• This record comes from PubMed

Dietary Polyphenols Targeting Arterial Stiffness: Interplay of Contributing Mechanisms and Gut Microbiome-Related Metabolism

. 2019 Mar 08 ; 11 (3) : . [epub] 20190308

Language English Country Switzerland Media electronic

Document type Journal Article, Review

Increased arterial stiffness is a degenerative vascular process, progressing with age that leads to a reduced capability of arteries to expand and contract in response to pressure changes. This progressive degeneration mainly affects the extracellular matrix of elastic arteries and causes loss of vascular elasticity. Recent studies point to significant interference of dietary polyphenols with mechanisms involved in the pathophysiology and progression of arterial stiffness. This review summarizes data from epidemiological and interventional studies on the effect of polyphenols on vascular stiffness as an illustration of current research and addresses possible etiological factors targeted by polyphenols, including pathways of vascular functionality, oxidative status, inflammation, glycation, and autophagy. Effects can either be inflicted directly by the dietary polyphenols or indirectly by metabolites originated from the host or microbial metabolic processes. The composition of the gut microbiome, therefore, determines the resulting metabolome and, as a consequence, the observed activity. On the other hand, polyphenols also influence the intestinal microbial composition, and therefore the metabolites available for interaction with relevant targets. As such, targeting the gut microbiome is another potential treatment option for arterial stiffness.

See more in PubMed

Hamilton P.K., Lockhart C.J., Quinn C.E., McVeigh G.E. Arterial stiffness: Clinical relevance, measurement and treatment. Clin. Sci. (Lond.) 2007;113:157–170. doi: 10.1042/CS20070080. PubMed DOI

Laurent S., Cockcroft J., Van Bortel L., Boutouyrie P., Giannattasio C., Hayoz D., Pannier B., Vlachopoulos C., Wilkinson I., Struijker-Boudier H., et al. Expert consensus document on arterial stiffness: Methodological issues and clinical applications. Eur. Heart J. 2006;27:2588–2605. doi: 10.1093/eurheartj/ehl254. PubMed DOI

Della Corte V., Tuttolomondo A., Pecoraro R., Di Raimondo D., Vassallo V., Pinto A. Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine. Curr. Pharm. Des. 2016;22:4658–4668. doi: 10.2174/1381612822666160510124801. PubMed DOI

Palombo C., Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul. Pharmacol. 2016;77:1–7. doi: 10.1016/j.vph.2015.11.083. PubMed DOI

Lyle A.N., Raaz U. Killing Me Unsoftly: Causes and Mechanisms of Arterial Stiffness. Arterioscler. Thromb. Vasc. Biol. 2017;37:e1–e11. doi: 10.1161/ATVBAHA.116.308563. PubMed DOI PMC

O’Rourke M.F., Hashimoto J. Mechanical factors in arterial aging: A clinical perspective. J. Am. Coll. Cardiol. 2007;50:1–13. doi: 10.1016/j.jacc.2006.12.050. PubMed DOI

Van Bortel L. Arterial stiffness: From surrogate marker to therapeutic target. Artery Res. 2016;14:10–14. doi: 10.1016/j.artres.2016.01.001. DOI

Cecelja M., Chowienczyk P. Molecular Mechanisms of Arterial Stiffening. Pulse. 2016;4:43–48. doi: 10.1159/000446399. PubMed DOI PMC

Quinn U., Tomlinson L.A., Cockcroft J.R. Arterial stiffness. JRSM Cardiovasc. Dis. 2012;1 doi: 10.1258/cvd.2012.012024. PubMed DOI PMC

Avolio A. Arterial Stiffness. Pulse. 2013;1:14–28. doi: 10.1159/000348620. PubMed DOI PMC

Sell D.R., Monnier V.M. Molecular Basis of Arterial Stiffening: Role of Glycation—A Mini-Review. Gerontology. 2012;58:227–237. doi: 10.1159/000334668. PubMed DOI

Smulyan H., Mookherjee S., Safar M.E. The two faces of hypertension: Role of aortic stiffness. J. Am. Soc. Hypertens. 2016;10:175–183. doi: 10.1016/j.jash.2015.11.012. PubMed DOI

Vlassopoulos A., Lean M.E.J., Combet E. Oxidative stress, protein glycation and nutrition—Interactions relevant to health and disease throughout the lifecycle. Proc. Nutr. Soc. 2014;73:430–438. doi: 10.1017/S0029665114000603. PubMed DOI

Papaioannou T.G., Karatzi K., Psaltopoulou T., Tousoulis D. Arterial ageing: Major nutritional and life-style effects. Ageing Res. Rev. 2017;37:162–163. doi: 10.1016/j.arr.2016.10.004. PubMed DOI

Lilamand M., Kelaiditi E., Guyonnet S., Antonelli Incalzi R., Raynaud-Simon A., Vellas B., Cesari M. Flavonoids and arterial stiffness: Promising perspectives. Nutr. Metab. Cardiovasc. Dis. 2014;24:698–704. doi: 10.1016/j.numecd.2014.01.015. PubMed DOI

Li P., Wang L., Liu C. Overweightness, obesity and arterial stiffness in healthy subjects: A systematic review and meta-analysis of literature studies. Postgrad. Med. 2017;129:224–230. doi: 10.1080/00325481.2017.1268903. PubMed DOI

Wu C.F., Liu P.Y., Wu T.J., Hung Y., Yang S.P., Lin G.M. Therapeutic modification of arterial stiffness: An update and comprehensive review. World J. Cardiol. 2015;7:742–753. doi: 10.4330/wjc.v7.i11.742. PubMed DOI PMC

Sasaki Y., Ikeda Y., Iwabayashi M., Akasaki Y., Ohishi M. The Impact of Autophagy on Cardiovascular Senescence and Diseases. Int. Heart J. 2017;58:666–673. doi: 10.1536/ihj.17-246. PubMed DOI

LaRocca T.J., Martens C.R., Seals D.R. Nutrition and other lifestyle influences on arterial aging. Ageing Res. Rev. 2017;39:106–119. doi: 10.1016/j.arr.2016.09.002. PubMed DOI PMC

Mozos I., Stoian D., Luca C.T. Crosstalk between Vitamins A, B12, D, K, C, and E Status and Arterial Stiffness. Dis. Markers. 2017 doi: 10.1155/2017/8784971. PubMed DOI PMC

Daiber A., Steven S., Weber A., Shuvaev V.V., Muzykantov V.R., Laher I., Li H., Lamas S., Münzel T. Targeting vascular (endothelial) dysfunction. Br. J. Pharmacol. 2017;174:1591–1619. doi: 10.1111/bph.13517. PubMed DOI PMC

Sharman J.E., Boutouyrie P., Laurent S. Arterial (Aortic) Stiffness in Patients with Resistant Hypertension: From Assessment to Treatment. Curr. Hypertens. Rep. 2017;19 doi: 10.1007/s11906-017-0704-7. PubMed DOI

Santilli F., D’Ardes D., Davi G. Oxidative stress in chronic vascular disease: From prediction to prevention. Vasc. Pharmacol. 2015;74:23–37. doi: 10.1016/j.vph.2015.09.003. PubMed DOI

Mozos I., Luca C.T. Crosstalk between Oxidative and Nitrosative Stress and Arterial Stiffness. Curr. Vasc. Pharmacol. 2017;15:446–456. doi: 10.2174/1570161115666170201115428. PubMed DOI

Mozos I., Malainer C., Horbanczuk J., Gug C., Stoian D., Luca C.T., Atanasov A.G. Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases. Front. Immunol. 2017;8:16. doi: 10.3389/fimmu.2017.01058. PubMed DOI PMC

Zanoli L., Rastelli S., Inserra G., Castellino P. Arterial structure and function in inflammatory bowel disease. World J. Gastroenterol. 2015;21:11304–11311. doi: 10.3748/wjg.v21.i40.11304. PubMed DOI PMC

De Meyer G.R.Y., Grootaert M.O.J., Michiels C.F., Kurdi A., Schrijvers D.M., Martinet W. Autophagy in Vascular Disease. Circ. Res. 2015;116:468–479. doi: 10.1161/CIRCRESAHA.116.303804. PubMed DOI

Perrotta I., Aquila S. The role of oxidative stress and autophagy in atherosclerosis. Oxid. Med. Cell. Longev. 2015;2015:130315. doi: 10.1155/2015/130315. PubMed DOI PMC

Fang C., Gu L., Smerin D., Mao S., Xiong X. The Interrelation between Reactive Oxygen Species and Autophagy in Neurological Disorders. Oxid. Med. Cell. Longev. 2017;2017:8495160. doi: 10.1155/2017/8495160. PubMed DOI PMC

Costa C., Tsatsakis A., Mamoulakis C., Teodoro M., Briguglio G., Caruso E., Tsoukalas D., Margina D., Dardiotis E., Kouretas D., et al. Current evidence on the effect of dietary polyphenols intake on chronic diseases. Food Chem. Toxicol. 2017;110:286–299. doi: 10.1016/j.fct.2017.10.023. PubMed DOI

Manach C., Scalbert A., Morand C., Remesy C., Jimenez L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr. 2004;79:727–747. doi: 10.1093/ajcn/79.5.727. PubMed DOI

Tresserra-Rimbau A., Rimm E.B., Medina-Remon A., Martinez-Gonzalez M.A., de la Torre R., Corella D., Salas-Salvado J., Gomez-Gracia E., Lapetra J., Aros F., et al. Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study. Nutr. Metab. Carbiovasc. Dis. 2014;24:639–647. doi: 10.1016/j.numecd.2013.12.014. PubMed DOI

