay et al. 2012;Pot ı et al. 2019). ...
Dietary guidelines for many Western countries base their edible oil and fat recommendations solely on saturated fatty acid content. This study aims to demonstrate which nutritional and bioactive components make up commonly consumed edible oils and fats; and explore the health effects and strength of evidence for key nutritional and bioactive components of edible oils. An umbrella review was conducted in several stages. Food composition databases of Australia and the United States of America, and studies were examined to profile nutrient and bioactive content of edible oils and fats. PUBMED and Cochrane databases were searched for umbrella reviews, systematic literature reviews of randomized controlled trials or cohort studies, individual randomized controlled trials, and individual cohort studies to examine the effect of the nutrient or bioactive on high-burden chronic diseases (cardiovascular disease, type 2 diabetes mellitus, obesity, cancer, mental illness, cognitive impairment). Substantial systematic literature review evidence was identified for fatty acid categories, tocopherols, biophenols, and phytosterols. Insufficient evidence was identified for squalene. The evidence supports high mono- and polyunsaturated fatty acid compositions, total biophenol content, phytosterols, and possibly high α-tocopherol content as having beneficial effects on high-burden health comes. Future dietary guidelines should use a more sophisticated approach to judge edible oils beyond saturated fatty acid content.
... Treatment with the higher dose of 5-CQA (900 mg), however, did not show any significant differences with the placebo treatment, although the absorption of CGAs was higher in the 900-mg treatment than in the 450mg treatment. This nonlinear relation between coffee compounds and FMD, also observed in our present findings, was supported by several meta-analyses of randomized controlled trials which found that the relation between the doses of different types of polyphenols and FMD followed an inverted U-shape and that high doses of polyphenols could have smaller effects on endothelial function than lower doses (34,35). This observation has also been made in individual studies; for instance, 1 study testing the effects of different doses of a blueberry drink on FMD showed a comparable inverted U-shape, whereby the vascular response increased with increasing amounts, then reached a plateau and finally decreased at higher intakes (36). ...
Background
Epidemiological studies have reported lower risk of cardiovascular disease with moderate coffee consumption. In addition, emerging evidence indicates that consumption of coffee beverages enriched in chlorogenic acids (CGAs) may influence blood pressure and endothelial function, suggesting that the beneficial cardiovascular effect of coffee may relate to its CGA content.
Objectives
We conducted a double-blind randomized crossover trial to test the effect of acute consumption of a decaffeinated green coffee extract (DGCE), rich in CGAs, on endothelial function in healthy subjects.
Methods
We compared 3 different doses of DGCE (302, 604, and 906 mg, respectively) with a placebo. Endothelial function was defined as the percentage change in the internal diameter of the brachial artery in response to flow-mediated dilation (%FMD). In addition, we followed the plasma concentration-time profiles of 25 systemic CGA metabolites over 24 h after DGCE consumption and we explored the relation between systemic concentrations of CGAs and the effect on %FMD.
Results
The DGCE formulations containing different amounts of CGAs resulted in dose-proportional increases in overall total polyphenol concentrations. The systemic appearance of total CGAs was biphasic, in agreement with previous results suggesting 2 sites of absorption in the gastrointestinal tract. Compared with the placebo group, a significant FMD increase (>1%) was observed 8.5, 10, and 24 h after consumption of 302 mg DGCE (∼156.4 mg CGAs). The differences with placebo observed in the other 2 groups were not statistically significant. Evaluation of the relation between phenolic exposure and %FMD showed a positive tendency toward a larger effect at higher concentrations and different behavior of CGA metabolites depending on the conjugated chemical position.
Conclusions
We demonstrated an acute improvement in %FMD over time after ingestion of a DGCE, explained at least partly by the presence in the blood circulation of CGAs and their metabolites. This trial was registered at clinicaltrials.gov as NCT03520452.
... Evidence from many short-term trials in humans has suggested that flavonoids and, in particular, flavanol monomers and procyanidin may have a beneficial effect on blood pressure in humans [63]. In this review, we show the effect of grape seed proanthocyanidin on blood pressure in elderly Japanese women and the relation between proanthocyanidin intake and incidence of hypertension in a large prospective cohort of women. ...
Middle-aged and elderly women are affected by various symptoms and diseases induced by estrogen deficiency. Proanthocyanidins, widely present in many kinds of fruits and berries, have many beneficial effects, such as antioxidative, anti-inflammatory, and antimicrobial activities. We researched the effects of proanthocyanidins for middle-aged and elderly women, finding that it has been revealed in many clinical trials and cohort studies that proanthocyanidins contribute to the prevention of cardiovascular disease, hypertension, obesity, cancer, osteoporosis, and urinary tract infection, as well as the improvement of menopausal symptoms, renal function, and skin damage. Thus, proanthocyanidins can be considered one of the potent representatives of complementary alternative therapy.
... Low doses of luteolin increased p21 expression and high doses of luteolin decreased its expression in cancer cells [38]. These results suggest that flavonoid bioactivity does not follow a classical dose-dependent relation and it may have critical biological implications [39]. However, so far, there has been no report to accurately explain the opposite responses and their mechanisms according to the concentration of flavonoids such as ILG. ...
Human adipose-derived stem cells (hASCs) can be isolated from fat tissue and have attracted interest for their potential therapeutic applications in metabolic disease. hASCs can be induced to undergo adipogenic differentiation in vitro by exposure to chemical agents or inductive growth factors. We investigated the effects and mechanism of differentiating hASC-derived white adipocytes into functional beige and brown adipocytes with isoliquiritigenin (ILG) treatment. Here, we showed that hASC-derived white adipocytes could promote brown adipogenesis by expressing both uncoupling protein 1 (UCP1) and PR/SET Domain 16 (PRDM16) following low-dose ILG treatments. ILG treatment of white adipocytes enhanced the expression of brown fat-specific markers, while the expression levels of c-Jun N-terminal kinase (JNK) signaling pathway proteins were downregulated. Furthermore, we showed that the inhibition of JNK phosphorylation contributed to white adipocyte differentiation into beige adipocytes, which was validated by the use of SP600125. We identified distinct regulatory effects of ILG dose responses and suggested that low-dose ILG induced the beige adipocyte potential of hASCs via JNK inhibition.
... In addition, flavonoids demonstrate significant physiological and biochemical effects on mammals because of their unique chemical structures. Most flavonoids exhibit great antioxidant (Naderi et al., 2003), anti-inflammatory (Kim et al., 2004), antibacterial (Cushnie and Lamb, 2011), and anticancer (Ravishankar et al., 2013) activities; thus, they have been widely used in food, nutraceutical, and pharmaceutical industries (Kay et al., 2012;Georgiev et al., 2014;Hajimehdipoor et al., 2014). For example, apigenin can be used to treat high-fat and highfructose diet-induced metabolic syndrome by reducing leptin levels and increasing adiponectin levels . ...
Flavonoids are a class of secondary metabolites found in plant and fungus. They have been widely used in food, pharmaceutical, and nutraceutical industries owing to their significant biological activities, such as antiaging, antioxidant, anti-inflammatory, and anticancer. However, the traditional approaches for the production of flavonoids including chemical synthesis and plant extraction involved hazardous materials and complicated processes and also suffered from low product titer and yield. Microbial synthesis of flavonoids from renewable biomass such as glucose and xylose has been considered as a sustainable and environmentally friendly method for large-scale production of flavonoids. Recently, construction of microbial cell factories for efficient biosynthesis of flavonoids has gained much attention. In this article, we summarize the recent advances in microbial synthesis of flavonoids including flavanones, flavones, isoflavones, flavonols, flavanols, and anthocyanins. We put emphasis on developing pathway construction and optimization strategies to biosynthesize flavonoids and to improve their titer and yield. Then, we discuss the current challenges and future perspectives on successful strain development for large-scale production of flavonoids in an industrial level.
... This is not the first study that was unable to show a clear dose response effect of anthocyanin supplementation. For example, a review evaluating various flavonoid doses on vascular function did not observe any dose response relationships and found a higher potency of lower doses [64]. In an in vitro study investigating the effect of Aronia melanocarpa supplementation on reactive oxygen species-induced neuronal cell death, the low dose exerted a protective effect, while high dose supplementation promoted superoxide-induced cell death [65]. ...
Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on cognition in older adults and children. However, the effect of anthocyanin-rich Aronia melanocarpa extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = −3.37; p = 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44; p = 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline.
... It might be expected that a higher dose of quercetin would affect more both the oxidant damage and the antioxidant capacity. However, in the study of Kay et al. 33 it was clearly shown that dose-response curves of flavonoids could be non-linear. Therefore, for using flavonoids as complementary treatment, more detailed studies on dose-response curves are needed. ...
