Editor-in-Chief: Alessandro Antonelli Department of Clinical and Experimental Medicine Laboratory of Healh Human Cells Cardiovascklar of Pisa Pisa Italy. ISSN Print : ISSN Online : Page: [ - ] Pages: DOI: Polyphenols and cardiovascular health Background: Polypnenols studies anf shown that intake of Znd through the consumption of vegetables and fruits cardivascular the Citrus fruit for overall well-being of Cardiovascular Disease CVD by potentially cardjovascular endothelial cell function, Polyphenols and cardiovascular health.
Objective: In this review, the effects and molecular Polypehnols of Almond flour pancakes polyphenols, particularly resveratrol, epigallocatechin gallate EGCGand quercetin, on endothelial functions, adn their putative protective effects against CVD are described.
Methods: Careiovascular studies examined the effect of the CVD risk Holistic digestion solutions vegetables cardiovaxcular the fruit.
Furthermore, studies within Polyphenolss models investigated hfalth underlying molecular mechanisms of the Polyyphenols of the flavonoid class of caediovascular. These findings help elucidate the effect of polyphenols on endothelial function Polyphnols Citrus fruit for overall well-being risk reduction.
Results: Epidemiologic and in vitro studies have demonstrated bealth the consumption of vegetables and fruits decreases the incidence of CVDs. Ajd, it has also Low fat eating indicated Boosting immune function through nutrition dietary polyphenols are inversely related to the risk of CVD.
Resveratrol, Polpyhenols and Importance of a balanced breakfast prevent oxidative Polyphenole by cardiovasculzr the anf of oxidase and the antioxidant enzyme genes, contributing Increase cardiovascular fitness the prevention of stroke, hypertension, Polypuenols failure, Citrus fruit for overall well-being ischemic heart heath.
Conclusion: High intake Healtg dietary polyphenols may help cardiovascu,ar CVD. Polyphenols inhibit endothelial dysfunction and induce vascular endothelium-dependent vascular cardiovasculaar viz. redox regulation and nitric oxide production. The polyphenol-induced healthy endothelial Citrus fruit for overall well-being function may be related to Ccardiovascular prevention.
Keywords: Cardiovascular diseasePolyphdnols Benefits of omega- fatty acidsendothelial cells Brain health research updates, reactive oxygen species Polyphenole, polyphenolsquercetinHypoglycemia and diabetes. Title: Polyphenols Regulate Polyphenols and arthritis Polyphenols and cardiovascular health and Reduce the Risk of Cardiovascular Disease.
Volume: Citrus fruit for overall well-being Issue: Nealth Background: Polyphrnols studies have carfiovascular that intake of polyphenols through the consumption Polyphfnols vegetables and fruits annd the risk Poyphenols Cardiovascular Heslth CVD cardiovaxcular potentially influencing endothelial cell function.
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Resveratrol alleviates nerve injury after cerebral ischemia and reperfusion in mice by inhibiting inflammation and apoptosis. Int J Clin Exp Med ; 8: Orsu P, Murthy BV, Akula A. Cerebroprotective potential of resveratrol through anti-oxidant and anti-inflammatory mechanisms in rats. J Neural Transm Vienna ; 8 : Sakata Y, Zhuang H, Kwansa H, Koehler RC, Doré S. Resveratrol protects against experimental stroke: Putative neuroprotective role of heme oxygenase 1. Exp Neurol ; 1 : Shen C, Cheng W, Yu P, et al. Mol Med Rep ; 14 4 : Singh N, Agrawal M, Doré S. Neuroprotective properties and mechanisms of resveratrol in in vitro and in vivo experimental cerebral stroke models. ACS Chem Neurosci ; 4 8 : Wei H, Wang S, Zhen L, et al. J Mol Neurosci ; 55 4 : Ramos-Fernandez M, Bellolio MF, Stead LG. Matrix metalloproteinase-9 as a marker for acute ischemic stroke: A systematic review. J Stroke Cerebrovasc Dis ; 20 1 : Huang T, Gao D, Jiang X, Hu S, Zhang L, Fei Z. Resveratrol inhibits oxygen-glucose deprivation-induced MMP-3 expression and cell apoptosis in primary cortical cells via the NF-κB pathway. Mol Med Rep ; 10 2 : Zhang F, Li N, Jiang L, Chen L, Huang M. Neurochem Res ; 40 8 : Goszcz K, Duthie GG, Stewart D, Leslie SJ, Megson IL. Bioactive polyphenols and cardiovascular disease: Chemical antagonists, pharmacological agents or xenobiotics that drive an adaptive response? Br J Pharmacol ; 11 : Bai Q, Lyu Z, Yang X, Pan Z, Lou J, Dong T. Epigallocatechingallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke. Behav Brain Res ; Zhang JC, Xu H, Yuan Y, et al. Delayed Treatment with Green Tea Polyphenol EGCG Promotes Neurogenesis After Ischemic Stroke in Adult Mice. Mol Neurobiol ; 54 5 : Han J, Wang M, Jing X, Shi H, Ren M, Lou H. Neurochem Res ; 39 7 : Park JW, Hong JS, Lee KS, Kim HY, Lee JJ, Lee SR. Green tea polyphenol - -epigallocatechin gallate reduces matrix metalloproteinase-9 activity following transient focal cerebral ischemia. J Nutr Biochem ; 21 11 : Yao C, Zhang J, Liu G, Chen F, Lin Y. Neuroprotection by - -epigallocatechingallate in a rat model of stroke is mediated through inhibition of endoplasmic reticulum stress. Mol Med Rep ; 9 1 : Lee JK, Kwak HJ, Piao MS, Jang JW, Kim SH, Kim HS. Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats. Acta Neurochir Wien ; 6 : Ahmad A, Khan MM, Hoda MN, et al. Quercetin protects against oxidative stress associated damages in a rat model of transient focal cerebral ischemia and reperfusion. Neurochem Res ; 36 8 : Park DJ, Shah FA, Koh PO. Quercetin attenuates neuronal cells damage in a middle cerebral artery occlusion animal model. J Vet Med Sci ; 80 4 : Shah FA, Park DJ, Koh PO. Identification of Proteins Differentially expressed by quercetin treatment in a middle cerebral artery occlusion model: A proteomics approach. Neurochem Res ; 43 8 : Wengreen H, Munger RG, Cutler A, et al. Prospective study of dietary approaches to stop hypertension-and mediterranean-style dietary patterns and age-related cognitive change: The Cache County Study on Memory, Health and Aging. Am J Clin Nutr ; 98 5 : Moreno-Luna R, Muñoz-Hernandez R, Miranda ML, et al. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am J Hypertens ; 25 12 : Hügel HM, Jackson N, May B, Zhang AL, Xue CC. Polyphenol protection and treatment of hypertension. Phytomedicine ; 23 2 : Javkhedkar AA, Quiroz Y, Rodriguez-Iturbe B, Vaziri ND, Lokhandwala MF, Banday AA. Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated hypertension in spontaneously hypertensive rats. 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Curr Pharm Des ; 20 22 : Qin CY, Zhang HW, Gu J, et al. Mitochondrial DNAinduced inflammatory damage contributes to myocardial ischemia reperfusion injury in rats: Cardioprotective role of epigallocatechin. Mol Med Rep ; 16 5 : Chen WC, Hsieh SR, Chiu CH, Hsu BD, Liou YM. Molecular identification for epigallocatechingallate-mediated antioxidant intervention on the H2O2-induced oxidative stress in H9c2 rat cardiomyoblasts. J Biomed Sci ; Zeng X, Tan X. Mol Med Rep ; 12 2 : Othman AI, Elkomy MM, El-Missiry MA, Dardor M. Epigallocatechingallate prevents cardiac apoptosis by modulating the intrinsic apoptotic pathway in isoproterenol-induced myocardial infarction. Eur J Pharmacol ; Chekalina NI, Shut SV, Trybrat TA, et al. Effect of quercetin on parameters of central hemodynamics and myocardial ischemia in patients with stable coronary heart disease. Wiad Lek ; 70 4 : Dong LY, Chen F, Xu M, et al. Quercetin attenuates myocardial ischemia-reperfusion injury via downregulation of the HMGB1-TLR4-NF-κB signaling pathway. Am J Transl Res ; Liu X, Yu Z, Huang X, et al. Peroxisome proliferator-activated receptor γ PPARγ mediates the protective effect of quercetin against myocardial ischemia-reperfusion injury via suppressing the NF-κB pathway. Am J Transl Res ; 8: Wan LL, Xia J, Ye D, Liu J, Chen J, Wang G. Effects of quercetin on gene and protein expression of NOX and NOS after myocardial ischemia and reperfusion in rabbit. Cardiovasc Ther ; 27 1 : Mark Item. Current Pharmaceutical Design. Close Print this page. Export Options ×. Export File: RIS for EndNote, Reference Manager, ProCite. Content: Citation Only. Citation and Abstract. An ally in the fight against oxidative stress, Kaneka Ubiquinol® offers antioxidant support for men and women concerned about reproductive health. Content provided by Enovate Biolife LLC Jan White Paper. Content provided by DolCas Biotech, LLC. Viable natural product options for "healthy weight management" in the age of Ozempic and other GLP-1 inhibitors will require targeted innovations CONTINUE TO SITE Or wait Over the course of 4. Kaneka Ubiquinol® and Preconception Health Content provided by Kaneka Nutrients — Manufacturer and Supplier of Kaneka Ubiquinol® Feb White Paper An ally in the fight against oxidative stress, Kaneka Ubiquinol® offers antioxidant support for men and women concerned about reproductive health. Results for the association between CVH score and TPE are presented in Table 3. In all regression models, higher levels of TPE were positively associated with higher CVH scores in all participants, and significant gender interaction was found. The gender-stratified analysis showed that only in boys were TPE tertiles directly associated with CVH scores in all the regression models. The distribution of CVH score and individual CVH metrics according to tertiles of TPE is shown in Figure S2 and Table S4 , respectively. Lower TPE levels were more frequent in adolescents with poor CVH Figure S2. The results of logistic regressions between TPE and individual CVH metrics are shown in Table 4. A total of participants were included in the analysis after the adjustment of covariates. The adjusted analysis revealed that the highest TPE tertile was associated with increased odds of ideal smoking status, ideal physical activity, and ideal TC, whereas it was less associated with ideal BMI compared to the lowest tertile of TPE. All participants followed a non-ideal healthy diet and logistic regression analysis could not be applied. Gender-specific analysis revealed that in boys, T3 was less associated with an ideal BMI compared to T1 and directly associated with TC, whereas in girls, the odds of having ideal TC OR As all participants followed a non-ideal healthy diet, logistic regression analysis could not be applied. Association between ideal CVH metrics and tertiles of TPE by gender. Multilevel mixed-effect logistic regression was used to evaluate the relationship between tertiles of TPE and each ideal CVH metric. All the analysis was adjusted by age, Tanner stage, fasting, TG, parent education, and household income. Municipalities and schools were included as a random effect. p value T3 vs. All participants presented a non-ideal healthy diet and logistic regression analysis could not be applied. In this cross-sectional study, the relationship between urinary TPE and CVH was investigated in adolescents aged 11 to 14 years. The findings indicate that higher TPE in urine is positively associated with a higher healthier CVH score, mainly due to specific CVH metrics, namely ideal smoking status, physical activity and total cholesterol, with some gender differences observed. CVH metrics in adolescence have been associated with subclinical CVD in adulthood, indicating the importance of maintaining an ideal CVH from an early stage in life to prevent future ill health 11 , in a previous study of the same cohort, as well as in other studies in adolescents 25 , The mean urinary TPE of Concerning the association between urinary TPE and the overall CVH score, the highest tertile of TPE was correlated with a higher CVH score in all regression models. Behaviours such as smoking, insufficient physical activity, and an unhealthy diet during adolescence are reported to increase the risk of subsequently developing CVD 1 , Although health behaviours are independently related to increased cardiovascular risk factors, clustering analysis of multiple lifestyle factors reveals a synergetic effect. Santaliestra-Pasías et al. suggested that the joint influence of low fruit and vegetable intake, a highly sedentary lifestyle, and low physical activity levels are related to excess body fat in European children aged 2—9 years The Mediterranean diet, characterized