Ludovici V., Barthelmes J., Nagele M.P., Enseleit F., Ferri C., Flammer A.J., Ruschitzka F., Sudano I. Cocoa, Blood Pressure, and Vascular Function. Front. Nutr. 2017;4:279–284. doi: 10.3389/fnut.2017.00036. PubMed DOI PMC

Rienks J., Barbaresko J., Nöthlings U. Association of Polyphenol Biomarkers with Cardiovascular Disease and Mortality Risk: A Systematic Review and Meta-Analysis of Observational Studies. Nutrients. 2017;9:415. doi: 10.3390/nu9040415. PubMed DOI PMC

Pinto P., Santos C.N. Worldwide (poly)phenol intake: Assessment methods and identified gaps. Eur. J. Nutr. 2017;56:1393–1408. doi: 10.1007/s00394-016-1354-2. PubMed DOI

Gil-Cardoso K., Gines I., Pinent M., Ardevol A., Blay M., Terra X. Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity. Nutr. Res. Rev. 2016;29:234–248. doi: 10.1017/S0954422416000159. PubMed DOI

Goszcz K., Duthie G.G., Stewart D., Leslie S.J., Megson I.L. Bioactive polyphenols and cardiovascular disease: Chemical antagonists, pharmacological agents or xenobiotics that drive an adaptive response? Br. J. Pharmacol. 2017;174:1209–1225. doi: 10.1111/bph.13708. PubMed DOI PMC

Zhang H., Tsao R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr. Opin. Food Sci. 2016;8:33–42. doi: 10.1016/j.cofs.2016.02.002. DOI

Milenkovic D., Morand C., Cassidy A., Konic-Ristic A., Tomas-Barberan F., Ordovas J.M., Kroon P., De Caterina R., Rodriguez-Mateos A. Interindividual Variability in Biomarkers of Cardiometabolic Health after Consumption of Major Plant-Food Bioactive Compounds and the Determinants Involved. Adv. Nutr. 2017;8:558–570. PubMed PMC

Menezes R., Rodriguez-Mateos A., Kaltsatou A., Gonzalez-Sarrias A., Greyling A., Giannaki C., Andres-Lacueva C., Milenkovic D., Gibney E.R., Dumont J., et al. Impact of Flavonols on Cardiometabolic Biomarkers: A Meta-Analysis of Randomized Controlled Human Trials to Explore the Role of Inter-Individual Variability. Nutrients. 2017;9 doi: 10.3390/nu9020117. DOI

Almeida A.F., Borge G.I.A., Piskula M., Tudose A., Tudoreanu L., Valentová K., Williamson G., Santos C.N. Bioavailability of Quercetin in Humans with a Focus on Interindividual Variation. Compr. Rev. Food Sci. Food Saf. 2018;17:714–731. doi: 10.1111/1541-4337.12342. PubMed DOI

Figueira I., Menezes R., Macedo D., Costa I., Dos Santos C.N. Polyphenols Beyond Barriers: A Glimpse into the Brain. Curr. Neuropharmacol. 2017;15:562–594. doi: 10.2174/1570159X14666161026151545. PubMed DOI PMC

Cardona F., Andres-Lacueva C., Tulipani S., Tinahones F.J., Queipo-Ortuno M.I. Benefits of polyphenols on gut microbiota and implications in human health. J. Nutr. Biochem. 2013;24:1415–1422. doi: 10.1016/j.jnutbio.2013.05.001. PubMed DOI

Griffiths L.A., Barrow A. Metabolism of flavonoid compounds in germ-free rats. Biochem. J. 1972;130:1161–1162. doi: 10.1042/bj1301161. PubMed DOI PMC

Valdes L., Cuervo A., Salazar N., Ruas-Madiedo P., Gueimonde M., Gonzalez S. The relationship between phenolic compounds from diet and microbiota: Impact on human health. Food Funct. 2015;6:2424–2439. doi: 10.1039/C5FO00322A. PubMed DOI

Singh R.K., Chang H.W., Yan D., Lee K.M., Ucmak D., Wong K., Abrouk M., Farahnik B., Nakamura M., Zhu T.H., et al. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 2017;15:17. doi: 10.1186/s12967-017-1175-y. PubMed DOI PMC

Sheflin A.M., Melby C.L., Carbonero F., Weir T.L. Linking dietary patterns with gut microbial composition and function. Gut Microbes. 2017;8:113–129. doi: 10.1080/19490976.2016.1270809. PubMed DOI PMC

Rowland I., Gibson G., Heinken A., Scott K., Swann J., Thiele I., Tuohy K. Gut microbiota functions: Metabolism of nutrients and other food components. Eur. J. Nutr. 2018;57:1–24. doi: 10.1007/s00394-017-1445-8. PubMed DOI PMC

Wiese S., Esatbeyoglu T., Winterhalter P., Kruse H.P., Winkler S., Bub A., Kulling S.E. Comparative biokinetics and metabolism of pure monomeric, dimeric, and polymeric flavan-3-ols: A randomized cross-over study in humans. Mol. Nutr. Food Res. 2015;59:610–621. doi: 10.1002/mnfr.201400422. PubMed DOI

Ottaviani J.I., Heiss C., Spencer J.P.E., Kelm M., Schroeter H. Recommending flavanols and procyanidins for cardiovascular health: Revisited. Mol. Asp. Med. 2018;61:63–75. doi: 10.1016/j.mam.2018.02.001. PubMed DOI

Trost K., Ulaszewska M.M., Stanstrup J., Albanese D., De Filippo C., Tuohy K.M., Natella F., Scaccini C., Mattivi F. Host: Microbiome co-metabolic processing of dietary polyphenols—An acute, single blinded, cross-over study with different doses of apple polyphenols in healthy subjects. Food Res. Int. 2018;112:108–128. doi: 10.1016/j.foodres.2018.06.016. PubMed DOI

Landete J.M., Arques J., Medina M., Gaya P., de Las Rivas B., Munoz R. Bioactivation of Phytoestrogens: Intestinal Bacteria and Health. Crit. Rev. Food Sci. Nutr. 2016;56:1826–1843. doi: 10.1080/10408398.2013.789823. PubMed DOI

Cai Y., Guo K., Chen C., Wang P., Zhang B., Zhou Q., Mei F., Su Y. Soya isoflavone consumption in relation to carotid intima-media thickness in Chinese equol excretors aged 40–65 years. Br. J. Nutr. 2012;108:1698–1704. doi: 10.1017/S0007114511007331. PubMed DOI

Hazim S., Curtis P.J., Schar M.Y., Ostertag L.M., Kay C.D., Minihane A.M., Cassidy A. Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: A double-blind randomized controlled trial. Am. J. Clin. Nutr. 2016;103:694–702. doi: 10.3945/ajcn.115.125690. PubMed DOI PMC

Clavel T., Desmarchelier C., Haller D., Gerard P., Rohn S., Lepage P., Daniel H. Intestinal microbiota in metabolic diseases: From bacterial community structure and functions to species of pathophysiological relevance. Gut Microbes. 2014;5:544–551. doi: 10.4161/gmic.29331. PubMed DOI

Braune A., Blaut M. Bacterial species involved in the conversion of dietary flavonoids in the human gut. Gut Microbes. 2016;7:216–234. doi: 10.1080/19490976.2016.1158395. PubMed DOI PMC

Karas D., Ulrichova J., Valentova K. Galloylation of polyphenols alters their biological activity. Food Chem. Toxicol. 2017;105:223–240. doi: 10.1016/j.fct.2017.04.021. PubMed DOI

Rodriguez-Mateos A., Cifuentes-Gomez T., Gonzalez-Salvador I., Ottaviani J.I., Schroeter H., Kelm M., Heiss C., Spencer J.P. Influence of age on the absorption, metabolism, and excretion of cocoa flavanols in healthy subjects. Mol. Nutr. Food Res. 2015;59:1504–1512. doi: 10.1002/mnfr.201500091. PubMed DOI

Tomas-Barberan F.A., Gonzalez-Sarrias A., Garcia-Villalba R., Nunez-Sanchez M.A., Selma M.V., Garcia-Conesa M.T., Espin J.C. Urolithins, the rescue of “old” metabolites to understand a “new” concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol. Nutr. Food Res. 2017;61 doi: 10.1002/mnfr.201500901. PubMed DOI

Espin J.C., Gonzalez-Sarrias A., Tomas-Barberan F.A. The gut microbiota: A key factor in the therapeutic effects of (poly) phenols. Biochem. Pharmacol. 2017;139:82–93. doi: 10.1016/j.bcp.2017.04.033. PubMed DOI

Cortes-Martin A., Garcia-Villalba R., Gonzalez-Sarrias A., Romo-Vaquero M., Loria-Kohen V., Ramirez-de-Molina A., Tomas-Barberan F.A., Selma M.V., Espin J.C. The gut microbiota urolithin metabotypes revisited: The human metabolism of ellagic acid is mainly determined by aging. Food Funct. 2018;9:4100–4106. doi: 10.1039/C8FO00956B. PubMed DOI

Sun Q., Wedick N.M., Pan A., Townsend M.K., Cassidy A., Franke A.A., Rimm E.B., Hu F.B., van Dam R.M. Gut microbiota metabolites of dietary lignans and risk of type 2 diabetes: A prospective investigation in two cohorts of U.S. women. Diabetes Care. 2014;37:1287–1295. doi: 10.2337/dc13-2513. PubMed DOI PMC