Purpose
To examine the effects of quercetin on healing of experimental colon anastomosis injury in early and late period.
Methods
Eighty male Wistar-Albino rats were divided into 8 groups. For all groups, left colons of the rats were resected and for the rest end-to-end anastomosis was performed. Two of the groups for which the experiment protocol was ended on the 3rd and 7th day following the anastomosis were not administered with either quercetin or dimethylsulfoxide DMSO, whereas two other groups were administered with DMSO only, and four other groups were administered with quercetin dissolved in DMSO in doses of 20 and 100 mg/kg during the protocol. At the end of the study, anastomosis line was resected, histopathological evaluation was performed and bursting pressure, malondialdehyde, superoxide dismutase, catalase, and hydroxyproline levels were measured.
Results
Quercetin significantly increased hydroxyproline, superoxide dismutase, catalase levels, histopathological healing score, bursting pressure values and decreased malondialdehyde level in early period. It also significantly increased superoxide dismutase, catalase, and hydroxyproline levels and decreased malondialdehyde level in late period.
Conclusion
It was seen that quercetin speeds up the injury healing process and reveals an antioxidant effect, specifically in early period.
... Whilst this may simply be due to the margin of error in measuring human cognitive function, it is also worth noting that U-shaped dose responses (i.e., effects at low and high, but not interim doses) are commonly observed in biological systems [47]. Inverse, nonlinear, bimodal and U-shaped dose responses have also been described in animals and humans following diverse phytochemicals [22,26,48,49], including Avena sativa extracts [33,34]. The same has been seen with regards potential modulatory mechanisms. ...
Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may improve mood or protect against stress, for instance species-specific triterpene saponins, to date this possibility has not been examined. The current study investigated the effects of a single dose and four weeks of administration of a novel, Avena sativa herbal extract (cognitaven®) on cognitive function and mood, and changes in psychological state during a laboratory stressor. The study adopted a dose-ranging, double-blind, randomised, parallel groups design in which 132 healthy males and females (35 to 65 years) received either 430 mg, 860 mg, 1290 mg green oat extract or placebo for 29 days. Assessments of cognitive function, mood and changes in psychological state during a laboratory stressor (Observed Multitasking Stressor) were undertaken pre-dose and at 2 h and 4 h post-dose on the first (Day 1) and last days (Day 29) of supplementation. The results showed that both a single dose of 1290 mg and, to a greater extent, supplementation for four weeks with both 430 mg and 1290 mg green oat extract resulted in significantly improved performance on a computerised version of the Corsi Blocks working memory task and a multitasking task (verbal serial subtractions and computerised tracking) in comparison to placebo. After four weeks, the highest dose also decreased the physiological response to the stressor in terms of electrodermal activity. There were no treatment-related effects on mood. These results confirm the acute cognitive effects of Avena sativa extracts and are the first to demonstrate that chronic supplementation can benefit cognitive function and modulate the physiological response to a stressor.
... The increase in FMD following BOJ intake can be considered as relatively large, given that the chronic effect of flavonoids on FMD is only 0.73% (range: 0.17-1.30%), as demonstrated by a pooled analysis of flavonoid intervention trials (42). The effects of BOJ on FMD in the current study are comparable to those of cocoa powder (800 mg cocoa flavonoids/d for 1 wk) consumed by healthy individuals (43). ...
Background:
Epidemiological studies have indicated an inverse association between citrus fruit consumption and cardiovascular disease (CVD) risk. There is, however, a paucity of data concerning effects of blood orange juice (BOJ) intake on endothelial function and cardiovascular risk biomarkers.
Objectives:
We examined short-term effects of BOJ on endothelial function, blood pressure, lipid profile, and inflammatory markers in healthy participants of European origin who were overweight or obese.
Methods:
In a randomized, controlled, single-blind, crossover trial, 15 men and women (age: 28.7 ± 6.5 y; BMI: 28.3 ± 3.1 kg/m2) consumed BOJ or a sugar-matched control drink (CD) (200 mL twice daily) for 2 wk with a washout period of 1 wk. Endothelial function, measured as flow-mediated dilation (FMD) (primary outcome), and the secondary outcomes blood pressure, anthropometric measures, lipid profile, inflammatory markers, markers of vasodilation and vasoconstriction, and urinary flavanone metabolites were evaluated prior to and at the end of each treatment period following an overnight fast. Changes between treatments over time were assessed using repeated-measures ANOVA.
Results:
The results demonstrate a significant increase in FMD following BOJ consumption (pre: 8.15% ± 2.92%; post: 10.2% ± 3.31%; P = 0.002) compared with CD (pre: 8.11% ± 2.52%; post: 7.77% ± 2.43%; time × treatment interaction: P = 0.001). Concurrent significant increases in urinary hesperetin-3'-glucuronide and hesperetin-7-glucuronide were observed following BOJ supplementation only (time × treatment interaction: P ≤ 0.01). Baseline blood pressure, lipid profile, high-sensitivity C-reactive protein, and endothelin-1 were generally within healthy ranges and unaffected by the intervention.
Conclusions:
A 2-wk consumption of BOJ exerted favorable effects on endothelial function in healthy women and men who were overweight or obese, which is likely mediated by the combined actions of anthocyanin and flavanone metabolites on mechanisms that contribute to enhancing NO bioavailability. This trial was registered at clinicaltrials.gov as NCT03611114.
... Some of the most often reported positive effects of hesperidin are anti-inflammatory, antiallergenic, antiviral and anticarcinogenic effect [2]. Hesperidin contributes to strength of the blood vessels walls, leads to the bruise preventing and some conditions related to certain vascular disorders [3]. Further, even promising effects of orange juice daily consumption have been reported as the results of performed studies, such as lowering of diastolic blood pressure [4]. ...
Hesperidin is the flavonoid heteroside most found in citrus species, such as grapefruit, lemon and orange. It is applied in the treatment of numerous cardiovascular diseases, with many products containing hesperidin in combination with other flavonoid heterosides or vitamin C. The aim of this study was to develop and validate a simple, rapid and sensitive and low-cost method for determination of hesperidin in tablets and orange juices. The developed spectrophotometric method is based on the formation of the Zn(II)-hesperidin complex in 70 v/v% methanol at pH 3.12, with max of absorption at λmax= 283 nm. The method of variation of equimolar solutions confirmed the stoichiometry of the complex as hesperidin: zinc= 2:1. The stability constant of the complex was obtained by the Bjerrum method and it is logβ2 = 17.01 at pH 3.12. Linearity range for the developed method was defined as 0.61-7.32 μg/mL, (confirmed by coefficient of determination, r2 = 0.9882), while limits of detection and quantification were calculated as LOD = 0.15 μg/mL and LOQ = 0.45 μg/mL. Fairly high precision of the method is indicated by low values of CV, varying in the range 0.26-1.23%. The proposed method fulfills all aimed requirements, and it was successfully applied for determination of hesperidin in tablets with recovery value 92.2 % and commercially available orange juices.
... These components may be present in the root, stems, leaves, flowers, fruits, seeds, seed coat, fruit coat, and bark etc. separately or in combined form. We will concentrated to find out and isolate the potent bioactive compound present in this plant for further study to treat fatal diseases [3][4][5][6]. From a qualitative and quantitative point of view, the phytochemicals may vary from one part to others even in the same plant. Not only differ in their distribution but also lack of knowledge in their seasonal occurrence throughout the year [7]. ...
Background: There is much investigation with the Andrographis paniculata which is a very well-known medicinal plant, people were using this plant from ancient years, but this another species Andrographis echioides was not explored too much for many years. In this study we tried to find out the important phyto constitiuents, antibacterial activity and anti-inflammatory activity of this plant. Aim: The main aim of the present study, was to screen phytochemical derivatives from an Indian medicinal plant Andrographis echioides (L) Nees and to evaluate the antibacterial potential, and anti-inflammatory activity also. Study Design: Various tests or experiment was done in this study according to the review of the literature with little modification, a preliminary phytochemical screening was carried out in the plant extracts using qualitative methods. The whole plant of Anrographis echioides was subjected to soxhlet extraction using organic solvent of methanol, acetone, and petroleum ether. The antibacterial activity of acetone, methanol and petroleum ether whole plant extracts of Andrographis echioides was carried out using agar well diffusion method, anti-inflammatory activity was checked using fresh egg albumin method, and a statistical analysis was done using SPSS to prove that there is a strong correlation between the activity of our plant sample and a standard commercial drug (NASID). Place and Duration of the Study: The whole study was done in Panskura Banamali College, Vidyasagar University, Department of Biotechnology sponsored by BOOST, Louis Pasteur laboratory, West Bengal, India. The study was done between 17th August 2018 - 30th February 2019. Results: All these tests were done triplicate and the mean value was taken. The phytochemical analysis reveals that the plant has some important phytoconstituents such as Tannins, flavonoids, phenolic compounds, glycosides and terpenoids. The Acetone and Methanol extracts are showed the best zone of inhibition against the severe pathogens such as S. aureus (A.E-33 mm, M.E-28 mm), S. typhi (A.E- 26.67 mm, M.E-28.33 mm). The methanolic extract of Andrographis echioides showed excellent anti-inflammatory activity comparing to the NASID (Non-steroidal anti-inflammatory drugs) Diclofenac sodium, it showed almost same activity. Conclusion: Experimental findings reveal Andrographis echioides is the best herbal to control specially S. typhi, E. coli, S. aureus, K. pneumoniae. The phytochemical constituents which are responsible for many pharmacological activities, may be useful for the evolution of pharmaceutical and for the therapy of ailments, and also can used as a an potent anti-inflammatory natural remedy without any side effect.
