Review of Evidence and Perspectives of Flavonoids on Metabolic Syndrome and Neurodegenerative Disease

Author(s): Aline M. Hilzendeger Zilli, Eduardo M. Zilli*

Journal Name: Protein & Peptide Letters

Volume 28 , Issue 7 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Flavonoids are commonly found in fruits, vegetables, and plant-derived foods and may promote various health benefits when included in the diet. The biological activity of flavonoids is normally associated to their potent antioxidant and anti-inflammatory effects, since oxidative stress is associated to conditions such as diabetes, obesity, cardiovascular and neurodegenerative diseases. Additionally, flavonoids may be related to metabolic diseases through their effects on inflammatory mediators and pathways, barrier integrity and gut microbiota composition. The extensive metabolism undergone by flavonoids in humans and the individual differences in their bioavailability to target organs hinder the interpretation of results from cell and animal models. Prospective human studies therefore provide an important perspective. In the field of neurodegenerative disease, carefully designed cohort studies have uncovered important associations between flavonoid intake and reduction in dementia risk, especially regarding specific flavonols, but also anthocyanins. Alternative mechanisms of action, such as changes in the gut microbiota or modulation of the production of toxic proteins, such as amyloid and tau, likely account for an important component of their positive effects, and their elucidation may lead to public health benefits of large magnitude.

Keywords: Flavonoids, antioxidant, anti-inflammatory, metabolic syndrome, obesity, gut microbiota, dementia.