Vanharanta M., Voutilainen S., Rissanen T.H., Adlercreutz H., Salonen J.T. Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study. Arch. Intern. Med. 2003;163:1099–1104. doi: 10.1001/archinte.163.9.1099. PubMed DOI

van der Schouw Y.T., Pijpe A., Lebrun C.E., Bots M.L., Peeters P.H., van Staveren W.A., Lamberts S.W., Grobbee D.E. Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women. Arterioscler. Thromb. Vasc. Biol. 2002;22:1316–1322. doi: 10.1161/01.ATV.0000027176.83618.1A. PubMed DOI

Morling J.R., Yeoh S.E., Kolbach D.N. Rutosides for treatment of post-thrombotic syndrome. Cochrane Database Syst. Rev. 2015;4:CD005625. doi: 10.1002/14651858.CD005625.pub3. PubMed DOI

Martinez-Zapata M.J., Vernooij R.W., Uriona Tuma S.M., Stein A.T., Moreno R.M., Vargas E., Capella D., Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst. Rev. 2016;4:CD003229. doi: 10.1002/14651858.CD003229.pub3. PubMed DOI PMC

Williamson G., Clifford M.N. Colonic metabolites of berry polyphenols: The missing link to biological activity? Br. J. Nutr. 2010;104(Suppl. 3):S48–S66. doi: 10.1017/S0007114510003946. PubMed DOI

Amaretti A., Raimondi S., Leonardi A., Quartieri A., Rossi M. Hydrolysis of the rutinose-conjugates flavonoids rutin and hesperidin by the gut microbiota and bifidobacteria. Nutrients. 2015;7:2788–2800. doi: 10.3390/nu7042788. PubMed DOI PMC

Slamova K., Kapesova J., Valentova K. “Sweet Flavonoids”: Glycosidase-Catalyzed Modifications. Int. J. Mol. Sci. 2018;19 doi: 10.3390/ijms19072126. PubMed DOI PMC

Najmanova I., Pourova J., Voprsalova M., Pilarova V., Semecky V., Novakova L., Mladenka P. Flavonoid metabolite 3-(3-hydroxyphenyl)propionic acid formed by human microflora decreases arterial blood pressure in rats. Mol. Nutr. Food Res. 2016;60:981–991. doi: 10.1002/mnfr.201500761. PubMed DOI

Pourova J., Najmanova I., Voprsalova M., Migkos T., Pilarova V., Applova L., Novakova L., Mladenka P. Two flavonoid metabolites, 3,4-dihydroxyphenylacetic acid and 4-methylcatechol, relax arteries ex vivo and decrease blood pressure in vivo. Vascul. Pharmacol. 2018;111:36–43. doi: 10.1016/j.vph.2018.08.008. PubMed DOI

Khan N., Khymenets O., Urpi-Sarda M., Tulipani S., Garcia-Aloy M., Monagas M., Mora-Cubillos X., Llorach R., Andres-Lacueva C. Cocoa Polyphenols and Inflammatory Markers of Cardiovascular Disease. Nutrients. 2014;6:844–880. doi: 10.3390/nu6020844. PubMed DOI PMC

Jang S., Sun J.H., Chen P., Lakshman S., Molokin A., Harnly J.M., Vinyard B.T., Urban J.F., Davis C.D., Solano-Aguilar G. Flavanol-Enriched Cocoa Powder Alters the Intestinal Microbiota, Tissue and Fluid Metabolite Profiles, and Intestinal Gene Expression in Pigs. J. Nutr. 2016;146:673–680. doi: 10.3945/jn.115.222968. PubMed DOI PMC

Massot-Cladera M., Perez-Berezo T., Franch A., Castell M., Perez-Cano F.J. Cocoa modulatory effect on rat faecal microbiota and colonic crosstalk. Arch. Biochem. Biophys. 2012;527:105–112. doi: 10.1016/j.abb.2012.05.015. PubMed DOI

Seo K.H., Kim D.H., Jeong D., Yokoyama W., Kim H. Chardonnay grape seed flour supplemented diets alter intestinal microbiota in diet-induced obese mice. J. Food Biochem. 2017;41:9. doi: 10.1111/jfbc.12396. DOI

Chacar S., Itani T., Hajal J., Saliba Y., Louka N., Faivre J.F., Maroun R., Fares N. The Impact of Long-Term Intake of Phenolic Compounds-Rich Grape Pomace on Rat Gut Microbiota. J. Food Sci. 2018;83:246–251. doi: 10.1111/1750-3841.14006. PubMed DOI

Nash V., Ranadheera C.S., Georgousopoulou E.N., Mellor D.D., Panagiotakos D.B., McKune A.J., Kellett J., Naumovski N. The effects of grape and red wine polyphenols on gut microbiota—A systematic review. Food Res. Int. 2018;113:277–287. doi: 10.1016/j.foodres.2018.07.019. PubMed DOI

Cueva C., Gil-Sanchez I., Ayuda-Duran B., Gonzalez-Manzano S., Gonzalez-Paramas A.M., Santos-Buelga C., Bartolome B., Moreno-Arribas M.V. An Integrated View of the Effects of Wine Polyphenols and Their Relevant Metabolites on Gut and Host Health. Molecules. 2017;22:15. doi: 10.3390/molecules22010099. PubMed DOI PMC

Yuan X.J., Long Y., Ji Z.H., Gao J., Fu T., Yan M., Zhang L., Su H.X., Zhang W.L., Wen X.H., et al. Green Tea Liquid Consumption Alters the Human Intestinal and Oral Microbiome. Mol. Nutr. Food Res. 2018;62:15. doi: 10.1002/mnfr.201800178. PubMed DOI PMC

Cheng M., Zhang X., Miao Y.J., Cao J.X., Wu Z.F., Weng P.F. The modulatory effect of (−)-epigallocatechin 3-O-(3-O-methyl) gallate (EGCG3″Me) on intestinal microbiota of high fat diet-induced obesity mice model. Food Res. Int. 2017;92:9–16. doi: 10.1016/j.foodres.2016.12.008. PubMed DOI

Pavlidou E., Giaginis C., Fasoulas A., Petridis D. Clinical Evaluation of the Effect of Blueberries Consumption on Chronic Diseases, Illness Prevention and Health Promotion. Nat. Prod. J. 2018;8:45–53. doi: 10.2174/2210315507666170830120953. DOI

Prieto I., Hidalgo M., Segarra A.B., Martinez-Rodriguez A.M., Cobo A., Ramirez M., Abriouel H., Galvez A., Martinez-Canamero M. Influence of a diet enriched with virgin olive oil or butter on mouse gut microbiota and its correlation to physiological and biochemical parameters related to metabolic syndrome. PLoS ONE. 2018;13:20. doi: 10.1371/journal.pone.0190368. PubMed DOI PMC

Tomas-Barberan F.A., Selma M.V., Espin J.C. Interactions of gut microbiota with dietary polyphenols and consequences to human health. Curr. Opin. Clin. Nutr. Metab. Care. 2016;19:471–476. doi: 10.1097/MCO.0000000000000314. PubMed DOI

Stevens J.F., Maier C.S. The chemistry of gut microbial metabolism of polyphenols. Phytochem. Rev. 2016;15:425–444. doi: 10.1007/s11101-016-9459-z. PubMed DOI PMC

Janeiro M.H., Ramirez M.J., Milagro F.I., Martinez J.A., Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients. 2018;10:1398. doi: 10.3390/nu10101398. PubMed DOI PMC

Velasquez M.T., Ramezani A., Manal A., Raj D.S. Trimethylamine N-Oxide: The Good, the Bad and the Unknown. Toxins. 2016;8:11. doi: 10.3390/toxins8110326. PubMed DOI PMC

Li T.J., Chen Y.L., Gua C.J., Li X.D. Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress. Front. Physiol. 2017;8:350. doi: 10.3389/fphys.2017.00350. PubMed DOI PMC

Lyu M., Wang Y.F., Fan G.W., Wang X.Y., Xu S.Y., Zhu Y. Balancing Herbal Medicine and Functional Food for Prevention and Treatment of Cardiometabolic Diseases through Modulating Gut Microbiota. Front. Microbiol. 2017;8:21. doi: 10.3389/fmicb.2017.02146. PubMed DOI PMC

Battson M.L., Lee D.M., Jarrell D.K., Hou S., Ecton K.E., Weir T.L., Gentile C.L. Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction. Am. J. Physiol. Endocrinol. Metab. 2018;314:E468–E477. doi: 10.1152/ajpendo.00187.2017. PubMed DOI PMC

Chen M.L., Yi L., Zhang Y., Zhou X., Ran L., Yang J.N., Zhu J.D., Zhang Q.Y., Mi M.T. Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota. mBio. 2016;7:14. doi: 10.1128/mBio.02210-15. PubMed DOI PMC

Bresciani L., Dall’Asta M., Favari C., Calani L., Del Rio D., Brighenti F. An in vitro exploratory study of dietary strategies based on polyphenol-rich beverages, fruit juices and oils to control trimethylamine production in the colon. Food Funct. 2018;9:6470–6483. doi: 10.1039/C8FO01778F. PubMed DOI

Menni C., Lin C.H., Cecelja M., Mangino M., Matey-Hernandez M.L., Keehn L., Mohney R.P., Steves C.J., Spector T.D., Kuo C.F., et al. Gut microbial diversity is associated with lower arterial stiffness in women. Eur. Heart J. 2018;39:2390–2397. doi: 10.1093/eurheartj/ehy226. PubMed DOI PMC