... In the arid and semiarid zones plants produce various types of secondary metabolites which are helpful for their existence 2 . Flavonoids should have great antioxidant properties and can play versatile protective role against oxidative stress [3][4][5][6][7][8] vegetables, flowers, fruits, stems, root and leaves 10 . According to online food database "Phenol-Explorer" different onions, tea, grape fruits, red-wine, citrus fruits, cocoa beans are the chief source of flavonoids [11][12][13] . ...
... Kay and co-workers indicated that anthocyanins underwent extensive first-pass metabolism before entering the systemic circulation as metabolites. Therefore, the low concentration of anthocyanins in the blood was in great contrast to their high concentration in the intestinal tissues (Kay, Hooper, Kroon, Rimm, & Cassidy, 2012;Mallery et al., 2011). However, the study by Manach revealed that the low bioavailability of anthocyanins was caused by limited intestinal absorption, high rates of cellular uptake, metabolism and excretion (Manach, Williamson, Morand, Scalbert, & Remesy, 2005). ...
Influenza is a highly dangerous disease, as it is connected with a risk of complications and in extreme cases – also death. Treatment based on virustatic drugs is not always effective, as mutations lead to the development of drug-resistant viruses. A relatively efficacious protection against influenza is provided by vaccinations; however, they are not very popular due to the common distrust in their efficacy and concerns over their supposed adverse effects. Phytotherapy uses several raw materials which may be applied in the prevention and treatment of influenza. Plant origin materials of particular interest include berry fruits containing considerable amounts of bioactive compounds. The multifaceted health-promoting action of berry fruits is connected first of all with the presence of polyphenols. Antiviral activity against influenza viruses results from the presence of anthocyanins and other classes of flavonoids, proanthocyanidins and phenolic acids. An important group of compounds other than polyphenols, which may be readily used in influenza infections comprises polysaccharides. Research indicates that components of berry fruits may inhibit replication of the virus both directly and indirectly, e.g. by blocking surface glycoproteins of influenza virus and stimulating the immune system of the organism. In consequence to their properties berry fruits are raw materials of potential use in the prevention and treatment of influenza.
... In the arid and semiarid zones plants produce various types of secondary metabolites which are helpful for their existence 2 . Flavonoids should have great antioxidant properties and can play versatile protective role against oxidative stress [3][4][5][6][7][8] vegetables, flowers, fruits, stems, root and leaves 10 . According to online food database "Phenol-Explorer" different onions, tea, grape fruits, red-wine, citrus fruits, cocoa beans are the chief source of flavonoids [11][12][13] . ...
Hellenia speciosa an important herbal to the tribal, not founded as vivid day up till now. Except few fragmentary findings no investigation in respect to phytochemical screening. And antibacterial activity of the present day have not been done keeping this point in mind phytochemical screening and anti-bacterial activity recently done against four bacteria (E. coli, S.typhi, S. aureus, K.pneumoniae) using Acetone, Methanol, Petroleum Ether as organic solvent. Flavonoids as marker of phytochemicals identified for best results where Methanol extracts for S.typhi and Acetone extract for S.aureus showed excellent results rather than extract in Petroleum Ether.
... Метаанализ 22 рандомизированных контролируемых исследований показал, что регулярное употребление антоцианозидов в течение 2-12 недель оказывает влияние на функции сердечно-сосудистой системы, способствует уменьшению индекса массы тела (p < 0,0001), снижению уровня липопротеинов низкой плотности (p = 0,003), глюкозы (p = 0,004) и гликированного гемоглобина (p = 0,04), причем как у здоровых лиц, так и в группе риска сердечно-сосудистых заболеваний [8]. С помощью неинвазивного ультразвукового метода определения потоко-опосредованной вазодилатации, который признан «золотым стандартом» для оценки эндотелиальной функции, рядом авторов был продемонстрирован положительный эффект антоцианозидов на сосудистую реактивность магистральных артерий [9,10]. Под влиянием антоцианозидов происходит активация эндотелиальной NO синтазы -фермента, который участвует в образовании мощного эндогенного вазодилататора -оксида азота [11]. ...
The literature review presents information on positive effects of anthocyanins on functional indices of cardiovascular system, vascular reactivity of main arteries, microcirculation and retrobulbar blood flow. The positive effect of anthocyanins on the reactivity of main arteries was detected using non-invasive ultrasound method for assessment of flow-mediated dilation andendothelial function. Numerous randomised-controlled trials showed the effectiveness of the long-term supplementation with anthocyanins (during 6–24 months) in correction of microcirculation impairment and functional indices of visual system. The increase of plasma endothelin-1 (ET-1) level and the pathological vascular reactivity have been noted in ocular ischemic diseases such as diabetic retinopathy, occlusion of retinal veins and arteries. We registered the normalization of the plasma ET-1 level, significant improvement of blood flow in neuroretinal rim area and peripapillary area of retina without changes in mean indices of intraocular pressure and ocular perfusion pressure in patients with open-angle glaucoma after anthocyanins administration. There was no progression of visual fields defects. The resulting effect of anthocyanins supplementation consists of metabolic regulation of blood flow and flow-dependent vasodilatation due to the influence on vascular endothelium.Anthocyanins also increase the expression of endothelial nitric oxide (NO) synthase, an enzyme that generates powerful endogenous vasodilator NO. Anthocyanins regulate a number of complex immune and inflammatory signaling pathways involved in maintaining vascular functional activity. Positive dynamic of blood flow velocities and normalization of resistance indices in ocular vessels were detected in patients with dry age-related macular degeneration after 2 months anthocyanins supplementation. That indicates the improvement of ocular blood flow circulation and favorable prognosis for retinal dystrophies. The instrumental examination of blood flow in different vascular systems including microcirculation and main arteries are very useful for assessment of the effectiveness of anthocyanin supplementation.
... The authors showed that each 1% increase in FMD was associated with a relative risk of cardiovascular events of 0.87 (95% CI: 0.83, 0.91); the 1.14% chronic improvement in FMD would have important consequences for CVD risk and in combination with the small, but robust, improvements in HDL cholesterol, blood pressure, and HOMA-IR may be substantial. Our RCT results concur with 2 previous meta-analyses that only evaluated a limited number of foods and reported beneficial effects on outcomes including HDL cholesterol, blood pressure, HOMA-IR, and FMD (7,50). Similar to their review, we did not find a linear relation between flavan-3-ol intake and outcomes of interest. ...
Background:
Although available data suggest that some dietary flavan-3-ol sources reduce cardiometabolic risk, to our knowledge no review has systematically synthesized their specific contribution.
Objective:
We aimed to examine, for the first time, if there is consistent evidence that higher flavan-3-ol intake, irrespective of dietary source, reduces cardiometabolic risk.
Methods:
MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched for prospective cohorts and randomized controlled trials (RCTs) published from 1946 to March 2019 on flavan-3-ol intake and cardiovascular disease (CVD) risk. Random-effects models meta-analysis was used. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach assessed the strength of evidence.
Results:
Of 15 prospective cohorts (23 publications), 4 found highest compared with lowest habitual intakes of flavan-3-ols were associated with a 13% reduction in risk of CVD mortality and 2 found a 19% reduction in risk of chronic heart disease (CHD) incidence. Highest compared with lowest habitual intakes of monomers were associated with a reduction in risk of type 2 diabetes mellitus (T2DM) (n = 5) and stroke (n = 4) (10% and 18%, respectively). No association was found for hypertension. Of 156 RCTs, flavan-3-ol intervention resulted in significant improvements in acute/chronic flow-mediated dilation (FMD), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), LDL and HDL cholesterol, triglycerides (TGs), hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). All analyses, except HbA1c, were associated with moderate/high heterogeneity. When analyses were limited to good methodological quality studies, improvements in TC, HDL cholesterol, SBP, DBP, HOMA-IR, and acute/chronic FMD remained significant. In GRADE evaluations, there was moderate evidence in cohort studies that flavan-3-ol and monomer intakes were associated with reduced risk of CVD mortality, CHD, stroke, and T2DM, whereas RCTs reported improved TC, HDL cholesterol, SBP, and HOMA-IR.