Pietta, P.G. Flavonoids as antioxidants. J. Nat. Prod., 2000, 63(7), 1035-1042.
[] [PMID: 10924197]
Wilkin, T.J.; Voss, L.D. Metabolic syndrome: maladaptation to a modern world. J. R. Soc. Med., 2004, 97(11), 511-520.
[] [PMID: 15520144]
Hebert, L.E.; Weuve, J.; Scherr, P.A.; Evans, D.A. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology, 2013, 80(19), 1778-1783.
[] [PMID: 23390181]
Overman, A.; Chuang, C.C.; McIntosh, M. Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media. Int. J. Obes., 2011, 35(9), 1165-1172.
[] [PMID: 21224828]
Sabogal-Guáqueta, A.M.; Muñoz-Manco, J.I.; Ramírez-Pineda, J.R.; Lamprea-Rodriguez, M.; Osorio, E.; Cardona-Gómez, G.P. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology, 2015, 93, 134-145.
[] [PMID: 25666032]
Scholey, A.B.; French, S.J.; Morris, P.J.; Kennedy, D.O.; Milne, A.L.; Haskell, C.F. Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort. J. Psychopharmacol., 2010, 24(10), 1505-1514.
[] [PMID: 19942640]
Whyte, A.R.; Williams, C.M. Effects of a single dose of a flavonoid-rich blueberry drink on memory in 8 to 10 y old children. Nutrition, 2015, 31(3), 531-534.
[] [PMID: 25701345]
Shishtar, E.; Rogers, G.T.; Blumberg, J.B.; Au, R.; Jacques, P.F. Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort. Am. J. Clin. Nutr., 2020, 112(2), 343-353.
[] [PMID: 32320019]
Commenges, D.; Scotet, V.; Renaud, S.; Jacqmin-Gadda, H.; Barberger-Gateau, P.; Dartigues, J.F. Intake of flavonoids and risk of dementia. Eur. J. Epidemiol., 2000, 16(4), 357-363.
[] [PMID: 10959944]
Laurin, D.; Masaki, K.H.; Foley, D.J.; White, L.R.; Launer, L.J. Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. Am. J. Epidemiol., 2004, 159(10), 959-967.
[] [PMID: 15128608]
Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr., 2005, 81(1)(Suppl.), 230S-242S.
[] [PMID: 15640486]
Williamson, G.; Manach, C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am. J. Clin. Nutr., 2005, 81(1)(Suppl.), 243S-255S.
[] [PMID: 15640487]
Hooper, L.; Kroon, P.A.; Rimm, E.B.; Cohn, J.S.; Harvey, I.; Le Cornu, K.A.; Ryder, J.J.; Hall, W.L.; Cassidy, A. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr., 2008, 88(1), 38-50.
[] [PMID: 18614722]
Serafini, M.; Peluso, I.; Raguzzini, A. Flavonoids as anti-inflammatory agents. Proc. Nutr. Soc., 2010, 69(3), 273-278.
[] [PMID: 20569521]
Shishtar, E.; Rogers, G.T.; Blumberg, J.B.; Au, R.; Jacques, P.F. Long-term dietary flavonoid intake and change in cognitive function in the Framingham Offspring cohort. Public Health Nutr., 2020, 23(9), 1576-1588.
[] [PMID: 32090722]
Serafini, M.; Bugianesi, R.; Salucci, M.; Azzini, E.; Raguzzini, A.; Maiani, G. Effect of acute ingestion of fresh and stored lettuce (Lactuca sativa) on plasma total antioxidant capacity and antioxidant levels in human subjects. Br. J. Nutr., 2002, 88(6), 615-623.
[] [PMID: 12493083]
Manach, C.; Donovan, J.L. Pharmacokinetics and metabolism of dietary flavonoids in humans. Free Radic. Res., 2004, 38(8), 771-785.
[] [PMID: 15493450]
Aura, A.M.; Martin-Lopez, P.; O’Leary, K.A.; Williamson, G.; Oksman-Caldentey, K.M.; Poutanen, K.; Santos-Buelga, C. In vitro metabolism of anthocyanins by human gut microflora. Eur. J. Nutr., 2005, 44(3), 133-142.
[] [PMID: 15309431]
Keppler, K.; Humpf, H.U. Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorg. Med. Chem., 2005, 13(17), 5195-5205.
[] [PMID: 15963727]
Meng, X.; Sang, S.; Zhu, N.; Lu, H.; Sheng, S.; Lee, M.J.; Ho, C.T.; Yang, C.S. Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats. Chem. Res. Toxicol., 2002, 15(8), 1042-1050.
[] [PMID: 12184788]
Rios, L.Y.; Gonthier, M.P.; Rémésy, C.; Mila, I.; Lapierre, C.; Lazarus, S.A.; Williamson, G.; Scalbert, A. Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. Am. J. Clin. Nutr., 2003, 77(4), 912-918.
[] [PMID: 12663291]
Vitaglione, P.; Donnarumma, G.; Napolitano, A.; Galvano, F.; Gallo, A.; Scalfi, L.; Fogliano, V. Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J. Nutr., 2007, 137(9), 2043-2048.
[] [PMID: 17709440]
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.
[] [PMID: 20955650]