Laurent S., Bruno R.M. Gut microbiome composition, a third player in the inflammation–arterial stiffness relationship. Eur. Heart J. 2018;39:2398–2400. doi: 10.1093/eurheartj/ehy300. PubMed DOI

Cross T.W.L., Zidon T.M., Welly R.J., Park Y.M., Britton S.L., Koch L.G., Rottinghaus G.E., de Godoy M.R.C., Padilla J., Swanson K.S., et al. Soy Improves Cardiometabolic Health and Cecal Microbiota in Female Low-Fit Rats. Sci. Rep. 2017;7:15. doi: 10.1038/s41598-017-08965-0. PubMed DOI PMC

Sies H., Hollman P.C.H., Grune T., Stahl W., Biesalski H.K., Williamson G. Protection by Flavanol-Rich Foods Against Vascular Dysfunction and Oxidative Damage: 27th Hohenheim Consensus Conference. Adv. Nutr. 2012;3:217–221. doi: 10.3945/an.111.001578. PubMed DOI PMC

Feliciano R.P., Istas G., Heiss C., Rodriguez-Mateos A. Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry. Molecules. 2016;21:15. doi: 10.3390/molecules21091120. PubMed DOI PMC

Mansuri M.L., Parihar P., Solanki I., Parihar M.S. Flavonoids in modulation of cell survival signalling pathways. Genes Nutr. 2014;9 doi: 10.1007/s12263-014-0400-z. PubMed DOI PMC

Wang J.N., Guo Z.H., Fu Y.X., Wu Z.Y., Huang C., Zheng C.L., Shar P.A., Wang Z.Z., Xiao W., Wang Y.H. Weak-binding molecules are not drugs?-toward a systematic strategy for finding effective weak-binding drugs. Brief. Bioinform. 2017;18:321–332. doi: 10.1093/bib/bbw018. PubMed DOI

Ottaviani J.I., Fong R., Kimball J., Ensunsa J.L., Britten A., Lucarelli D., Luben R., Grace P.B., Mawson D.H., Tym A., et al. Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies. Sci. Rep. 2018;8:11. doi: 10.1038/s41598-018-28333-w. PubMed DOI PMC

Jennings A., Welch A.A., Fairweather-Tait S.J., Kay C., Minihane A.M., Chowienczyk P., Jiang B.Y., Cecelja M., Spector T., Macgregor A., et al. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women. Am. J. Clin. Nutr. 2012;96:781–788. doi: 10.3945/ajcn.112.042036. PubMed DOI

Vlachopoulos C.V., Alexopoulos N.A., Aznaouridis K.A., Ioakeimidis N.C., Dima I.A., Dagre A., Vasiliadou C., Stefanadi E.C., Stefanadis C.I. Relation of habitual cocoa consumption to aortic stiffness and wave reflections, and to central hemodynamics in healthy individuals. Am. J. Cardiol. 2007;99:1473–1475. doi: 10.1016/j.amjcard.2006.12.081. PubMed DOI

Upadhyay S., Dixit M. Role of Polyphenols and Other Phytochemicals on Molecular Signaling. Oxid. Med. Cell. Longev. 2015;2015:504253. doi: 10.1155/2015/504253. PubMed DOI PMC

Vlachopoulos C., Alexopoulos N., Stefanadis C. Effects of nutrition on arterial rigidity and reflected waves. Sang. Thromb. Vaiss. 2007;19:479–486.

Arranz S., Valderas-Martinez P., Chiva-Blanch G., Casas R., Urpi-Sarda M., Lamuela-Raventos R.M., Estruch R. Cardioprotective effects of cocoa: Clinical evidence from randomized clinical intervention trials in humans. Mol. Nutr. Food. Res. 2013;57:936–947. doi: 10.1002/mnfr.201200595. PubMed DOI

Sansone R., Ottaviani J.I., Rodriguez-Mateos A., Heinen Y., Noske D., Spencer J.P., Crozier A., Merx M.W., Kelm M., Schroeter H., et al. Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: Randomized, double-masked controlled studies. Am. J. Clin. Nutr. 2017;105:352–360. doi: 10.3945/ajcn.116.140046. PubMed DOI

Macready A.L., George T.W., Chong M.F., Alimbetov D.S., Jin Y., Vidal A., Spencer J.P., Kennedy O.B., Tuohy K.M., Minihane A.M., et al. Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease—FLAVURS: A randomized controlled trial. Am. J. Clin. Nutr. 2014;99:479–489. doi: 10.3945/ajcn.113.074237. PubMed DOI

Grassi D., Draijer R., Desideri G., Mulder T., Ferri C. Black Tea Lowers Blood Pressure and Wave Reflections in Fasted and Postprandial Conditions in Hypertensive Patients: A Randomised Study. Nutrients. 2015;7:1037–1051. doi: 10.3390/nu7021037. PubMed DOI PMC

Ray S., Miglio C., Eden T., Del Rio D. Assessment of vascular and endothelial dysfunction in nutritional studies. Nutr. Metab. Carbiovasc. Dis. 2014;24:940–946. doi: 10.1016/j.numecd.2014.03.011. PubMed DOI

Vendrame S., Del Bo C., Ciappellano S., Riso P., Klimis-Zacas D. Berry Fruit Consumption and Metabolic Syndrome. Antioxidants. 2016;5:34. doi: 10.3390/antiox5040034. PubMed DOI PMC

Rodriguez-Mateos A., Heiss C., Borges G., Crozier A. Berry (poly)phenols and cardiovascular health. J. Agric. Food Chem. 2014;62:3842–3851. doi: 10.1021/jf403757g. PubMed DOI

Blumberg J.B., Vita J.A., Chen C.Y.O. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships. Nutrients. 2015;7:10032–10052. doi: 10.3390/nu7125519. PubMed DOI PMC

Pase M.P., Grima N.A., Sarris J. The effects of dietary and nutrient interventions on arterial stiffness: A systematic review. Am. J. Clin. Nutr. 2011;93:446–454. doi: 10.3945/ajcn.110.002725. PubMed DOI

Nestel P., Fujii A., Zhang L. An isoflavone metabolite reduces arterial stiffness and blood pressure in overweight men and postmenopausal women. Atherosclerosis. 2007;192:184–189. doi: 10.1016/j.atherosclerosis.2006.04.033. PubMed DOI

Vlachopoulos C., Aznaouridis K., Alexopoulos N., Economou E., Andreadou I., Stefanadis C. Effect of dark chocolate on arterial function in healthy individuals. Am. J. Hypertens. 2005;18:785–791. doi: 10.1016/j.amjhyper.2004.12.008. PubMed DOI

Grassi D., Desideri G., Necozione S., di Giosia P., Barnabei R., Allegaert L., Bernaert H., Ferri C. Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals. J. Hypertens. 2015;33:294–303. doi: 10.1097/HJH.0000000000000412. PubMed DOI

Grassi D., Desideri G., Necozione S., Ruggieri F., Blumberg J.B., Stornello M., Ferri C. Protective effects of flavanol-rich dark chocolate on endothelial function and wave reflection during acute hyperglycemia. Hypertension. 2012;60:827–832. doi: 10.1161/HYPERTENSIONAHA.112.193995. PubMed DOI

Grassi D., Desideri G., Necozione S., Lippi C., Casale R., Properzi G., Blumberg J.B., Ferri C. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J. Nutr. 2008;138:1671–1676. doi: 10.1093/jn/138.9.1671. PubMed DOI

Grassi D., Socci V., Tempesta D., Ferri C., De Gennaro L., Desideri G., Ferrara M. Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals. J. Hypertens. 2016;34:1298–1308. doi: 10.1097/HJH.0000000000000926. PubMed DOI

Heiss C., Sansone R., Karimi H., Krabbe M., Schuler D., Rodriguez-Mateos A., Kraemer T., Cortese-Krott M.M., Kuhnle G.G., Spencer J.P., et al. Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: A randomized, controlled, double-masked trial. Age. 2015;37:9794. doi: 10.1007/s11357-015-9794-9. PubMed DOI PMC

Basu A., Betts N.M., Leyva M.J., Fu D., Aston C.E., Lyons T.J. Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast. J. Nutr. 2015;145:2325–2332. doi: 10.3945/jn.115.215772. PubMed DOI PMC

West S.G., McIntyre M.D., Piotrowski M.J., Poupin N., Miller D.L., Preston A.G., Wagner P., Groves L.F., Skulas-Ray A.C. Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults. Br. J. Nutr. 2014;111:653–661. doi: 10.1017/S0007114513002912. PubMed DOI

Dower J.I., Geleijnse J.M., Gijsbers L., Zock P.L., Kromhout D., Hollman P.C. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: A randomized, double-blind, placebo-controlled, crossover trial. Am. J. Clin. Nutr. 2015;101:914–921. doi: 10.3945/ajcn.114.098590. PubMed DOI

Dower J.I., Geleijnse J.M., Kroon P.A., Philo M., Mensink M., Kromhout D., Hollman P.C. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study. Mol. Nutr. Food Res. 2016;60:2379–2386. doi: 10.1002/mnfr.201600045. PubMed DOI

Ward N.C., Hodgson J.M., Woodman R.J., Zimmermann D., Poquet L., Leveques A., Actis-Goretta L., Puddey I.B., Croft K.D. Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women. Food Funct. 2016;7:2197–2203. doi: 10.1039/C6FO00248J. PubMed DOI