Conclusions:
Available evidence supports a beneficial effect of flavan-3-ol intake on cardiometabolic outcomes, but there was considerable heterogeneity in the meta-analysis. Future research should focus on an integrated intake/biomarker approach in cohorts and high-quality dose-response RCTs. This review was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42018035782.
... Different flavonoids show different modes of action, e.g., luteolin enhances the production of acetylcholine-induced NO, while buddleoside suppresses acetylcholinesterase activity [122]. A systematic review of randomized controlled trials [123] analyzed the impact of flavonoids on vascular function, specifically flow-mediated dilation (FMD) and blood pressure. In pooled analysis of all flavonoid interventions, FMD improved both acutely and chronically and this effect was more pronounced for several flavonoid subclass constituents. ...
Cardiovascular diseases (CVD) are complex entities with heterogenous pathophysiologic mechanisms and increased oxidative stress has been viewed as one of the potential common etiologies. A fine balance between the presence of reactive oxygen species (ROS) and antioxidants is essential for the proper normal functioning of the cell. A basal concentration of ROS is indispensable for the manifestation of cellular functions, whereas excessive levels of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, eventually leading to necrosis and apoptotic cell death. CVD is the main cause of death worldwide with several conditions being affected by oxidative stress. Increased ROS lead to decreased nitric oxide availability and vasoconstriction, promoting arterial hypertension. ROS also negatively influence myocardial calcium handling, causing arrhythmia, and augment cardiac remodeling by inducing hypertrophic signaling and apoptosis. Finally, ROS have also been shown to promote atherosclerotic plaque formation. This review aims at giving an introduction into oxidative stress in CVD, with special focus on endothelial dysfunction, and then examining in detail the role of oxidative stress in the most prevalent of these diseases. Finally, potential nutraceuticals and diets that might be beneficial in diminishing the burden of oxidative stress in CVD are presented.
... In some cases, the markers of vascular function that were measured showed inconsistent effects. [46][47][48] This could be due to the inclusion of studies with heterogeneous characteristics or a high risk of bias. Moreover, most of the studies focused on bioactive compounds and bioactive-rich foods in general, making the specific effects of berries very difficult to identify. ...
Context:
Berries are a source of polyphenols with recognized health-promoting activities. Several studies suggest that consumption of berries may improve vascular function.
Objective:
The aim of this systematic review is to provide evidence of short- and long-term benefits of berries on outcomes of vascular function.
Data sources:
Human intervention studies were collected from PubMed and Scopus databases.
Study selection:
Studies were eligible if they investigated the effects of acute or chronic berry consumption on one or more markers of vascular function in humans and provided a characterization of the berry polyphenolic content. Only randomized controlled trials were included, and studies were excluded if berries were combined with other foods.
Data extraction:
After selection, 22 randomized controlled trials were included and analyzed, most of which were performed in healthy individuals or patients with cardiovascular risk factors.
Results:
The overall results seem to suggest a protective role of berries in vascular function, likely dependent on the time of exposure, the type and dose of berry, and the biomarkers analyzed. Flow-mediated dilation and reactive hyperemia index (markers of vascular reactivity) improved following short-term interventions, while pulse wave velocity and augmentation index (markers of arterial stiffness) improved only after medium- to long-term intervention.
Conclusions:
Current evidence suggests that berries, at physiological relevant doses, may have a role in the modulation of vascular function and stiffness. High-quality human intervention trials are encouraged in order to strengthen these findings and to better elucidate the mechanisms involved in such modulation.
The present thesis reports on 4 studies on soccer-specific skill performance in academy male soccer players and novel nutritional strategies that could be used in order to help maintain skill. The first study reported in this thesis investigated how the consumption of 250 mL of a 12% carbohydrate-electrolyte beverage, both before the start of a 90-min soccer match simulation and at half time, influenced the preservation of soccer-specific abilities (specifically, dribbling, and passing proficiency), sprinting speed, and anaerobic endurance running capacity. The main finding from this study was that higher passing scores were consistently attained by players using both their dominant and non-dominant feet from the 60-min mark onward in the match simulation when ingesting the carbohydrate-electrolyte beverage. Notably, this sustained skill performance was achieved without a decline in passing speed. Interestingly, passing speed was better maintained particularly on the non-dominant foot when the players consumed the 60g of carbohydrates. Concomitantly, high-intensity running capacity was improved when the participants ingested the 12% carbohydrate-electrolyte solution compared with placebo; all of these positive findings occurred with minimal impact on gut comfort. In the second study, the test-rest reliability of soccer-specific skills was assessed using a modified version of the Russell et al (2011) soccer match simulation protocol. The results suggested that the modified soccer match simulation protocol exhibited promising reliability for most of the evaluated skills. Good to excellent reliability was reported for passing speed and accuracy and sprint speed. However, dribbling and shooting variables showed lower reliability. Additionally, it was determined that the modified version of the protocol could be easily incorporated into professional club settings without the need for specialised equipment. The third study identified that a single dose of a beverage containing 300 mg of coffeeberry ingested one hour before a soccer-specific skill assessment, conducted under rested conditions, did not result in any significant alteration in soccer skill performance compared with placebo. Moreover, it was concluded that it would be prudent to explore similar studies involving activities that induce physical and/or mental fatigue to better understand how coffeeberry might mitigate the negative impact of fatigue on soccer-specific skill performance. In the fourth and final study, the primary aim was to examine the impact of a single pre-exercise dose of a beverage containing 300 mg of coffeeberry on soccer skill performance throughout a 45-min period of simulated soccer-match play and on soccer skills evaluated after exercise-induced fatigue. The study confirmed that the consumption of coffeeberry extract could be advantageous in preserving some aspects of soccer-specific skill performance under exercise conditions. Specifically, it demonstrated notable maintenance of passing performance with retention of passing speed and accuracy during a 45-min simulated soccer match.
Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential.
Plants are the primary repository of the vast majority of meals, medications, and nutritional supplements. Primary and secondary metabolites are the two types of plant compounds known as phytochemicals. Primary metabolites are essential for plant survival since they are involved in tasks such as cell division, growth, reproduction, respiration, metabolism, and storage. Secondary metabolites are more than just plant byproducts from main metabolism; they have far-reaching implications for plant defense systems, ecology, and evolution. These molecules created by organisms do not aid in their growth and development, but they are important in plenty of other ways, such as a cofactor, in defense, and in other catalytic functions. Products of glycolysis, the TCA cycle, or the shikimate pathway are frequently used as precursors for the synthesis of the tens of thousands of secondary metabolites that have previously been characterized. In comparison to variances in main metabolism reactions, which are generally conserved, secondary metabolism pathways exhibit far greater variability at the species, organ, tissue, and cell levels, as well as at different developmental phases. Additionally, secondary metabolism's high level of catalytic promiscuity, which is most likely because of its recent deviation from primary metabolism and the weaker selection pressure applied to secondary metabolic enzymes compared to primary metabolic enzymes, is another component that is assumedly necessary for the great variety of secondary metabolism. A variety of metabolic routes are used to create secondary metabolites, including the MEP (Methylerythritol-23 phosphate pathway) for phenolic compounds and the shikimic acid system for aromatic and nitrogen-containing compounds. A key pathway other than these is the malonic pathway, which connects glycolysis to the precursor acetyl CoA.
Adequate intake of fruits has been linked with the reduction in the risk of chronic diseases and maintenance of body weight. Fruits and Their Roles in Nutraceuticals and Functional Foods covers recent research related to the bioactive compounds present in a variety of fruits
In recent years, many efforts have been made to identify micronutrients or nutritional strategies capable of preventing, or at least, attenuating, exercise-induced muscle damage and oxidative stress, and improving athlete performance. The reason is that most exercises induce various changes in mitochondria and cellular cytosol that lead to the generation of reactive species and free radicals whose accumulation can be harmful to human health. Among them, supplementation with phenolic compounds seems to be a promising approach since their chemical structure, composed of catechol, pyrogallol, and methoxy groups, gives them remarkable health-promoting properties, such as the ability to suppress inflammatory processes, counteract oxidative damage, boost the immune system, and thus, reduce muscle soreness and accelerate recovery. Phenolic compounds have also already been shown to be effective in improving temporal performance and reducing psychological stress and fatigue. Therefore, the aim of this review is to summarize and discuss the current knowledge on the effects of dietary phenolics on physical performance and recovery in athletes and sports practitioners. Overall, the reports show that phenolics exert important benefits on exercise-induced muscle damage as well as play a biological/physiological role in improving physical performance.