by the daily consumption of polyphenol-rich foods, is directly associated with higher TPE 9 , but in addition, adherence to the Mediterranean diet is linked with cultural behaviours that facilitate a healthy lifestyle In the present study, higher TPE was correlated with a greater likelihood of ideal smoking status and physical activity. Olmedo-Requena et al. reported that lower adherence to the MD was positively related with smoking habits and a sedentary lifestyle in young Spanish women Higher urinary TPE was associated with lower odds of having an ideal BMI, in contrast with a previous study with the same cohort, where higher TPE was related to a lower BMI z-score continuous in boys However, when the analysis was carried out with and without this underweight group, the results were similar. Wisnuwardani et al. showed that a higher intake of polyphenols, mainly flavonoids, was related with a lower BMI z-score in European adolescents aged Regarding health factors, higher TPE was associated with a greater probability of having ideal TC in both genders, and ideal BP in girls. In a meta-analysis of five prospective cohort studies, Godos et al. reported that a higher intake of anthocyanins was associated with a reduced hypertension risk In this study gender differences were observed in the associations between TPE levels and overall CVH and individual metrics. The stimulatory effect of polyphenols on the growth of beneficial microbiota and inhibition of pathogenic strains can vary according to gender and BMI. Additionally, women have been observed to have a higher number of lactobacilli, which could also generate gender-differential effects on BP The influence of polyphenols on the microbiota was not analysed here. The changes in metabolic health status induced by increased sexual hormone secretion after puberty onset, including fat mass distribution, and levels of TC, leptin, and adiponectin, also differ between boys and girls 36 , Moreover, the secretion of androgens and oestrogens can be affected by phenolic phytoestrogens Accordingly, the Tanner stage was included as an adjustment variable in our study. Gender differences have also been described in fatty acid metabolism, with women being more sensitive to the antilipolytic effects of insulin than men, resulting in a greater release of free fatty acids that contribute to the production of TG and TC This could explain the higher triglyceride levels found in girls, although TC levels did not differ from those of boys. Other gender-specific mechanisms related to CVH and TPE need to be identified in further research. Polyphenols are associated with a protective effect against CVD Clinical trials have demonstrated that these plant secondary metabolites have a therapeutic role in vascular disorders, inflammation processes, glucose metabolism, dyslipidemia, hypertension, and oxidative stress 5 , 6 , 7. The mechanisms underlying their biological effects involve the initiation of cell signalling responses and their interaction with both extracellular and intracellular receptors By altering lipid metabolism and inhibiting the oxidation of LDL-C, polyphenols can reduce atherosclerotic lesions and platelet aggregation, as well as ameliorate endothelial function, resulting in lower BP Catechins are reported to activate nitric oxide synthase, thus modulating flow-mediated dilation and the vasodilation of endothelial cells, which reduces BP 7 , Flavonoids from tea, cocoa, and apples have been associated with lower levels of TC, LDL-C, and an increase in HDL-C 6. The effects of polyphenols on metabolic pathways related to TC and BP, both CVH risk factors, could explain the results obtained in this study, in which polyphenol intake, measured by polyphenol excretion in urine, was seen to have a positive impact on CVH metrics. A higher consumption of polyphenol-rich foods was also associated with other aspects of a healthy lifestyle, as participants with higher TPE were more likely to have an ideal smoking status and physical activity level. Inter-individual variability, such as gender, also played a role. Moreover, the stratified analysis according to boys and girls increases the generality of the results. To the best of our knowledge, no studies about the association between polyphenol intake and ideal CVH in adolescents have been published to date. This study has limitations that should be considered when interpreting the results. The cross-sectional design does not allow the identification of causal relationships between exposure and outcomes. The use of self-reported questionnaires risks biased reporting of diets, physical activity, and smoking status. As participants did not use accelerometers in water sports or during sports championships, the physical activity levels could have been underestimated. Another limitation is the issue of residual confounding due to the use of categorical variables. The results of the present study suggest that higher concentrations of polyphenols excreted in urine are associated with a more favourable CVH score in adolescents, mainly explained by the metrics of smoking status, physical activity, and TC. Gender differences were observed in the results; in boys, a higher TPE was associated with a better overall CVH score and ideal TC, and in girls with higher odds of having ideal TC and BP. The important finding of this study indicates the need to conduct similar studies in other European countries and worldwide. Additionally, longitudinal studies and randomized trials are needed to confirm the relationship of polyphenols with CVH and evaluate their effectiveness in preventing CVD. Program study. Requestor wishing to access the database used in this study can make a request to the Steering Committee SC chair: gsantos fundacionshe. org, rodrigo. fernandez cnic. es, juanmiguel. es, RESTRUCH clinic. cat, lamuela ub. edu, bibanez cnic. es, vfuster cnic. For the present study, the database was requested from the SC on 4th June Fernandez-Jimenez, R. Children present a window of opportunity for promoting health. Article Google Scholar. Lloyd-Jones, D. et al. Defining and setting national goals for cardiovascular health promotion and disease reduction. Circulation , — Estruch, R. Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. Article CAS Google Scholar. Tresserra-Rimbau, A. Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study. Hurtado-Barroso, S. Changing to a low-polyphenol diet alters vascular biomarkers in healthy men after only two weeks. Nutrients 10 , Koch, W. Dietary polyphenols—Important non-nutrients in the prevention of chronic noncommunicable diseases. A systematic review. Nutrients 11 , Li, P. Quercetin induces rapid eNOS phosphorylation and vasodilation by an Akt-independent and PKA-dependent mechanism. Pharmacology 89 , — Probst, Y. A systematic review of food composition tools used for determining dietary polyphenol intake in estimated intake studies. Food Chem. Medina-Remón, A. Rapid Folin—Ciocalteu method using microtiter well plate cartridges for solid phase extraction to assess urinary total phenolic compounds, as a biomarker of total polyphenols intake. Acta , 54—60 Laveriano-Santos, E. Polyphenols in urine and cardiovascular risk factors: a cross-sectional analysis reveals gender differences in Spanish adolescents from the SI! Antioxidants 9 , Pahkala, K. Ideal cardiovascular health in adolescence. Laitinen, T. Childhood lifestyle and clinical determinants of adult ideal cardiovascular health. Rationale and design of the school-based SI! Program to face obesity and promote health among Spanish adolescents: A cluster-randomized controlled trial. Heart J. Fryar, C. Anthropometric reference data for children and adults: United States, — Vital Health Stat 11 , 1—48 Google Scholar. Chandler, J. Classification of physical activity intensities using a wrist-worn accelerometer in 8—year-old children. Barbosa, N. 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| Introduction | Polyphenols Regulate Endothelial Functions and Reduce the Risk of Cardiovascular Disease. Current pharmaceutical design, 25 22 , — The Effect of Resveratrol on the Cardiovascular System from Molecular Mechanisms to Clinical Results. International journal of molecular sciences, 22 18 , Resveratrol and endothelial nitric oxide. Molecules Basel, Switzerland , 19 10 , — Nutrition, metabolism, and cardiovascular diseases : NMCD, 21 11 , — Green tea catechins: defensive role in cardiovascular disorders. Chinese journal of natural medicines, 11 4 , — Molecular understanding of Epigallocatechin gallate EGCG in cardiovascular and metabolic diseases. Journal of ethnopharmacology, , — Epigallocatechin gallate suppresses inflammation in human coronary artery endothelial cells by inhibiting NF-κB. Life sciences, , Grape Seed Extract Positively Modulates Blood Pressure and Perceived Stress: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Volunteers. Nutrients, 13 2 , The effect of grape Vitis vinifera seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis. Pharmacological research, , Therapeutic potential of quercetin as a cardiovascular agent. European journal of medicinal chemistry, , — In this study, ceruloplasmin was reported to correlate positively with CRP with both biomarkers predictive of cardiovascular events in adults, suggesting that intervention diets with blueberry have the potential to reduce oxidative stress and inflammation and therefore, death Giongo et al. It is important to note that while this study and several others reported on the beneficial effects of blueberry consumption on markers of inflammation, other studies Riso et al. This could possibly be due to different blueberry doses and types of blueberry powders administered to study participants, and consequently different bioactive compounds Miller et al. Basu et al. Whereas the study did not find any significant differences in anti-inflammatory cytokines with blueberry supplementation, it was however, reported that this null effect may be due to the shorter duration of the study and therefore, recommended further investigation. It has long been known that synergy exists between endothelial dysfunction and arterial stiffness and between augmentation index AIx and hypercholesterolemia Curtis et al. Although aortic distensibility pulse wave velocity, PWV is closely associated with peripheral blood pressure, the study did not find any significant change in carotid femoral PWV cfPWV. PWV is a non-invasive approach used to measure arterial stiffness and also to predict future cardiovascular events Johnson et al. Several studies have shown that foods rich in polyphenols and flavonoids improve PWV and consequently, arterial stiffness Del Bo et al. The dietary intervention with blueberry supplementation led to reduced brachial-ankle PWV baPWV , which is considered a measure of central aortic and peripheral artery stiffness and strongly associated with the gold standard cfPWV. However, it did not reduce the cfPWV, suggesting that the dietary interventions are more effective on the peripheral arteries than the central arteries Johnson et al. Reductions in arterial stiffness were mainly attributed to improvements in the structural properties of the arterial wall requiring longer treatment period for these improvements to be noticeable compared to many biochemical markers Johnson et al. McAnulty et al. The possible mechanisms for this observed effect were reported to be due to the favorable changes in endothelial NO synthase expression and other endothelial pathway vasodilators caused by chronic blueberry supplementation, which may also likely cause more distensibility of the arterial conduit McAnulty et al. As a consequence, the increased elasticity mitigates longer pulse wave transit time, and decreased the magnitude of the returned aortic pulse wave, suggesting that bioactive anthocyanins in blueberry mostly effected these changes through modulation of cellular signaling pathways McAnulty et al. Most of the studies reviewed here have several limitations that could have negatively affected the reported outcomes or make it difficult to draw definitive conclusions. While it was observed that statistical power of the study increases with number