Jokura H., Watanabe I., Umeda M., Hase T., Shimotoyodome A. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults. Nutr. Res. 2015;35:873–881. doi: 10.1016/j.nutres.2015.07.005. PubMed DOI

Grassi D., Mulder T.P., Draijer R., Desideri G., Molhuizen H.O., Ferri C. Black tea consumption dose-dependently improves flow-mediated dilation in healthy males. J. Hypertens. 2009;27:774–781. doi: 10.1097/HJH.0b013e328326066c. PubMed DOI

Ryu O.H., Lee J., Lee K.W., Kim H.Y., Seo J.A., Kim S.G., Kim N.H., Baik S.H., Choi D.S., Choi K.M. Effects of green tea consumption on inflammation, insulin resistance and pulse wave velocity in type 2 diabetes patients. Diabetes Res. Clin. Pract. 2006;71:356–358. doi: 10.1016/j.diabres.2005.08.001. PubMed DOI

Miller R.J., Jackson K.G., Dadd T., Mayes A.E., Brown A.L., Minihane A.M. The impact of the catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract. Br. J. Nutr. 2011;105:1138–1144. doi: 10.1017/S0007114510004836. PubMed DOI

Bondonno N.P., Bondonno C.P., Blekkenhorst L.C., Considine M.J., Maghzal G., Stocker R., Woodman R.J., Ward N.C., Hodgson J.M., Croft K.D. Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomised Controlled Clinical Trial. Mol. Nutr. Food Res. 2018;62 doi: 10.1002/mnfr.201700674. PubMed DOI

Cerletti C., Gianfagna F., Tamburrelli C., De Curtis A., D’Imperio M., Coletta W., Giordano L., Lorenzet R., Rapisarda P., Reforgiato Recupero G., et al. Orange juice intake during a fatty meal consumption reduces the postprandial low-grade inflammatory response in healthy subjects. Thromb. Res. 2015;135:255–259. doi: 10.1016/j.thromres.2014.11.038. PubMed DOI

Habauzit V., Verny M.A., Milenkovic D., Barber-Chamoux N., Mazur A., Dubray C., Morand C. Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: A randomized, controlled, crossover trial. Am. J. Clin. Nutr. 2015;102:66–74. doi: 10.3945/ajcn.114.104646. PubMed DOI

Schaer M.Y., Curtis P.J., Hazim S., Ostertag L.M., Kay C.D., Potter J.F., Cassidy A. Orange juice-derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: A randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease. Am. J. Clin. Nutr. 2015;101:931–938. doi: 10.3945/ajcn.114.104364. PubMed DOI PMC

Mathew A.S., Capel-Williams G.M., Berry S.E., Hall W.L. Acute effects of pomegranate extract on postprandial lipaemia, vascular function and blood pressure. Plant Foods Hum. Nutr. 2012;67:351–357. doi: 10.1007/s11130-012-0318-9. PubMed DOI

Lynn A., Hamadeh H., Leung W.C., Russell J.M., Barker M.E. Effects of Pomegranate Juice Supplementation on Pulse Wave Velocity and Blood Pressure in Healthy Young and Middle-aged Men and Women. Plant Foods Hum. Nutr. 2012;67:309–314. doi: 10.1007/s11130-012-0295-z. PubMed DOI

Gerstgrasser A., Rochter S., Dressler D., Schon C., Reule C., Buchwald-Werner S. In vitro Activation of eNOS by Mangifera indica (Careless (TM)) and Determination of an Effective Dosage in a Randomized, Double-Blind, Human Pilot Study on Microcirculation. Planta Med. 2016;82:298–304. doi: 10.1055/s-0035-1558219. PubMed DOI

Ruel G., Lapointe A., Pomerleau S., Couture P., Lemieux S., Lamarche B., Couillard C. Evidence that cranberry juice may improve augmentation index in overweight men. Nutr. Res. 2013;33:41–49. doi: 10.1016/j.nutres.2012.11.002. PubMed DOI

Dohadwala M.M., Holbrook M., Hamburg N.M., Shenouda S.M., Chung W.B., Titas M., Kluge M.A., Wang N., Palmisano J., Milbury P.E., et al. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease. Am. J. Clin. Nutr. 2011;93:934–940. doi: 10.3945/ajcn.110.004242. PubMed DOI PMC

Del Bo C., Porrini M., Fracassetti D., Campolo J., Klimis-Zacas D., Riso P. A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: A randomized-controlled trial. Food Funct. 2014;5:3107–3116. doi: 10.1039/C4FO00570H. PubMed DOI

Del Bo C., Porrini M., Campolo J., Parolini M., Lanti C., Klimis-Zacas D., Riso P. A single blueberry (Vaccinium corymbosum) portion does not affect markers of antioxidant defence and oxidative stress in healthy volunteers following cigarette smoking. Mutagenesis. 2016;31:215–224. doi: 10.1093/mutage/gev079. PubMed DOI

Del Bo C., Deon V., Campolo J., Lanti C., Parolini M., Porrini M., Klimis-Zacas D., Riso P. A serving of blueberry (V. corymbosum) acutely improves peripheral arterial dysfunction in young smokers and non-smokers: Two randomized, controlled, crossover pilot studies. Food Funct. 2017;8:4108–4117. doi: 10.1039/C7FO00861A. PubMed DOI

Johnson S.A., Figueroa A., Navaei N., Wong A., Kalfon R., Ormsbee L.T., Feresin R.G., Elam M.L., Hooshmand S., Payton M.E., et al. Daily Blueberry Consumption Improves Blood Pressure and Arterial Stiffness in Postmenopausal Women with Pre- and Stage 1-Hypertension: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J. Acad. Nutr. Diet. 2015;115:369–377. doi: 10.1016/j.jand.2014.11.001. PubMed DOI

Richter C.K., Skulas-Ray A.C., Gaugler T.L., Lambert J.D., Proctor D.N., Kris-Etherton P.M. Incorporating freeze-dried strawberry powder into a high-fat meal does not alter postprandial vascular function or blood markers of cardiovascular disease risk: A randomized controlled trial. Am. J. Clin. Nutr. 2017;105:313–322. doi: 10.3945/ajcn.116.141804. PubMed DOI PMC

Castro-Acosta M.L., Smith L., Miller R.J., McCarthy D.I., Farrimond J.A., Hall W.L. Drinks containing anthocyanin-rich blackcurrant extract decrease postprandial blood glucose, insulin and incretin concentrations. J. Nutr. Biochem. 2016;38:154–161. doi: 10.1016/j.jnutbio.2016.09.002. PubMed DOI PMC

Jeong H.S., Hong S.J., Lee T.B., Kwon J.W., Jeong J.T., Joo H.J., Park J.H., Ahn C.M., Yu C.W., Lim D.S. Effects of Black Raspberry on Lipid Profiles and Vascular Endothelial Function in Patients with Metabolic Syndrome. Phytother. Res. 2014;28:1492–1498. doi: 10.1002/ptr.5154. PubMed DOI

Jeong H.S., Kim S., Hong S.J., Choi S.C., Choi J.H., Kim J.H., Park C.Y., Cho J.Y., Lee T.B., Kwon J.W., et al. Black Raspberry Extract Increased Circulating Endothelial Progenitor Cells and Improved Arterial Stiffness in Patients with Metabolic Syndrome: A Randomized Controlled Trial. J. Med. Food. 2016;19:346–352. doi: 10.1089/jmf.2015.3563. PubMed DOI

Siasos G., Tousoulis D., Kokkou E., Oikonomou E., Kollia M.E., Verveniotis A., Gouliopoulos N., Zisimos K., Plastiras A., Maniatis K., et al. Favorable Effects of Concord Grape Juice on Endothelial Function and Arterial Stiffness in Healthy Smokers. Am. J. Hypertens. 2014;27:38–45. doi: 10.1093/ajh/hpt176. PubMed DOI

Park E., Edirisinghe I., Choy Y.Y., Waterhouse A., Burton-Freeman B. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: A randomised, double-blinded, two-arm, parallel, placebo-controlled trial. Br. J. Nutr. 2016;115:226–238. doi: 10.1017/S0007114515004328. PubMed DOI

Draijer R., de Graaf Y., Slettenaar M., de Groot E., Wright C.I. Consumption of a polyphenol-rich grape-wine extract lowers ambulatory blood pressure in mildly hypertensive subjects. Nutrients. 2015;7:3138–3153. doi: 10.3390/nu7053138. PubMed DOI PMC

Naissides M., Pal S., Mamo J.C., James A.P., Dhaliwal S. The effect of chronic consumption of red wine polyphenols on vascular function in postmenopausal women. Eur. J. Clin. Nutr. 2006;60:740–745. doi: 10.1038/sj.ejcn.1602377. PubMed DOI

Imamura H., Yamaguchi T., Nagayama D., Saiki A., Shirai K., Tatsuno I. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients with Type 2 Diabetes Mellitus. Int. Heart J. 2017;58:577–583. doi: 10.1536/ihj.16-373. PubMed DOI

Wong R.H.X., Howe P.R.C., Buckley J.D., Coates A.M., Kunz I., Berry N.M. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr. Metab. Carbiovasc. Dis. 2011;21:851–856. doi: 10.1016/j.numecd.2010.03.003. PubMed DOI

Wong R.H.X., Berry N.M., Coates A.M., Buckley J.D., Bryan J., Kunz I., Howe P.R.C. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J. Hypertens. 2013;31:1819–1827. doi: 10.1097/HJH.0b013e328362b9d6. PubMed DOI