Dietary nitrate (NO3-) supplementation can reduce the oxygen cost of submaximal exercise, but this has not been reported consistently. We hypothesised that the number of step transitions to moderate-intensity exercise, and corresponding effects on the signal-to-noise ratio for pulmonary V˙ O2, may be important in this regard. Twelve recreationally active participants were assigned in a randomised, double-blind, crossover design to supplement for 4 days in three conditions: 1) control (CON; water); 2); PL (NO3--depleted beetroot juice); and 3) BR (NO3--rich beetroot juice). On days 3 and 4, participants completed two 6-min step transitions to moderate-intensity cycle exercise. Breath-by-breath V˙ O2 data were collected and V˙ O2 kinetic responses were determined for a single transition and when the responses to 2, 3 and 4 transitions were ensemble-averaged. Steady-state V˙ O2 was not different between PL and BR when the V˙ O2 response to one-, two- or three-step transition was compared but was significantly lower in BR compared to PL when four-step transitions was considered (PL: 1.33 ± 0.34 vs. BR: 1.31 ± 0.34 L·min-1, P < 0.05). There were no differences in pulmonary V˙ O2 responses between CON and PL (P > 0.05). Multiple step transitions may be required to detect the influence of NO3- supplementation on steady-state V˙ O2.
Type 2 diabetes mellitus (T2DM) represents 90 – 95 % of all diabetes cases and is characterized by β-cell dysfunction and insulin resistance leading to hyperglycemia. Hyperglycemia increases oxidative stress, inflammation, and orthosympatic activity and limits bioavailability of nitric oxide (NO), resulting in micro- (nephropathy, neuropathy, retinopathy) and macrovascular (cerebrovascular, cardiovascular, and peripheral artery disease) complications. These complications result in higher morbidity and mortality rates, decrease quality of life, and increase health economic burden. Increasing physical activity and a more balanced, healthy food intake are the first-line management. Herein, the promising vascular health benefits of nutraceuticals, like flavonoids and more specifically flavanols, have gained interest.Flavanols are natural substances present in several fruits, teas, red wines, beans, and predominantly in cocoa and are believed to beneficially affect human health. Based on epidemiological, in vitro-, animal-, and human studies, cocoa flavanols (CF) would have antioxidant properties, improve endothelial function, lower blood pressure (BP), and reduce inflammation. The mechanisms of action of CF are not yet completely understood, but it is believed that increasing NO bioavailability and –activity and antioxidative actions like inhibiting lipid peroxidation and nicotinamide adenine dinucleotide phosphate oxidase and scavenging free radicals play a key role.So far, research into the potential beneficial vascular health properties of CF in patients with diabetes mellitus (DM) is limited and demonstrated inconsistent results. However, based on the pathophysiology of diabetic vascular complications and the believed mechanisms of action of CF, one could assume that CF would exert vascular protection in T2DM subjects. Therefore, this doctoral research investigated whether CF exert vascular health benefits in patients with T2DM through the following 3 aims: (1) examine the evidence for CF-induced vascular health properties in patients with DM, (2) setup of a robust, standardized, clearly described trial protocol, and (3) investigate the acute effects of CF on peripheral vascular reactivity in patients with T2DM via execution of the described acute, randomized, double-blinded, placebo-controlled cross-over trial.First, we published a systematic review and meta-analysis on the vascular health effects of CF in patients with DM. We highlighted the need for more, robust, standardized research because of the high heterogeneity in administered intervention (dose, duration and frequency, nature of intervention), the studied population (age, sex, BMI, medical therapy, stage of disease), and measurement methods. Because of paucity of reports, we could only perform the meta-analysis on the mid/long-term effects of CF on blood pressure (BP) in patients with DM and mixed populations with increased cardiovascular risk. This meta-analysis indicated weak evidence for a reduction in diastolic BP (DBP) of, at best, 1 – 2 mmHg. No effect on systolic BP (SBP) was detected. Furthermore, CF effects on BP would be stronger in female, hypertensive, younger adults, providing a CF dose comprising at least 90 mg epicatechine (EC), and when ingested in 1 daily batch.Second, the protocol paper illustrating our setup acute, randomized, double-blinded, placebo-controlled cross-over trial was published. Here we thoroughly described our protocol trial in which we take into account the limitations in previous studies. We believe that acute studies in which subjects ingest a pure cocoa extract are the first step to gain insight in CF actions as possible confounding impact of additional fat, sugars, milk or other substances could mask/ counteract/ strengthen the effects of CF [...]
Recent epidemiological and intervention studies have suggested that polyphenol-rich plant food consumption reduced the risk of cognitive decline. However, the findings were tentative and by no means definitive. In the present study, we examined the impact of short-term oral administration of cinnamtannin A2 (A2), an (−)-epicatechin tetramer, on adult hippocampal neurogenesis and cognitive function in mice. Mice received supplementation with vehicle (20% glycerol) or 100 μg/kg A2 for 10 days. Then, we conducted the open field test, the object location test, and the novel object test. In the open field test, the A2-treated group tended to spend more time in the center of the arena, compared to the vehicle-treated group. The A2-treated group spent significantly more time exploring objects placed in different locations, compared to the vehicle-treated group. There were no significant differences between groups in the object preference index or in the novel object test. In addition, A2 administration significantly increased the number of hippocampal bromodeoxyuridine-labeled cells in the dentate gyrus, but not in the CA1 or CA3 regions. These results suggested that short-term administration of A2 may impact spatial memory by enhancing neurogenesis in the dentate gyrus of adult mice.
The term "flavonoid" is a broad term given to the collection of natural polyphenolic compounds which occur in plants (fruits, vegetables, roots, flowers, stems, bark, leaves) as their secondary metabolites. Subsequent research reveals that flavonoids possess anti-inflammatory, anti-mutagenic, anti-oxidative, anti-ageing, and anti-carcinogenic effects along with their capacity to modulate enzymatic activities, inhibit cell proliferation, and inhibit bacterial growth, among others. The main shortcomings of oral administration of flavonoids as therapeutic that various studies have revealed are related to their stability, bioefficacy, and bioavailability. Novel nanotechnological strategies involving nanocarrier systems are proving promising to overcome the delivery challenge of flavonoids as therapeutics. Nanocapsules, nanospheres, solid lipid nanoparticles, nanoemulsions, micelles are examples of novel nanocarrier systems that are currently being explored for targeted and efficient bio functioning of flavonoids after their oral administration.
Scope
A main risk factor of atherosclerosis is a Western diet (WD) rich in n‐6 PUFA sensitive to oxidation. Their oxidation can be initiated by heme iron of red meat leading to the formation of 4‐hydroxy‐2‐nonenal (4‐HNE), a cytotoxic aldehyde. An increased 4‐HNE production is implicated in endothelial dysfunction and atherosclerosis. By contrast, a diet rich in proanthocyanidins reduces oxidative stress and arterial diseases. This study evaluates the effects of a WD on vascular integrity in ApoE−/− mice and the protective capacity of apple extract and puree rich in antioxidant proanthocyanidins.
Methods and results
ApoE‐/‐ mice were fed during 12 weeks with a WD with or without n‐6 PUFA. Moreover, two WD + n‐6 PUFA groups were supplemented with apple puree or phenolic extract. We report an increase in digestive 4‐HNE production associated with a rise in plasmatic 4‐HNE and oxLDL concentrations. Oxidizable n‐6 PUFA consumption was associated with a worsened endothelial dysfunction and atherosclerosis. Interestingly, supplementations with apple polyphenol extract or puree prevented these impairments while reducing oxidative stress.
Conclusion
n‐6 lipid oxidation during digestion may be a key factor of vascular impairments. Nevertheless, an antioxidant strategy could limit 4‐HNE formation during digestion and thus durably protect vascular function.