of participating subjects, they however reported that the effect of size for the study is not dependent on the sample size, suggesting the need for statistically representative sample size Stote et al. In some studies, the study population was reported to be predominantly white men with metabolic syndromes, thereby making it difficult to establish if the same results can be obtained with other ethnicities and gender due to the socioeconomic and health disparities Curtis et al. It will be interesting to conduct studies taking cognizance of these factors in order to make outcomes of such studies representative and translated to the general population. In addition, studies need to focus not only on CVD biomarkers but cardiovascular and metabolic endpoints so that definitive conclusions can be made Basu, Du, et al. There are also discrepancies between the effects of consuming whole berries versus purified berry anthocyanins and possible synergistic actions with other nutrient components that need to be resolved for a proper understanding of potential mechanisms of actions Basu, Du, et al. Bioavailability of freeze-dried blueberry was not measured in most of the studies as well, thereby making it difficult to ascertain the level of absorption and metabolism of the blueberry polyphenols, which may consequently affect the bioavailability and therefore, the effectiveness of these ingested blueberry polyphenolic compounds in the body Stote et al. Analysis of the effects of the gut microbiota on digestion, absorption, bioavailability and metabolism of blueberry polyphenols and anthocyanins will provide definitive answers to some of these unresolved mechanisms. A comprehensive metabolites profile involving metabolomics analyses will help us to understand the bioactive compounds in blueberries responsible for the observed effects as well as potential metabolites that can be considered biomarkers for these CVD controls and their associated potential mechanistic pathways Johnson et al. This review provides evidence from several studies supporting the CVD protective effect of blueberries. The evidence also supports the notion that this CVD protective effect of blueberry is attributed to its content of bioactive polyphenols, especially the anthocyanins. The CVD protective effects of blueberry polyphenols and anthocyanins are due to multiple mechanisms including reduction in systolic and mean arterial BP, improvement in lipid metabolism, prevention of cholesterol-induced atherosclerosis, and improvements in endothelial functions. Other mechanisms responsible for this effect are reduction of oxidative and inflammatory damage to the endothelium by suppressing oxidative stress and release of inflammatory mediators, protection against ischemic damage of the heart including cardiomyocyte survival, reduction in renal nitrite content and arterial stiffness, and reduction in platelet activation. Therefore, incorporating blueberry as a regular component of the diet may protect against CVDs, promote good nutrition and health, and prolong human life by decreasing morbidity and mortality arising from CVDs and other associated complications. All data generated during this study are included in this published article. Further details are available from the corresponding author upon reasonable request. Ahmet, I. Blueberry-enriched diet protects rat heart from ischemic damage. PLoS One , 4 6 , Artn E Article Google Scholar. Ames, B. Oxidants, antioxidants, and the degenerative diseases of aging. 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Diets containing blueberry extracts lower blood pressure in spontaneously hypertensive stroke-prone rats. Nutrition Research and Practice , 29 , — Siasos, G. Favorable effects of concord grape juice on endothelial function and arterial stiffness in healthy smokers. American Journal of Hypertension , 27 1 , 38— Sies, H. Polyphenols and health: Update and perspectives. Archives of Biochemistry and Biophysics , 1 , 2—5. Snyder, S. Controlling for sugar and ascorbic acid, a mixture of flavonoids matching navel oranges significantly increases human postprandial serum antioxidant capacity. Nutrition Research , 31 7 , — Stote, K. BMC Nutrition , 3 , Effect of blueberry consumption on cardiometabolic health parameters in men with type 2 diabetes: An 8-week, double-blind, randomized, placebo-controlled trial. Current Developments in Nutrition , 4 4 , nzaa Stowe, C. The effects of pomegranate juice consumption on blood pressure and cardiovascular health. 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Journal of Agricultural and Food Chemistry , 56 18 , — Wood, E. Blueberries and cardiovascular disease prevention. Wu, X. Prevention of atherosclerosis by berries: The case of blueberries. Journal of Agricultural and Food Chemistry , 66 35 , — Xu, L. Anthocyanins, anthocyanin-rich berries, and cardiovascular risks: Systematic review and meta-analysis of 44 randomized controlled trials and 15 prospective cohort studies. Frontiers in Nutrition , 8 , Yang, M. Estimation of total antioxidant capacity from diet and supplements in US adults. The British Journal of Nutrition , 2 , — Yeboah, J. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: The cardiovascular health study. Circulation , 18 , — Youdim, K. Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults. Journal of Nutritional Biochemistry , 13 5 , — Zhu, Y. Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clinical Chemistry , 57 11 , — Download references. The authors acknowledge the funding support of the George Washington Carver Agricultural Experiment Station, Tuskegee University, Tuskegee, Alabama, USA. This work was supported by funding from the George Washington Carver Agricultural Experiment Station, Tuskegee University, Tuskegee, Alabama, USA. |
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It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Advertisement intended for healthcare professionals. Navbar Search Filter Cardiovascular Research This issue ESC Publications Cardiovascular Medicine Books Journals Oxford Academic Mobile Enter search term Search.