Teede H.J., McGrath B.P., DeSilva L., Cehun M., Fassoulakis A., Nestel P.J. Isoflavones reduce arterial stiffness: A placebo-controlled study in men and postmenopausal women. Arterioscler. Thromb. Vasc. Biol. 2003;23:1066–1071. doi: 10.1161/01.ATV.0000072967.97296.4A. PubMed DOI

Hoshida S., Miki T., Nakagawa T., Shinoda Y., Inoshiro N., Terada K., Adachi T. Different effects of isoflavones on vascular function in premenopausal and postmenopausal smokers and nonsmokers: NYMPH study. Heart Vessels. 2011;26:590–595. doi: 10.1007/s00380-010-0103-3. PubMed DOI

Richter C.K., Skulas-Ray A.C., Fleming J.A., Link C.J., Mukherjea R., Krul E.S., Kris-Etherton P.M. Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: A dose-response randomised controlled trial. Br. J. Nutr. 2017;117:1403–1413. doi: 10.1017/S000711451700143X. PubMed DOI PMC

Curtis P.J., Potter J., Kroon P.A., Wilson P., Dhatariya K., Sampson M., Cassidy A. Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: A double-blind randomized controlled trial. Am. J. Clin. Nutr. 2013;97:936–942. doi: 10.3945/ajcn.112.043745. PubMed DOI

Clerici C., Setchell K.D., Battezzati P.M., Pirro M., Giuliano V., Asciutti S., Castellani D., Nardi E., Sabatino G., Orlandi S., et al. Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk. J. Nutr. 2007;137:2270–2278. doi: 10.1093/jn/137.10.2270. PubMed DOI

Clerici C., Nardi E., Battezzati P.M., Asciutti S., Castellani D., Corazzi N., Giuliano V., Gizzi S., Perriello G., Di Matteo G., et al. Novel soy germ pasta improves endothelial function, blood pressure, and oxidative stress in patients with type 2 diabetes. Diabetes Care. 2011;34:1946–1948. doi: 10.2337/dc11-0495. PubMed DOI PMC

Reverri E.J., LaSalle C.D., Franke A.A., Steinberg F.M. Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk. Mol. Nutr. Food Res. 2015;59:323–333. doi: 10.1002/mnfr.201400270. PubMed DOI PMC

Lockyer S., Corona G., Yaqoob P., Spencer J.P., Rowland I. Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: A randomised, double-blind, placebo-controlled, cross-over trial. Br. J. Nutr. 2015;114:75–83. doi: 10.1017/S0007114515001269. PubMed DOI

Verhoeven V., Van der Auwera A., Van Gaal L., Remmen R., Apers S., Stalpaert M., Wens J., Hermans N. Can red yeast rice and olive extract improve lipid profile and cardiovascular risk in metabolic syndrome?: A double blind, placebo controlled randomized trial. BMC Complement. Altern. Med. 2015;15:8. doi: 10.1186/s12906-015-0576-9. PubMed DOI PMC

Hermans N., Van der Auwera A., Breynaert A., Verlaet A., De Bruyne T., Van Gaal L., Pieters L., Verhoeven V. A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, OxLDL and Lp-PLA(2), in subjects with metabolic syndrome: A randomised, double-blind, placebo-controlled trial. Trials. 2017;18:8. doi: 10.1186/s13063-017-2058-5. PubMed DOI PMC

Pais P., Rull S., Villar A. Impact of a proprietary standardized olive fruit extract (Proliva (R)) on CAVI assessments in subjects with arterial stiffness risk. Planta Med. 2016;82:2. doi: 10.1055/s-0036-1596929. PubMed DOI PMC

Mullan A., Delles C., Ferrell W., Mullen W., Edwards C.A., McColl J.H., Roberts S.A., Lean M.E., Sattar N. Effects of a beverage rich in (poly)phenols on established and novel risk markers for vascular disease in medically uncomplicated overweight or obese subjects: A four week randomized placebo-controlled trial. Atherosclerosis. 2016;246:169–176. doi: 10.1016/j.atherosclerosis.2016.01.004. PubMed DOI

Chuengsamarn S., Rattanamongkolgul S., Phonrat B., Tungtrongchitr R., Jirawatnotai S. Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: A randomized controlled trial. J. Nutr. Biochem. 2014;25:144–150. doi: 10.1016/j.jnutbio.2013.09.013. PubMed DOI

Akazawa N., Choi Y., Miyaki A., Tanabe Y., Sugawara J., Ajisaka R., Maeda S. Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women. Nutr. Res. 2012;32:795–799. doi: 10.1016/j.nutres.2012.09.002. PubMed DOI

Katz D.L., Davidhi A., Ma Y.Y., Kavak Y., Bifulco L., Njike V.Y. Effects of Walnuts on Endothelial Function in Overweight Adults with Visceral Obesity: A Randomized, Controlled, Crossover Trial. J. Am. Coll. Nutr. 2012;31:415–423. doi: 10.1080/07315724.2012.10720468. PubMed DOI PMC

Bruell V., Burak C., Stoffel-Wagner B., Wolffram S., Nickenig G., Mueller C., Langguth P., Alteheld B., Fimmers R., Naaf S., et al. Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-) hypertension: A randomised double-blinded placebo-controlled cross-over trial. Br. J. Nutr. 2015;114:1263–1277. doi: 10.1017/S0007114515002950. PubMed DOI PMC

Yui S., Fujiwara S., Harada K., Motoike-Hamura M., Sakai M., Matsubara S., Miyazaki K. Beneficial Effects of Lemon Balm Leaf Extract on In Vitro Glycation of Proteins, Arterial Stiffness, and Skin Elasticity in Healthy Adults. J. Nutr. Sci. Vitaminol. 2017;63:59–68. doi: 10.3177/jnsv.63.59. PubMed DOI

Siti H.N., Kamisah Y., Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review) Vasc. Pharmacol. 2015;71:40–56. doi: 10.1016/j.vph.2015.03.005. PubMed DOI

Katz D.L., Doughty K., Ali A. Cocoa and Chocolate in Human Health and Disease. Antioxid. Redox Signal. 2011;15:2779–2811. doi: 10.1089/ars.2010.3697. PubMed DOI PMC

Croft K.D. Dietary polyphenols: Antioxidants or not? Arch. Biochem. Biophys. 2016;595:120–124. doi: 10.1016/j.abb.2015.11.014. PubMed DOI

Latham L.S., Hensen Z.K., Minor D.S. Chocolate—Guilty pleasure or healthy supplement? J. Clin. Hypertens. 2014;16:101–106. doi: 10.1111/jch.12223. PubMed DOI PMC

Ferri C., Desideri G., Ferri L., Proietti I., Di Agostino S., Martella L., Mai F., Di Giosia P., Grassi D. Cocoa, Blood Pressure, and Cardiovascular Health. J. Agric. Food Chem. 2015;63:9901–9909. doi: 10.1021/acs.jafc.5b01064. PubMed DOI

Ibero-Baraibar I., Suarez M., Arola-Arnal A., Zulet M.A., Martinez J.A. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet. Food Nutr. Res. 2016;60 doi: 10.3402/fnr.v60.30449. PubMed DOI PMC

Hugel H.M., Jackson N., May B., Zhang A.L., Xue C.C. Polyphenol protection and treatment of hypertension. Phytomedicine. 2016;23:220–231. doi: 10.1016/j.phymed.2015.12.012. PubMed DOI

Persson I.A.L., Josefsson M., Persson K., Andersson R.G.G. Tea flavanols inhibit angiotensin-converting enzyme activity and increase nitric oxide production in human endothelial cells. J. Pharm. Pharmacol. 2006;58:1139–1144. doi: 10.1211/jpp.58.8.0016. PubMed DOI

Li X., Dai Y.N., Yan S.J., Shi Y.L., Li J.X., Liu J.L., Cha L., Mu J.J. Resveratrol lowers blood pressure in spontaneously hypertensive rats via calcium-dependent endothelial NO production. Clin. Exp. Hypertens. 2016;38:287–293. doi: 10.3109/10641963.2015.1089882. PubMed DOI

Taguchi K., Hida M., Hasegawa M., Matsumoto T., Kobayashi T. Dietary polyphenol morin rescues endothelial dysfunction in a diabetic mouse model by activating the Akt/eNOS pathway. Mol. Nutr. Food Res. 2016;60:580–588. doi: 10.1002/mnfr.201500618. PubMed DOI

Kim H.S., Quon M.J., Kim J.A. New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biol. 2014;2:187–195. doi: 10.1016/j.redox.2013.12.022. PubMed DOI PMC

Smoliga J.M., Baur J.A., Hausenblas H.A. Resveratrol and health—A comprehensive review of human clinical trials. Mol. Nutr. Food Res. 2011;55:1129–1141. doi: 10.1002/mnfr.201100143. PubMed DOI

Lee D.I., Acosta C., Anderson C.M., Anderson H.D. Peripheral and Cerebral Resistance Arteries in the Spontaneously Hypertensive Heart Failure Rat: Effects of Stilbenoid Polyphenols. Molecules. 2017;22:380. doi: 10.3390/molecules22030380. PubMed DOI PMC

Behbahani J., Thandapilly S.J., Louis X.L., Huang Y.S., Shao Z.J., Kopilas M.A., Wojciechowski P., Netticadan T., Anderson H.D. Resveratrol and Small Artery Compliance and Remodeling in the Spontaneously Hypertensive Rat. Am. J. Hypertens. 2010;23:1273–1278. doi: 10.1038/ajh.2010.161. PubMed DOI