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Selon l’OMS, d’ici 2030, près de 23,6 millions de personnes décèderont de maladies cardiovasculaires chaque année représentant la première cause de mortalité ainsi qu’un enjeu majeur de santé publique. Parmi celles-ci, les pathologies ischémiques sont les plus fréquentes. Elles ont pour origine une dysfonction endothéliale favorisant le développement de l’athérosclérose. Le principal facteur de risque associé à ces pathologies est un régime de type occidental riche en acides gras polyinsaturés n-6, sensibles à l’oxydation, et en fer héminique apporté par la viande rouge. A l’opposé, une alimentation riche en fruits, légumes et céréales peut être source d’antioxydants naturels comme les polyphénols. Parmi les polyphénols, les procyanidines (PCs, flavonoïdes) apparaissent comme corrélés à une réduction des maladies coronariennes et des accidents vasculaires cérébraux. Ainsi, les objectifs de ce travail de thèse étaient : 1) d’évaluer la formation de produits d’oxydation lipidique dans le tractus gastro-intestinal au cours de la digestion puis leur effet chronique après absorption intestinale sur la fonction vasculaire ; 2) d’évaluer l’influence d’une supplémentation alimentaire en PCs de pomme comme stratégie antioxydante primaire afin de prévenir la formation de produits d’oxydation lipidique et d’ainsi préserver la fonction vasculaire. Des premiers résultats ont été acquis dans un système constitué par une émulsion huile de tournesol-dans-eau et du fer héminique (métmyoglobine) et dans des conditions simulant les phases initiale et médiane de digestion à pH 5 et 3, respectivement. Il apparait que l’oxydation lipidique, évaluée à travers la formation des diènes conjugués lipidiques (DC) et du 4-hydroxynonénal (4-HNE), est amorcée plus rapidement à pH 3 qu’à pH 5, que la pepsine accélère l’accumulation des DC à pH 5 par la formation d’une forme de micro-métmyoglobine plus accessible aux acides gras. Les trois matrices (pomme fraiche, purée et extrait phénolique) ajoutées à dose nutritionnelle montrent une capacité inhibitrice plus faible à pH 5 en présence de pepsine alors que celle-ci semble augmentée à pH 3. Cette stratégie antioxydante a ensuite été évaluée en modèle in vitro de digestion gastro-intestinale démontrant une réduction de 73-96% de la formation du 4-HNE en fin de phase gastrique et de 60-95% en fin de phase intestinale. Enfin, une étude chronique a été conduite pour évaluer in vivo l’impact de l’oxydation lipidique dans un modèle de souris ApoE-/-. L’oxydation des lipides lors de la digestion était associée à une augmentation du taux plasmatique de LDLox et du stress oxydant ayant pour conséquence une altération de la fonction endothéliale. Cette altération de l’endothélium était associée à une augmentation du développement des plaques d’athérome potentiellement instables. De manière intéressante, la supplémentation en polyphénols (purée ou extrait phénolique) prévenait l’augmentation du taux de LDLox, l’exacerbation des altérations endothéliales ainsi que la taille de la plaque d’athérome. En conclusion, les polyphénols de pomme limiteraient la formation de 4-HNE absorbable au cours de la digestion protégeant à long terme la fonction vasculaire. Nos résultats sont en faveur d’une réintroduction de fruits riches en PCs (pomme, poire) dans une alimentation de type occidental.
In this study, the antioxidant activity of germinating Chinese wild rice was found to decline initially, after which it increased. The largest difference in antioxidant activity was observed between the 36-h (G36) and the 120-h germination (G120) stage. We further assessed the dynamic changes in metabolites, phenolic acids, flavonoids, and phenolic biosynthetic genes in germinating Chinese wild rice. Ultra-high performance liquid chromatography–triple quadrupole mass spectrometry revealed that 315 metabolites were up-regulated and 28 were down-regulated between G36 and G120. Levels of p-hydroxybenzoic acid, p-hydroxybenzaldehyde, vanillin, p-coumaric acid, ferulic acid, and epigallocatechin increased significantly during germination. Gene expression of four phenylalanine ammonia-lyases, one 4-coumarate-CoA ligase, one cinnamoyl-CoA reductase, two cinnamyl alcohol dehydrogenases, one chalcone synthase, and one chalcone isomerase was significantly higher at G120 than at G36 and promoted phenolics accumulation. This study elucidated the biochemical mechanisms involved in antioxidant activity and phenolic profile changes during Chinese wild rice germination.
There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD).
The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors.
We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses.
We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies.
We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.
Flavonoids are plant-based phytochemicals with cardiovascular protective properties. Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease mortality.
We examined the association between flavonoid intake and cardiovascular disease (CVD) mortality among participants in a large, prospective US cohort.
In 1999, a total of 38,180 men and 60,289 women in the Cancer Prevention Study II Nutrition Cohort with a mean age of 70 and 69 y, respectively, completed questionnaires on medical history and lifestyle behaviors, including a 152-item food-frequency questionnaire. Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard RRs and 95% CIs for associations between total flavonoids, 7 flavonoid classes, and CVD mortality.
During 7 y of follow-up, 1589 CVD deaths in men and 1182 CVD deaths in women occurred. Men and women with total flavonoid intakes in the top (compared with the bottom) quintile had a lower risk of fatal CVD (RR: 0.82; 95% CI: 0.73, 0.92; P-trend = 0.01). Five flavonoid classes-anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins-were individually associated with lower risk of fatal CVD (all P-trend < 0.05). In men, total flavonoid intakes were more strongly associated with stroke mortality (RR: 0.63; 95% CI: 0.44, 0.89; P-trend = 0.04) than with ischemic heart disease (RR: 0.90; 95% CI: 0.72, 1.13). Many associations appeared to be nonlinear, with lower risk at intakes above the referent category.
Flavonoid consumption was associated with lower risk of death from CVD. Most inverse associations appeared with intermediate intakes, suggesting that even relatively small amounts of flavonoid-rich foods may be beneficial.
Dietary flavonoids have beneficial effects on blood pressure in intervention settings, but there is limited information on habitual intake and risk of hypertension in population-based studies.
We examined the association between habitual flavonoid intake and incident hypertension in a prospective study in men and women.
A total of 87,242 women from the Nurses' Health Study (NHS) II, 46,672 women from the NHS I, and 23,043 men from the Health Professionals Follow-Up Study (HPFS) participated in the study. Total flavonoid and subclass intakes were calculated from semiquantitative food-frequency questionnaires collected every 4 y by using an updated and extended US Department of Agriculture database.
During 14 y of follow-up, 29,018 cases of hypertension in women and 5629 cases of hypertension in men were reported. In pooled multivariate-adjusted analyses, participants in the highest quintile of anthocyanin intake (predominantly from blueberries and strawberries) had an 8% reduction in risk of hypertension [relative risk (RR): 0.92; 95% CI: 0.86, 0.98; P < 0.03] compared with that for participants in the lowest quintile of anthocyanin intake; the risk reduction was 12% (RR: 0.88; 95% CI: 0.84, 0.93; P < 0.001) in participants ≤60 y of age and 0.96 (0.91, 1.02) in participants >60 y of age (P for age interaction = 0.02). Although intakes of other subclasses were not associated with hypertension, pooled analyses for individual compounds suggested a 5% (95% CI: 0.91, 0.99; P = 0.005) reduction in risk for the highest compared with the lowest quintiles of intake of the flavone apigenin. In participants ≤60 y of age, a 6% (95% CI: 0.88, 0.97; P = 0.002) reduction in risk was observed for the flavan-3-ol catechin when the highest and the lowest quintiles were compared.
Anthocyanins and some flavone and flavan-3-ol compounds may contribute to the prevention of hypertension. These vasodilatory properties may result from specific structural similarities (including the B-ring hydroxylation and methyoxylation pattern).
There are insufficient data to provide conclusive evidence on the health effects of most flavonoid subclasses. Future research of polyphenol bioactivity requires a more complete understanding of their intake, bioavailability and metabolism. The following summarises the limitations of polyphenol research as described across various reviews throughout the literature and presents the key requirements for future research. These include establishing the effects of processing, bioavailability and metabolism, developing physiologically appropriate in vitro models, standard methods of analysis and appropriate clinical biomarkers. The future of flavonoid research will undoubtedly depend upon the resolve of these issues, and although the field has shown continuous progress for many years, progress will likely slow if these challenges are not met.
Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release.
Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K) inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism.
These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.
Dark chocolate and flavanol-rich cocoa products have attracted interest as an alternative treatment option for hypertension, a known risk factor for cardiovascular disease. Previous meta-analyses concluded that cocoa-rich foods may reduce blood pressure. Recently, several additional trials have been conducted with conflicting results. Our study summarises current evidence on the effect of flavanol-rich cocoa products on blood pressure in hypertensive and normotensive individuals.
We searched Medline, Cochrane and international trial registries between 1955 and 2009 for randomised controlled trials investigating the effect of cocoa as food or drink compared with placebo on systolic and diastolic blood pressure (SBP/DBP) for a minimum duration of 2 weeks. We conducted random effects meta-analysis of all studies fitting the inclusion criteria, as well as subgroup analysis by baseline blood pressure (hypertensive/normotensive). Meta-regression analysis explored the association between type of treatment, dosage, duration or baseline blood pressure and blood pressure outcome. Statistical significance was set at P < 0.05.