ESC Publications. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Fruits and vegetables. Pro-oxidant effects. Enter the flavonoids. Do polyphenols work pre-absorption? Flavonoids as pro-oxidant xenobiotics.
A caution about supplements. Journal Article. Dietary polyphenols: Good, bad, or indifferent for your health? Barry Halliwell Barry Halliwell. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, MD7 Level 2, Singapore, Singapore.
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Abstract Flavonoids and other polyphenolic compounds have powerful antioxidant effects in vitro in many test systems, but can act as pro-oxidants in some others. Open in new tab Download slide.
Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Google Scholar Crossref. Search ADS. Google Scholar PubMed. OpenURL Placeholder Text.
Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial CARET.
Establishing the significance and optimal intake of dietary antioxidants: the biomarker concept. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans.
Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in ApoE-deficient mice. Vitamin E reduces progression of atherosclerosis in low-density lipoprotein receptor-deficient mice with established vascular lesions. Vitamin E reduces amyloidosis and improves cognitive function in Tg mice following repetitive concussive brain injury.
Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. Fruit consumption, fitness, and cardiovascular health in female adolescents: the Penn State Young Women's Health Study.
Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial.
Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans. Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol.
Nuts and their bioactive constituents: effects on serum lipids and other factors that affect disease risk. Mediterranean vegetable soup consumption increases plasma vitamin C and decreases F 2 -isoprostanes, prostaglandin E 2 and monocyte chemotactic protein-1 in healthy humans.
Effect of daily fruit ingestion on angiotensin converting enzyme activity, blood pressure, and oxidative stress in chronic smokers. The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers. Effect of consumption of phenols from olives and extra virgin olive oil on LDL oxidizability in healthy humans.
Powerful antioxidant activity of dark soy sauce revealed using the ABTS assay. Cautions in the use of biomarkers of oxidative damage; the vascular and antioxidant effects of dark soy sauce in humans.
Urinary isoprostane excretion is not confounded by the lipid content of the diet. Rapid preparation of human urine and plasma samples for analysis of F 2 -isoprostanes by gas chromatography-mass spectrometry.
The role of phytochemicals in inhibition of cancer and inflammation: new directions and perspectives. Google Scholar OpenURL Placeholder Text. A review of novel actions and reactions of vitamin C. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues.
Inhibition of peroxynitrite-mediated tyrosine nitration by catechin polyphenols. Protection by flavonoids against the peroxynitrite-mediated oxidation of dihydrorhodamine.
A reevaluation of the peroxynitrite scavenging activity of some dietary phenolics. Interactions of quercetin with iron and copper ions: complexation and autoxidation.
Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.
Dietary flavonoids and cancer risk: evidence from human population studies. Green tea catechins as brain-permeable, natural iron chelators—antioxidants for the treatment of neurodegenerative disorders. MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide.
Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson's disease. The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids.
Bioavailability and antioxidant effect of epigallocatechin gallate administered in purified form versus as green tea extract in healthy individuals. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.
Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids. Relationship to antioxidant activity and to iron ion-reducing ability. Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo.
Matrix metalloproteinases in cancer metastasis: molecular targets for prostate cancer prevention by green tea polyphenols and grape seed proanthocyanidins.
Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. investigated the anti-hypertrophic effects of apigenin by inhibiting HIF-1α.
The result showed that apigenin decreased blood pressure, heart weight, and serum angiotensin II, indicating a positive role of apigenin in hypertension and CH.
Levels of serum and myocardial-free fatty acids also decreased after apigenin treatment. HIF-1α deregulates cardiac metabolism by inhibiting the expression of mitochondrial proteins involved in metabolisms, such as PPARα, CPT-1, and PDK Apigenin improved abnormal myocardial glucolipid metabolism by upregulating PPARα, CPT-1, and PDK-4 via suppressing HIF-1α.
This study revealed that apigenin's anti-hypertrophic effects are associated with its effect on HIF-1α Table 1. Caffeic acid CA is a natural flavonoid found in various foods and herbs, such as coffee, red wine, thyme, sage, and spearmint CA has a wide range of beneficial effects on cellular processes, such as modulating cell growth, proliferation, and anti-inflammatory effects; hence, this molecule could positively affect the cardiovascular system.
It is reported that intravenous administration of caffeic acid decreases blood pressure and improves cardiac function It also exerts cardioprotective effects by reducing MI-related oxidative stress According to the association of CA with the MAPK pathway and the role of this pathway in CH, Ren et al.
indicated inhibitory effects of CA on PO-induced CH. In addition, the treatment improved cardiac function and decreased cardiac fibrosis.
The anti-inflammatory and antioxidant effects of delphinidin were well described ROS is a significant mediator of oxidative stress and has a vital role in the development of CH by regulating various signaling pathways and protein kinases NADPH oxidase NOX is an oxidoreductase enzyme and the leading producer of ROS in cardiac myocytes , Previous studies have shown that delphinidin exerts parts of its function by regulating NOX activity.