Thandapilly S.J., LeMaistre J.L., Louis X.L., Anderson C.M., Netticadan T., Anderson H.D. Vascular and Cardiac Effects of Grape Powder in the Spontaneously Hypertensive Rat. Am. J. Hypertens. 2012;25:1070–1076. doi: 10.1038/ajh.2012.98. PubMed DOI

Pons Z., Margalef M., Bravo F.I., Arola-Arnal A., Muguerza B. Grape seed flavanols decrease blood pressure via Sirt-1 and confer a vasoprotective pattern in rats. J. Funct. Foods. 2016;24:164–172. doi: 10.1016/j.jff.2016.03.030. DOI

Fleenor B.S., Sindler A.L., Marvi N.K., Howell K.L., Zigler M.L., Yoshizawa M., Seals D.R. Curcumin ameliorates arterial dysfunction and oxidative stress with aging. Exp. Gerontol. 2013;48:269–276. doi: 10.1016/j.exger.2012.10.008. PubMed DOI PMC

Spigoni V., Mena P., Cito M., Fantuzzi F., Bonadonna R.C., Brighenti F., Dei Cas A., Del Rio D. Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells. Molecules. 2016;21:1009. doi: 10.3390/molecules21081009. PubMed DOI PMC

Rowlands D.J., Chapple S., Siow R.C., Mann G.E. Equol-stimulated mitochondrial reactive oxygen species activate endothelial nitric oxide synthase and redox signaling in endothelial cells: Roles for F-actin and GPR30. Hypertension. 2011;57:833–840. doi: 10.1161/HYPERTENSIONAHA.110.162198. PubMed DOI PMC

Cheng C., Wang X., Weakley S.M., Kougias P., Lin P.H., Yao Q., Chen C. The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells. J. Nutr. 2010;140:12–17. doi: 10.3945/jn.109.110981. PubMed DOI PMC

Bonacasa B., Siow R.C., Mann G.E. Impact of dietary soy isoflavones in pregnancy on fetal programming of endothelial function in offspring. Microcirculation. 2011;18:270–285. doi: 10.1111/j.1549-8719.2011.00088.x. PubMed DOI

Egea J., Fabregat I., Frapart Y.M., Ghezzi P., Gorlach A., Kietzmann T., Kubaichuk K., Knaus U.G., Lopez M.G., Olaso-Gonzalez G., et al. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS) Redox Biol. 2017;13:94–162. doi: 10.1016/j.redox.2017.05.007. PubMed DOI PMC

Amiot M.J., Riva C., Vinet A. Effects of dietary polyphenols on metabolic syndrome features in humans: A systematic review. Obes. Rev. 2016;17:573–586. doi: 10.1111/obr.12409. PubMed DOI

Jiang R.J., Hodgson J.M., Mas E., Croft K.D., Ward N.C. Chlorogenic acid improves ex vivo vessel function and protects endothelial cells against HOCl-induced oxidative damage, via increased production of nitric oxide and induction of Hmox-1. J. Nutr. Biochem. 2016;27:53–60. doi: 10.1016/j.jnutbio.2015.08.017. PubMed DOI

Zenkov N.K., Chechushkov A.V., Kozhin P.M., Kandalintseva N.V., Martinovich G.G., Menshchikova E.B. Plant phenols and autophagy. Biochemistry. 2016;81:297–314. doi: 10.1134/S0006297916040015. PubMed DOI

Forman H.J., Davies K.J.A., Ursini F. How Do Nutritional Antioxidants Really Work: Nucleophilic Tone and Para-Hormesis Versus Free Radical Scavenging in vivo. Free Radic. Biol. Med. 2014;74:307. doi: 10.1016/j.freeradbiomed.2014.05.012. PubMed DOI PMC

Mann G.E., Bonacasa B., Ishii T., Siow R.C. Targeting the redox sensitive Nrf2-Keap1 defense pathway in cardiovascular disease: Protection afforded by dietary isoflavones. Curr. Opin. Pharmacol. 2009;9:139–145. doi: 10.1016/j.coph.2008.12.012. PubMed DOI

Zhang T., Liang X., Shi L., Wang L., Chen J., Kang C., Zhu J., Mi M. Estrogen receptor and PI3K/Akt signaling pathway involvement in S-(-)equol-induced activation of Nrf2/ARE in endothelial cells. PLoS ONE. 2013;8:e79075. doi: 10.1371/journal.pone.0079075. PubMed DOI PMC

Chapple S., Rowlands D.J., Siow R., Mann G. The Estrogenic Compound Equol Affords Cardiovascular Protection via Activation of Nrf2 Antioxidant Defenses. Free Radic. Biol. Med. 2012;53:S157. doi: 10.1016/j.freeradbiomed.2012.10.429. DOI

Martin M.A., Ramos S. Cocoa polyphenols in oxidative stress: Potential health implications. J. Funct. Foods. 2016;27:570–588. doi: 10.1016/j.jff.2016.10.008. DOI

Kuntz S., Kunz C., Herrmann J., Borsch C.H., Abel G., Frohling B., Dietrich H., Rudloff S. Anthocyanins from fruit juices improve the antioxidant status of healthy young female volunteers without affecting anti-inflammatory parameters: Results from the randomised, double-blind, placebo-controlled, cross-over ANTHONIA (ANTHOcyanins in Nutrition Investigation Alliance) study. Br. J. Nutr. 2014;112:925–936. doi: 10.1017/s0007114514001482. PubMed DOI

Kivela A.M., Kansanen E., Jyrkkanen H.K., Nurmi T., Yla-Herttuala S., Levonen A.L. Enterolactone induces heme oxygenase-1 expression through nuclear factor-E2-related factor 2 activation in endothelial cells. J. Nutr. 2008;138:1263–1268. doi: 10.1093/jn/138.7.1263. PubMed DOI

Yang H.X., Xiao L., Yuan Y., Luo X.Q., Jiang M.L., Ni J.H., Wang N.P. Procyanidin B2 inhibits NLRP3 inflammasome activation in human vascular endothelial cells. Biochem. Pharmacol. 2014;92:599–606. doi: 10.1016/j.bcp.2014.10.001. PubMed DOI

Misawa T., Saitoh T., Kozaki T., Park S., Takahama M., Akira S. Resveratrol inhibits the acetylated alpha-tubulin-mediated assembly of the NLRP3-inflammasome. Int. Immunol. 2015;27:425–434. doi: 10.1093/intimm/dxv018. PubMed DOI

Shi A.M., Shi H.T., Wang Y., Liu X., Cheng Y., Li H., Zhao H.L., Wang S.N., Dong L. Activation of Nrf2 pathway and inhibition of NLRP3 inflammasome activation contribute to the protective effect of chlorogenic acid on acute liver injury. Int. Immunopharmacol. 2018;54:125–130. doi: 10.1016/j.intimp.2017.11.007. PubMed DOI

El-Bassossy H.M., Hassan N.A., Mahmoud M.F., Fahmy A. Baicalein protects against hypertension associated with diabetes: Effect on vascular reactivity and stiffness. Phytomedicine. 2014;21:1742–1745. doi: 10.1016/j.phymed.2014.08.012. PubMed DOI

Kunnumakkara A.B., Bordoloi D., Padmavathi G., Monisha J., Roy N.K., Prasad S., Aggarwal B.B. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. Br. J. Pharmacol. 2017;174:1325–1348. doi: 10.1111/bph.13621. PubMed DOI PMC

Warner E.F., Zhang Q.Z., Raheem K.S., O’Hagan D., O’Connell M.A., Kay C.D. Common Phenolic Metabolites of Flavonoids, but Not Their Unmetabolized Precursors, Reduce the Secretion of Vascular Cellular Adhesion Molecules by Human Endothelial Cells(1-3) J. Nutr. 2016;146:465–473. doi: 10.3945/jn.115.217943. PubMed DOI PMC

Han Q.A., Yan C., Wang L., Li G., Xu Y., Xia X. Urolithin A attenuates ox-LDL-induced endothelial dysfunction partly by modulating microRNA-27 and ERK/PPAR-gamma pathway. Mol. Nutr. Food Res. 2016;60:1933–1943. doi: 10.1002/mnfr.201500827. PubMed DOI

Fry J.L., Al Sayah L., Weisbrod R.M., Van Roy I., Weng X., Cohen R.A., Bachschmid M.M., Seta F. Vascular Smooth Muscle Sirtuin-1 Protects Against Diet-Induced Aortic Stiffness. Hypertension. 2016;68:775–784. doi: 10.1161/HYPERTENSIONAHA.116.07622. PubMed DOI PMC

Pusparini, Dharma R., Suyatna F.D., Mansyur M., Hidajat A. Effect of soy isoflavone supplementation on vascular endothelial function and oxidative stress in postmenopausal women: A community randomized controlled trial. Asia Pac. J. Clin. Nutr. 2013;22:357–364. doi: 10.6133/apjcn.2013.22.3.13. PubMed DOI

Subedi L., Ji E., Shin D., Jin J., Yeo J.H., Kim S.Y. Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro. Nutrients. 2017;9 doi: 10.3390/nu9030207. PubMed DOI PMC

Xu J., Yuan C., Wang G., Luo J., Ma H., Xu L., Mu Y., Li Y., Seeram N.P., Huang X., et al. Urolithins Attenuate LPS-Induced Neuroinflammation in BV2Microglia via MAPK, Akt, and NF-kappaB Signaling Pathways. J. Agric. Food Chem. 2018;66:571–580. doi: 10.1021/acs.jafc.7b03285. PubMed DOI