Fifteen trial arms of 13 assessed studies met the inclusion criteria. Pooled meta-analysis of all trials revealed a significant blood pressure-reducing effect of cocoa-chocolate compared with control (mean BP change +/- SE: SBP: -3.2 +/- 1.9 mmHg, P = 0.001; DBP: -2.0 +/- 1.3 mmHg, P = 0.003). However, subgroup meta-analysis was significant only for the hypertensive or prehypertensive subgroups (SBP: -5.0 +/- 3.0 mmHg; P = 0.0009; DBP: -2.7 +/- 2.2 mm Hg, P = 0.01), while BP was not significantly reduced in the normotensive subgroups (SBP: -1.6 +/- 2.3 mmHg, P = 0.17; DBP: -1.3 +/- 1.6 mmHg, P = 0.12). Nine trials used chocolate containing 50% to 70% cocoa compared with white chocolate or other cocoa-free controls, while six trials compared high- with low-flavanol cocoa products. Daily flavanol dosages ranged from 30 mg to 1000 mg in the active treatment groups, and interventions ran for 2 to 18 weeks. Meta-regression analysis found study design and type of control to be borderline significant but possibly indirect predictors for blood pressure outcome.
Our meta-analysis suggests that dark chocolate is superior to placebo in reducing systolic hypertension or diastolic prehypertension. Flavanol-rich chocolate did not significantly reduce mean blood pressure below 140 mmHg systolic or 80 mmHg diastolic.
A number of databases on the plant metabolome describe the chemistry and biosynthesis of plant chemicals. However, no such database is specifically focused on foods and more precisely on polyphenols, one of the major classes of phytochemicals. As antioxidants, polyphenols influence human health and may play a role in the prevention of a number of chronic diseases such as cardiovascular diseases, some cancers or type 2 diabetes. To determine polyphenol intake in populations and study their association with health, it is essential to have detailed information on their content in foods. However this information is not easily collected due to the variety of their chemical structures and the variability of their content in a given food. Phenol-Explorer is the first comprehensive web-based database on polyphenol content in foods. It contains more than 37,000 original data points collected from 638 scientific articles published in peer-reviewed journals. The quality of these data has been evaluated before they were aggregated to produce final representative mean content values for 502 polyphenols in 452 foods. The web interface allows making various queries on the aggregated data to identify foods containing a given polyphenol or polyphenols present in a given food. For each mean content value, it is possible to trace all original content values and their literature sources. Phenol-Explorer is a major step forward in the development of databases on food constituents and the food metabolome. It should help researchers to better understand the role of phytochemicals in the technical and nutritional quality of food, and food manufacturers to develop tailor-made healthy foods. Database URL: http://www.phenol-explorer.eu.
Genistein, a component of soy products, may play a role in the prevention of breast and prostate cancer. However, little is
known about the molecular mechanisms involved. In the present study, we examined the effects of genistein on the estrogen
receptor positive human breast cancer cell line MCF-7. We observed that genistein stimulated estrogen-responsive pS2 mRNA
expression at concentrations as low as 10−8 M and these effects can be inhibited by tamoxifen. We also showed that genistein competed with (3H)estradiol binding to the estrogen receptor with 50% inhibition at 5 × 10−7 M. Thus, the estrogenic effect of genistein would appear to be a result of an interaction with the estrogen receptor. The
effect of genistein on growth of MCF-7 cells was also examined. Genistein produceda concentration-dependent effect on the
growth of MCF-7 cells. At lower concentrations (10−8-10−6 M) genistein stimulated growth, but at higher concentrations (>10−5M) genistein inhibited growth. The effects of genistein on growth at lower concentrations appeared to be via the estrogen
receptor pathway, while the effects at higher concentrations were independent of the estrogen receptor. We also found that
genistein, thoughestrogenic, can interfere with the effects of estradiol. In addition, prolonged exposure to genistein resulted
in a decrease in estrogen receptor mRNA level as well as a decreased response to stimulation by estradiol.
Background: The flavonoid components of tea have been associated in epidemiological studies with a decreased risk of cardiovascular disease. Flavonoids have been shown to have antioxidant and vasodilator effects in vitro; we therefore postulated that drinking green or black tea attenuates the well-characterized acute pressor response to caffeine and lowers blood pressure during regular consumption.
Objective: To determine whether green and black tea can attenuate the transient pressor effect of caffeine, or lower blood pressure during regular consumption.
Methods: In the first study, the acute effects of four hot drinks - green tea and black tea (at a dose equivalent to four standard cups), water matched to the teas for caffeine content ('caffeine') and water - were assessed in 20 normotensive men using a Latin-Square designed study. Clinic blood pressure was measured before and 30 and 60 min after each drink had been ingested. In the second study, the effects on blood pressure of regular green and black tea ingestion were examined in 13 subjects with high-normal systolic blood pressure and mild systolic hypertension (systolic blood pressure in the range 130-150 mmHg) using a three-period crossover study. Five cups per day of green tea, black tea and caffeine (in hot water and matched to the teas) were consumed for 7 days each, in random order. Twenty-four hour ambulatory blood pressure was measured at the end of each seven-day intervention. Results are presented as means and 95% confidence intervals (CI).
Results: An acute pressor response to caffeine was observed. Relative to caffeine, there were further acute increases in systolic and diastolic blood pressure at 30 min among those drinking green tea [5.5 mmHg (95%CI -21.4 to 12.4) and 3.1 mmHg (95%CI -0.1 to 6.3), respectively] and black tea [10.7 mmHg (95%CI 4.0 to 17.4) and 5.1 mmHg (95%CI 1.8 to 8.4), respectively]. The changes in blood pressure at 60 min were not significant. The effect on 24-h ambulatory systolic and diastolic blood pressure of regular drinking of green tea [increases of 1.7 mmHg (95%CI -1.6 to 5.0) and 0.9 mmHg (95%CI -1.3 to 3.1), respectively] or black tea [increase of 0.7 mmHg (95%CI -2.6 to 4.0) and decrease of 0.7 mmHg (95%CI -2.9 to 1.5), respectively] was not significant relative to caffeine.
Conclusions: Contrary to our initial hypothesis, tea ingestion caused larger acute increases in blood pressure than caffeine alone. However, any acute effects of tea on blood pressure did not translate into significant alterations in ambulatory blood pressure during regular tea consumption.
A growing body of evidence suggests that the consumption of foods rich in polyphenolic compounds, particularly cocoa, may have cardioprotective effects. No review, however, has yet examined the effect of flavonoid-rich cocoa (FRC) on all major cardiovascular risk factors or has examined potential dose-response relationships for these effects. A systematic review and meta-analysis of randomized, controlled trials was performed to evaluate the effect of FRC on cardiovascular risk factors and to assess a dose-response relationship. Inclusion and exclusion criteria as well as dependent and independent variables were determined a priori. Data were collected for: blood pressure, pulse, total cholesterol, HDL cholesterol, LDL cholesterol, TG, BMI, C-reactive protein, flow-mediated vascular dilation (FMD), fasting glucose, fasting insulin, serum isoprostane, and insulin sensitivity/resistance indices. Twenty-four papers, with 1106 participants, met the criteria for final analysis. In response to FRC consumption, systolic blood pressure decreased by 1.63 mm Hg (P = 0.033), LDL cholesterol decreased by 0.077 mmol/L (P = 0.038), and HDL cholesterol increased by 0.046 mmol/L (P = 0.037), whereas total cholesterol, TG, and C-reactive protein remained the same. Moreover, insulin resistance decreased (HOMA-IR: -0.94 points; P < 0.001), whereas FMD increased (1.53%; P < 0.001). A nonlinear dose-response relationship was found between FRC and FMD (P = 0.004), with maximum effect observed at a flavonoid dose of 500 mg/d; a similar relationship may exist with HDL cholesterol levels (P = 0.06). FRC consumption significantly improves blood pressure, insulin resistance, lipid profiles, and FMD. These short-term benefits warrant larger long-term investigations into the cardioprotective role of FRC.
LC-MS(n) and direct infusion-MS(n) have been applied for the first time to the characterisation of crude thearubigins isolated from black tea. The data generated have been used to test two hypotheses of thearubigin structure: (i) that a significant fraction of the thearubigins consist of polyhydroxylated derivatives of the better-known catechin dimers (theaflavins, theaflavin mono- and di-gallates, theacitrins) in redox equilibrium with their associated quinones; and (ii) that a significant fraction of the thearubigins consist of dicarboxylic acids generated by oxidative cleavage of aromatic diols. The data were consistent with the polyhydroxylation hypothesis and did not support the dicarboxylic acid hypothesis. Evidence is presented for the presence in crude thearubigins of at least 29 hydroxylated theaflavins (with between one and six oxygen insertions), at least 12 theaflavin mono-gallates (with between one and six oxygen insertions), at least nine theaflavin di-gallates (with between one and four oxygen insertions), and at least ten theacitrin mono-gallates (with between one and four oxygen insertions). Evidence is also presented for at least ten mono- or di-quinone forms of the parent compounds and hydroxylated derivatives in each of these homologous series. A general method for the analysis of complex mixtures by tandem LC-MS is furthermore introduced and established.