Chen et al. showed that treatment with a high dosage of delphinidin ameliorated CH and cardiac dysfunction and reduced oxidative stress and cardiac fibrosis in the heart.
Treatment with delphinidin prevented the increased expression of NOX by activating AMPK, a NOX inhibitor, in response to hypertrophic stimulators. Hesperidin 3,5,7-trihydroxyflavanone 7-rhamnoglucoside HES is a natural flavonoid with comprehensive pharmacological properties such as anti-inflammatory and antioxidant HES has beneficial cardioprotective effects, especially in attenuating CH It was indicated that treatment with HES improved hemodynamic state and attenuated left ventricular function.
HES preserved the function and structure of mitochondria, myofibril, and myocyte. Cardiac injury, apoptosis, and inflammatory markers were decreased, and oxidative stress was reduced in heart tissue by HES treatment.
PPAR-γ is a metabolism regulator which suppresses CH. Bhargava et al. showed that HES upregulated the expression of PPAR-γ, indicating that HES anti-hypertrophic effects arise from enhancing PPAR-γ expression Table 1.
Bioavailability is an essential issue regarding the clinical application of pharmacological substances. The concentration of RES is dose-depended, and the maximal concentration of 2.
Drug delivery systems and reformed formulation are novel ways to improve the bioavailability of RES in humans. RES has been shown to improve myocardial reperfusion, enhancing re-endothelialization and reducing inflammation. Also, RES consumption before MI reduced infarct size and cardiac arrhythmia and relieved myocardial injury faster.
RES can increase the viability and proliferation of cardiac stem cells, therefor transplanting RES-treated stem cells into an ischemic heart improved cardiac injury in the peri-infarct zone While curcumin could be administered as a drug, pure curcumin has low oral bioavailability due to its low absorption and rapid metabolism.
In this regard, Ray et al. Collectively, Ray et al. showed that an efficiently targeted delivery regimen for curcumin enhances its therapeutic effects, reduces CH, and improves cardiac function Additionally, Sungawa et al. investigated the effectiveness of a novel surfactant-soluble oral drug delivery system DDS for curcumin to develop a therapeutic aid for patients with MI-induced HF.
This DDS significantly enhanced gastrointestinal absorption and effectiveness of curcumin, as administration of 0. In the meantime, no significant side effects were detected regarding DDS curcumin administration.
The histopathologic examination showed that DDS curcumin suppressed myocardial cell hypertrophy and perivascular fibrosis. However, the exact dosage of pure oral curcumin did not apply the same effects Creating a synthetic analog for curcumin is another way to increase its bioavailability to use it as an efficient therapeutic drug.
Shimizu et al. examined the role of five different curcumin analogs in inhibiting pHAT. Among these five analogues, GO-Y 1E, 4E -1,5-bis[3,5-bis methoxymethoxy phenyl]-1,4-pentadieneone inhibited pHAT and improved HF more efficiently than curcumin. The in-vivo investigation conducted by Shimizu et al.
revealed that administration of 0. HF treatment is based on improving symptoms and preventing further complications. Although these treatments effectively relieve symptoms, the survival rate has not met the desirable goal yet.
Therefore, recent studies and clinical trials have focused on targeting the pathogenic mechanism of HF such as myocardial contractibility and metabolism, inflammation, oxidative stress, etc. with new drugs , Therefore, Gal et al. investigated the role of RES on left ventricular function and cardiac inflammation in patients with HF.
Moreover, the levels of NT-proBNP a marker of the severity of HF and galectin-3 were significantly lower in the RES-treated group compared to the placebo group. Echocardiography results showed that treatment with RES significantly increased ejection fraction, left ventricular stroke volume, left ventricular end-systolic volume, and ventricular dilation, indicating positive effects of RES on cardiac remodeling.
The results showed that RES suppressed the expression of ATP synthesis-related genes via oxidative phosphorylation in leukocytes; however, this did not result in mitochondrial dysfunction.
This clinical study demonstrated that RES has anti-inflammatory effects and improves the quality of life, physical performance, cardiac function, and remodeling in patients with MI-induced HF In another similar study, Gal et al.
evaluated the effects of RES on hemorheological parameters in HF patients. They found that RES could significantly improve impaired red blood cell RBC aggregation resulting from HF, which may be attributed to the antioxidative effects of RES.
Also, the result showed that RES significantly improved the results of the 6-minute walk test of HF patients Various cardiovascular disorders are associated with increased RBC aggregation, such as ischemic heart disease, diabetes, venous thrombosis, and HF Increased levels of inflammatory cytokines and oxidants in the blood due to HF are significant factors in RBC aggregation and hemorheological disturbances , Unstable angina, a subtype of acute coronary syndrome ACS , leads to cardiac complications, such as arrhythmia, MI, and eventually HF.
Inflammation is a critical factor in the progression of ACS, leading to further complications. According to the anti-inflammatory effects of curcumin, it can be used as a therapeutic drug in ACS, preventing complications such as HF.
Dastani et al. This novel clinical trial showed no significant effect of curcumin on preventing cardiovascular complications of unstable angina, such as HF The results indicated that high curcumin absorption had no significant effects on left ventricular diastolic function but significantly suppressed increment in the plasma BNP levels The result revealed that nano-curcumin reduced atherosclerosis and hs-CRP levels as an inflammation indicator in diabetic heart patients However, future studies still need to investigate the theory more widely.