Bo S., Ciccone G., Castiglione A., Gambino R., De Michieli F., Villois P., Durazzo M., Cavallo-Perin P., Cassader M. Anti-Inflammatory and Antioxidant Effects of Resveratrol in Healthy Smokers A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial. Curr. Med. Chem. 2013;20:1323–1331. doi: 10.2174/0929867311320100009. PubMed DOI

Rangel-Huerta O.D., Pastor-Villaescusa B., Aguilera C.M., Gil A. A Systematic Review of the Efficacy of Bioactive Compounds in Cardiovascular Disease: Phenolic Compounds. Nutrients. 2015;7:5177–5216. doi: 10.3390/nu7075177. PubMed DOI PMC

Chiva-Blanch G., Urpi-Sarda M., Llorach R., Rotches-Ribalta M., Guillen M., Casas R., Arranz S., Valderas-Martinez P., Portoles O., Corella D. Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: A randomized clinical trial. Am. J. Clin. Nutr. 2012;95:1506. doi: 10.3945/ajcn.111.022889. PubMed DOI

Dong J.Y., Wang P.Y., He K., Qin L.Q. Effect of soy isoflavones on circulating C-reactive protein in postmenopausal women: Meta-analysis of randomized controlled trials. Menopause J. N. Am. Menopause Soc. 2011;18:1256–1262. doi: 10.1097/gme.0b013e31821bfa24. PubMed DOI

Nicastro H.L., Mondul A.M., Rohrmann S., Platz E.A. Associations between urinary soy isoflavonoids and two inflammatory markers in adults in the United States in 2005-2008. Cancer Causes Control. 2013;24:1185–1196. doi: 10.1007/s10552-013-0198-9. PubMed DOI PMC

Ren G.Y., Chen C.Y., Chen G.C., Chen W.G., Pan A., Pan C.W., Zhang Y.H., Qin L.Q., Chen L.H. Effect of Flaxseed Intervention on Inflammatory Marker C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2016;8:12. doi: 10.3390/nu8030136. PubMed DOI PMC

Reger M.K., Zollinger T.W., Liu Z., Jones J., Zhang J. Association between Urinary Phytoestrogens and C-reactive Protein in the Continuous National Health and Nutrition Examination Survey. J. Am. Coll. Nutr. 2017;36:434–441. doi: 10.1080/07315724.2017.1318722. PubMed DOI

Frankenfeld C.L. Cardiometabolic risk factors are associated with high urinary enterolactone concentration, independent of urinary enterodiol concentration and dietary fiber intake in adults. J. Nutr. 2014;144:1445–1453. doi: 10.3945/jn.114.190512. PubMed DOI

Sahebkar A., Gurban C., Serban A., Andrica F., Serban M.C. Effects of supplementation with pomegranate juice on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine. 2016;23:1095–1102. doi: 10.1016/j.phymed.2015.12.008. PubMed DOI

Scoditti E., Capurso C., Capurso A., Massaro M. Vascular effects of the Mediterranean diet-Part II: Role of omega-3 fatty acids and olive oil polyphenols. Vasc. Pharmacol. 2014;63:127–134. doi: 10.1016/j.vph.2014.07.001. PubMed DOI

Konstantinidou V., Covas M.I., Munoz-Aguayo D., Khymenets O., de la Torre R., Saez G., Tormos M.D., Toledo E., Marti A., Ruiz-Gutierrez V., et al. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: A randomized controlled trial. FASEB J. 2010;24:2546–2557. doi: 10.1096/fj.09-148452. PubMed DOI

Calabriso N., Massaro M., Scoditti E., Pellegrino M., Ingrosso I., Giovinazzo G., Carluccio M.A. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and-9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases. Molecules. 2016;21:18. doi: 10.3390/molecules21091147. PubMed DOI PMC

Yahfoufi N., Alsadi N., Jambi M., Matar C. The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients. 2018;10:1618. doi: 10.3390/nu10111618. PubMed DOI PMC

Khangholi S., Majid F.A.A., Berwary N.J.A., Ahmad F., Aziz R.B. The Mechanisms of Inhibition of Advanced Glycation End Products Formation through Polyphenols in Hyperglycemic Condition. Planta Med. 2016;82:32–45. doi: 10.1055/s-0035-1558086. PubMed DOI

Xie Y.X., Chen X.Q. Structures Required of Polyphenols for Inhibiting Advanced Glycation end Products Formation. Curr. Drug Metab. 2013;14:414–431. doi: 10.2174/1389200211314040005. PubMed DOI

Kumagai Y., Nakatani S., Onodera H., Nagatomo A., Nishida N., Matsuura Y., Kobata K., Wada M. Anti-Glycation Effects of Pomegranate (Punica granatum L.) Fruit Extract and Its Components in Vivo and in Vitro. J. Agric. Food Chem. 2015;63:7760–7764. doi: 10.1021/acs.jafc.5b02766. PubMed DOI

Zhuang Y.L., Ma Q.Y., Guo Y., Sun L.P. Purification and identification of rambutan (Nephelium lappaceum) peel phenolics with evaluation of antioxidant and antiglycation activities in vitro. Int. J. Food Sci. Technol. 2017;52:1810–1819. doi: 10.1111/ijfs.13455. DOI

Ma H., Liu W.X., Frost L., Kirschenbaum L.J., Dain J.A., Seeram N.P. Glucitol-core containing gallotannins inhibit the formation of advanced glycation end-products mediated by their antioxidant potential. Food Funct. 2016;7:2213–2222. doi: 10.1039/C6FO00169F. PubMed DOI PMC

Bhuiyan M.N.I., Mitsuhashi S., Sigetomi K., Ubukata M. Quercetin inhibits advanced glycation end product formation via chelating metal ions, trapping methylglyoxal, and trapping reactive oxygen species. Biosci. Biotechnol. Biochem. 2017;81:882–890. doi: 10.1080/09168451.2017.1282805. PubMed DOI

Yeh W.J., Hsia S.M., Lee W.H., Wu C.H. Polyphenols with antiglycation activity and mechanisms of action: A review of recent findings. J. Food Drug Anal. 2017;25:84–92. doi: 10.1016/j.jfda.2016.10.017. PubMed DOI PMC

Navarro M., Morales F.J. Evaluation of an olive leaf extract as a natural source of antiglycative compounds. Food Res. Int. 2017;92:56–63. doi: 10.1016/j.foodres.2016.12.017. PubMed DOI

Navarro M., Morales F.J., Ramos S. Olive leaf extract concentrated in hydroxytyrosol attenuates protein carbonylation and the formation of advanced glycation end products in a hepatic cell line (HepG2) Food Funct. 2017;8:944–953. doi: 10.1039/C6FO01738J. PubMed DOI

Zhang P.W., Tian C., Xu F.Y., Chen Z., Burnside R., Yi W.J., Xiang S.Y., Xie X., Wu N.N., Yang H., et al. Green Tea Polyphenols Alleviate Autophagy Inhibition Induced by High Glucose in Endothelial Cells. Biomed. Environ. Sci. 2016;29:524–528. doi: 10.3967/bes2016.069. PubMed DOI

Holczer M., Besze B., Zambo V., Csala M., Banhegyi G., Kapuy O. Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress. Oxid. Med. Cell. Longev. 2018;2018:6721530. doi: 10.1155/2018/6721530. PubMed DOI PMC

Kim H.S., Montana V., Jang H.J., Parpura V., Kim J.A. Epigallocatechin Gallate (EGCG) Stimulates Autophagy in Vascular Endothelial Cells a potential role for reducing lipid accumulation. J. Biol. Chem. 2013;288:22693–22705. doi: 10.1074/jbc.M113.477505. PubMed DOI PMC

Wang W., Jing T., Yang X., He Y., Wang B., Xiao Y., Shang C., Zhang J., Lin R. Hydroxytyrosol regulates the autophagy of vascular adventitial fibroblasts through the SIRT1-mediated signaling pathway. Can. J. Physiol. Pharmacol. 2018;96:88–96. doi: 10.1139/cjpp-2016-0676. PubMed DOI

Yang X., Jing T., Li Y., He Y., Zhang W., Wang B., Xiao Y., Wang W., Zhang J., Wei J., et al. Hydroxytyrosol Attenuates LPS-Induced Acute Lung Injury in Mice by Regulating Autophagy and Sirtuin Expression. Curr. Mol. Med. 2017;17:149–159. doi: 10.2174/1566524017666170421151940. PubMed DOI

Cetrullo S., D’Adamo S., Guidotti S., Borzi R.M., Flamigni F. Hydroxytyrosol prevents chondrocyte death under oxidative stress by inducing autophagy through sirtuin 1-dependent and -independent mechanisms. Biochim. Biophys. Acta. 2016;1860:1181–1191. doi: 10.1016/j.bbagen.2016.03.002. PubMed DOI

Rigacci S., Miceli C., Nediani C., Berti A., Cascella R., Pantano D., Nardiello P., Luccarini I., Casamenti F., Stefani M. Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: A mechanistic insight. Oncotarget. 2015;6:35344–35357. doi: 10.18632/oncotarget.6119. PubMed DOI PMC

Boakye Y.D., Groyer L., Heiss E.H. An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages. Biochim. Biophys. Acta Gen. Subj. 2018;1862:61–70. doi: 10.1016/j.bbagen.2017.10.006. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...