This paper reviews recent human studies on the bioavailability of dietary flavonoids and related compounds, including chlorogenic acids and ellagitannins, in which the identification of metabolites, catabolites and parent compounds in plasma, urine and ileal fluid was based on mass spectrometric methodology. Compounds absorbed in the small intestine appear in the circulatory system predominantly as glucuronide, sulfate and methylated metabolites which seemingly are treated by the body as xenobiotics as they are rapidly removed from the bloodstream. As a consequence, while analysis of plasma provides valuable information on the identity and pharmacokinetic profiles of circulating metabolites after acute supplementation, it does not provide accurate quantitative assessments of uptake from the gastrointestinal tract. Urinary excretion, of which there are great variations with different classes of flavonoids, provides a more realistic figure but, as this does not include the possibility of metabolites being sequestered in body tissues, this too is an under estimate of absorption, but to what degree remains to be determined. Even when absorption occurs in the small intestine, feeding studies with ileostomists reveal that substantial amounts of the parent compounds and some of their metabolites appear in ileal fluid indicating that in volunteers with a functioning colon these compounds will pass to the large intestine where they are subjected to the action of the colonic microflora. A diversity of colonic-derived catabolites is absorbed into the bloodstream and passes through the body prior to excretion in urine. There is growing evidence that these compounds, which were little investigated until recently, are produced in quantity in the colon and form a key part of the bioavailability equation of dietary flavonoids and related phenolic compounds.
Experimental models of stroke provide consistent evidence of smaller stroke volumes in animals ingesting tea components or tea extracts. To assess whether a similar association of black or green tea consumption with reduced risk is evident in human populations, we sought to identify and summarize all human clinical and observational data on tea and stroke.
We searched PubMed and Web of Science for all studies on stroke and tea consumption in humans with original data, including estimation or measurement of tea consumption and outcomes of fatal or nonfatal stroke. Data from 9 studies involving 4378 strokes among 194 965 individuals were pooled. The main outcome was the occurrence of fatal or nonfatal stroke. We tested for heterogeneity and calculated the summary effect estimate associated with consumption of >or=3 cups of tea (green or black) per day using random-effects and fixed-effects models for the homogeneous studies. Publication bias was also evaluated.
Regardless of their country of origin, individuals consuming >or=3 cups of tea per day had a 21% lower risk of stroke than those consuming <1 cup per day (absolute risk reduction, 0.79; CI, 0.73 to 0.85). The proportion of heterogeneity not explained by chance alone was 23.8%.
Although a randomized clinical trial would be necessary to confirm the effect, this meta-analysis suggests that daily consumption of either green or black tea equaling 3 cups per day could prevent the onset of ischemic stroke.
Glycyrrhizin is a major constituent of Kanzo, a popular herbal medicine used in food and cosmetics. Glycyrrhizin alone did not stimulate nitric oxide (NO) or prostaglandin E2 (PGE2) production by RAW 264.7 cells, but modified lipopolysaccharide (LPS)-stimulated NO and PGE2 production in a bimodal fashion: it was stimulatory at lower concentrations, whereas it was inhibitory at higher concentrations. Electron-spin resonance spectroscopy showed that glycyrrhizin slightly scavenged the superoxide anion generated by hypoxanthine-xanthine oxidase reaction, but did not scavenge the DPPH and NO radicals. The present study demonstrates the concentration-dependent action of glycyrrhizin on both PGE2 and NO production by activated macrophages.
Human intervention studies have provided clear evidence that dietary polyphenols (eg, flavonoids--eg, flavonols--and isoflavones) are at least partly absorbed and that they have the potential to exert biological effects. Biological activity of polyphenols is often assessed by using cultured cells as tissue models; in almost all such studies, cells are treated with aglycones or polyphenol-rich extracts (derived from plants and foods), and data are reported at concentrations that elicited a response. There are 2 inherent flaws in such an approach. First, plasma and tissues are not exposed in vivo to polyphenols in these forms. Several human studies have identified the nature of polyphenol conjugates in vivo and have shown that dietary polyphenols undergo extensive modification during first-pass metabolism so that the forms reaching the blood and tissues are, in general, neither aglycones (except for green tea catechins) nor the same as the dietary source. Polyphenols are present as conjugates of glucuronate or sulfate, with or without methylation of the catechol functional group. As a consequence, the polyphenol conjugates are likely to possess different biological properties and distribution patterns within tissues and cells than do polyphenol aglycones. Although deconjugation can potentially occur in vivo to produce aglycone, it occurs only at certain sites. Second, the polyphenol concentrations tested should be of the same order as the maximum plasma concentrations attained after a polyphenol-rich meal, which are in the range of 0.1-10 micromol/L. For correct interpretation of results, future efforts to define biological activities of polyphenols must make use of the available data concerning bioavailability and metabolism in humans.
Consumption of polyphenol-rich foods, such as fruits and vegetables, and beverages derived from plants, such as cocoa, red wine and tea, may represent a beneficial diet in terms of cardiovascular protection. Indeed, epidemiological studies demonstrate a significant inverse correlation between polyphenol consumption and cardiovascular risk. Among the numerous plausible mechanisms by which polyphenols may confer cardiovascular protection, improvement of the endothelial function and inhibition of angiogenesis and cell migration and proliferation in blood vessels have been the focus of recent studies. These studies have indicated that, in addition to and independently from their antioxidant effects, plant polyphenols (1) enhance the production of vasodilating factors [nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin] and inhibit the synthesis of vasoconstrictor endothelin-1 in endothelial cells; and (2) inhibit the expression of two major pro-angiogenic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in smooth muscle cells. The mechanisms of these effects involve: (1) in endothelial cells, increased Ca(2+) level and redox-sensitive activation of the phosphoinositide 3 (PI3)-kinase/Akt pathway (leading to rapid and sustained activation of nitric oxide synthase and formation of EDHF) and enhanced expression of nitric oxide synthase; and (2) in smooth muscle cells, both redox-sensitive inhibition of the p38 mitogen-activated protein kinase (p38 MAPK) pathway activation (leading to inhibition of platelet-derived growth factor (PDGF)-induced VEGF gene expression) and redox-insensitive mechanisms (leading to inhibition of thrombin-induced MMP-2 formation). The current evidence suggests that all these mechanisms are triggered by polyphenols with specific structures, although the structural requirements may be different from one effect to the other, and that they all contribute to the vasoprotective, anti-angiogenic, anti-atherogenic, vasorelaxant and anti-hypertensive effects of acute or chronic administration of plant polyphenols found in vivo in animals and in patients.
The beneficial effects of flavonoid consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence.
We aimed to systematically review the effectiveness of different flavonoid subclasses and flavonoid-rich food sources on cardiovascular disease (CVD) and risk factors--ie, lipoproteins, blood pressure, and flow-mediated dilatation (FMD).
Methods included a structured search strategy on MEDLINE, EMBASE, and Cochrane databases; formal inclusion or exclusion, data extraction, and validity assessment; and meta-analysis.
One hundred thirty-three trials were included. No randomized controlled trial studied effects on CVD morbidity or mortality. Significant heterogeneity confirmed differential effects between flavonoid subclasses and foods. Chocolate increased FMD after acute (3.99%; 95% CI: 2.86, 5.12; 6 studies) and chronic (1.45%; 0.62, 2.28; 2 studies) intake and reduced systolic (-5.88 mm Hg; -9.55, -2.21; 5 studies) and diastolic (-3.30 mm Hg; -5.77, -0.83; 4 studies) blood pressure. Soy protein isolate (but not other soy products or components) significantly reduced diastolic blood pressure (-1.99 mm Hg; -2.86, -1.12; 9 studies) and LDL cholesterol (-0.19 mmol/L; -0.24, -0.14; 39 studies). Acute black tea consumption increased systolic (5.69 mm Hg; 1.52, 9.86; 4 studies) and diastolic (2.56 mm Hg; 1.03, 4.10; 4 studies) blood pressure. Green tea reduced LDL (-0.23 mmol/L; -0.34, -0.12; 4 studies). For many of the other flavonoids, there was insufficient evidence to draw conclusions about efficacy.
To date, the effects of flavonoids from soy and cocoa have been the main focus of attention. Future studies should focus on other commonly consumed subclasses (eg, anthocyanins and flavanones), examine dose-response effects, and be of long enough duration to allow assessment of clinically relevant endpoints.