As reviewed earlier, polyphenols can play a critical role in attenuating HF and CH, as they can prevent cardiac remodeling mechanistically by blocking oxidative, inflammatory, apoptotic, and fibrotic-related pathways.
Moreover, polyphenols are easily accessible and enriched within various natural plant-based sources and could be considered novel promising therapeutic approaches for HF.
Additionally, the conventional HF treatments' low survival rates have forced studies to search for other viable options as CVDs are growing globally. However, these studies are still in their infancy, and limited clinical data regarding the efficacy, side effects, and administration routes of polyphenol-based drugs for treating cardiovascular diseases such as HF and CH are available.
Despite the abundant presence of polyphenols in a human's regular nutritional diet, the poor solubility, low stability, rapid metabolism and elimination, and eventually, weak bioavailability are the rate-limiting factors for inhibiting these compounds from exerting their full cardioprotective effects Therefore, some recent studies have focused on enhancing the polyphenols' bioavailability, especially RES and curcumin, by employing nanoformulations, such as lipid-based nanoparticles liposomes , protein-based nanoformulations, polymers, micelles, and metal nanoparticles for drug delivery For instance, RES and curcumin co-delivery by polymeric micelles to doxorubicin-treated cardiomyocyte cell lines resulted in higher drug solubility and efficacy than non-polymeric forms and single-drug treatment Polymeric micelles used in these studies are biocompatible and FDA-approved.
Moreover, polymer-based drug delivery vehicles such as Poly D,L-lactic-co-glycolic acid PLGA nanoparticles demonstrated superior anti-atherosclerotic effects of curcumin-bioperine treatment compared to non-coated ones. Pillai et al. reported that curcumin-bioperine coated with PLGA nanoparticles significantly reduced ox-LDL levels, downregulating the atherosclerotic plaque-related gene expression in vitro The efficacy of PLGA-encapsulated curcumin was also illustrated in vivo in later studies, where gold-capped curcumin encapsulated within PLGA demonstrated enhanced solubility, bioavailability, and eventually, improved anti-hypertrophic characteristics in hypertrophic Wistar rat models Aside from polymeric-based drug delivery, extensive studies were carried out on the efficacy of liposome-targeted therapy — Liposomes are phospholipid-based nanocarriers designed for both hydrophilic and hydrophobic drug delivery.
Liposome preparation progress in recent years has introduced the ligand surface-engineered and long-circulating liposomes, allowing stability and sustained drug release in target tissues and enhanced bioavailability The use of liposomes in CVDs has become a promising candidate for future safe drug delivery without cytotoxicity.
RES-contained liposomes were demonstrated to enhance the respiratory capacity of the cardiomyocytes in vitro Moreover, the transplantation of mitochondrial-activated cardiac progenitor cells by liposomal RES into the heart of the mouse models with cardiomyopathy resulted in reduced oxidative stress and apoptotic activities of the cardiomyocytes Considering their minimal side effects and significant therapeutic features, polyphenols have introduced themselves as intriguing options for future HF treatment.
However, due to the low bioavailability and stability of polyphenols in the circulating system, limited clinical trials have been conducted evaluating their impact on human HF, and most of the studies are in vitro and in vivo animal models.
However, with recent advances in novel drug delivery systems, there is rising hope for translating nanoparticle delivery of these compounds to the clinical setting soon.
In conclusion, this study predominantly reviewed the therapeutic effects of polyphenol compounds and their underlying mechanisms in improving pathologic cardiac remodeling, leading to heart failure. Also, this study discusses the most recent advances and challenges in translating the antioxidative, anti-inflammatory, anti-apoptotic, and antifibrotic characteristics of these nutraceuticals into clinical settings.
The potential application of nano-drug delivery systems was also investigated regarding the limited solubility, stability, and bioavailability of the polyphenols in humans. Finally, further in-depth surveys are needed to understand better the involved molecular pathways of polyphenols in modulating cardiac remodeling and HF.
Also, there is a rising demand for viable strategies to better translate the in vitro and animal study results into the clinic. NH, AY, MS, YG, FA, RE, M-HA, MH, ZA, HM, MHJ, AM, and MR took part in creating the idea, design, and composing of the manuscript. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
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edu cardivascular cookies to personalize content, tailor ads Poljphenols improve the user experience. By using our Benefits of omega- fatty acids, you agree abd our collection of information Waist circumference and body fat the Benefits of omega- fatty acids of cookies. To learn more, view our Privacy Policy. edu no longer supports Internet Explorer. To browse Academia. edu and the wider internet faster and more securely, please take a few seconds to upgrade your browser. Epidemiological studies suggest that diets rich in polyphenols may be associated with reduced incidence of cardiovascular disorders mainly coronary heart disease and myocardial infarction. Citrus fruit for overall well-being Alessandro Antonelli Department of Clinical Polyphenosl Experimental Benefits of omega- fatty acids Laboratory of Primary Human Ans University of Pisa Hunger control during holidays Italy. ISSN Print : ISSN Online : cardiovasclar Page: [ - ] Pages: Polyphenos DOI: Background: Previous studies have shown that intake of polyphenols through the consumption of vegetables and fruits reduces the risk of Cardiovascular Disease CVD by potentially influencing endothelial cell function. Objective: In this review, the effects and molecular mechanisms of plant polyphenols, particularly resveratrol, epigallocatechin gallate EGCGand quercetin, on endothelial functions, and their putative protective effects against CVD are described.Video
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