Cassidy, A.; Minihane, A.M. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am. J. Clin. Nutr., 2017, 105(1), 10-22.
[] [PMID: 27881391]
Del Rio, D.; Borges, G.; Crozier, A. Berry flavonoids and phenolics: bioavailability and evidence of protective effects. Br. J. Nutr., 2010, 104(Suppl. 3), S67-S90.
[] [PMID: 20955651]
van Duynhoven, J.; Vaughan, E.E.; Jacobs, D.M.; Kemperman, R.A.; van Velzen, E.J.; Gross, G.; Roger, L.C.; Possemiers, S.; Smilde, A.K.; Doré, J.; Westerhuis, J.A.; Van de Wiele, T. Metabolic fate of polyphenols in the human superorganism. Proc. Natl. Acad. Sci. USA, 2011, 108(Suppl. 1), 4531-4538.
[] [PMID: 20615997]
Cermak, R.; Breves, G.M. In vitro degradation of the flavonol quercetin and of quercetin glycosides in the porcine hindgut. Arch. Anim. Nutr., 2006, 60(2), 180-189.
[] [PMID: 16649580]
de Ferrars, R.M.; Czank, C.; Zhang, Q.; Botting, N.P.; Kroon, P.A.; Cassidy, A.; Kay, C.D. The pharmacokinetics of anthocyanins and their metabolites in humans. Br. J. Pharmacol., 2014, 171(13), 3268-3282.
[] [PMID: 24602005]
Turnbaugh, P.J.; Hamady, M.; Yatsunenko, T.; Cantarel, B.L.; Duncan, A.; Ley, R.E.; Sogin, M.L.; Jones, W.J.; Roe, B.A.; Affourtit, J.P.; Egholm, M.; Henrissat, B.; Heath, A.C.; Knight, R.; Gordon, J.I. A core gut microbiome in obese and lean twins. Nature, 2009, 457(7228), 480-484.
[] [PMID: 19043404]
Blaut, M.; Clavel, T. Metabolic diversity of the intestinal microbiota: implications for health and disease. J. Nutr., 2007, 137(3)(Suppl. 2), 751S-755S.
[] [PMID: 17311972]
Tomás-Navarro, M.; Vallejo, F.; Sentandreu, E.; Navarro, J.L.; Tomás-Barberán, F.A. Volunteer stratification is more relevant than technological treatment in orange juice flavanone bioavailability. J. Agric. Food Chem., 2014, 62(1), 24-27.
[] [PMID: 24344926]
Simons, A.L.; Renouf, M.; Hendrich, S.; Murphy, P.A. Human gut microbial degradation of flavonoids: structure-function relationships. J. Agric. Food Chem., 2005, 53(10), 4258-4263.
[] [PMID: 15884869]
Roowi, S.; Mullen, W.; Edwards, C.A.; Crozier, A. Yoghurt impacts on the excretion of phenolic acids derived from colonic breakdown of orange juice flavanones in humans. Mol. Nutr. Food Res., 2009, 53(Suppl. 1), S68-S75.
[] [PMID: 19415668]
Czank, C.; Cassidy, A.; Zhang, Q.; Morrison, D.J.; Preston, T.; Kroon, P.A.; Botting, N.P.; Kay, C.D. Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study. Am. J. Clin. Nutr., 2013, 97(5), 995-1003.
[] [PMID: 23604435]
Roopchand, D.E.; Carmody, R.N.; Kuhn, P.; Moskal, K.; Rojas-Silva, P.; Turnbaugh, P.J.; Raskin, I. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes, 2015, 64(8), 2847-2858.
[] [PMID: 25845659]
Anhê, F.F.; Roy, D.; Pilon, G.; Dudonné, S.; Matamoros, S.; Varin, T.V.; Garofalo, C.; Moine, Q.; Desjardins, Y.; Levy, E.; Marette, A. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut, 2015, 64(6), 872-883.
[] [PMID: 25080446]
Galleano, M.; Calabro, V.; Prince, P.D.; Litterio, M.C.; Piotrkowski, B.; Vazquez-Prieto, M.A.; Miatello, R.M.; Oteiza, P.I.; Fraga, C.G. Flavonoids and metabolic syndrome. Ann. N. Y. Acad. Sci., 2012, 1259, 87-94.
[] [PMID: 22758640]
Samson, S.L.; Garber, A.J. Metabolic syndrome. Endocrinol. Metab. Clin. North Am., 2014, 43(1), 1-23.
[] [PMID: 24582089]
Singh, G.M.; Danaei, G.; Farzadfar, F.; Stevens, G.A.; Woodward, M.; Wormser, D.; Kaptoge, S.; Whitlock, G.; Qiao, Q.; Lewington, S.; Di Angelantonio, E.; Vander Hoorn, S.; Lawes, C.M.; Ali, M.K.; Mozaffarian, D.; Ezzati, M. Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group; Asia-Pacific Cohort Studies Collaboration (APCSC); Diabetes Epidemiology: Collaborative analysis of Diagnostic criteria in Europe (DECODE); Emerging Risk Factor Collaboration (ERFC); Prospective Studies Collaboration (PSC). The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS One, 2013, 8(7), e65174.
[] [PMID: 23935815]
Czernichow, S.; Kengne, A.P.; Stamatakis, E.; Hamer, M.; Batty, G.D. Body mass index, waist circumference and waist-hip ratio: which is the better discriminator of cardiovascular disease mortality risk?: evidence from an individual-participant meta-analysis of 82 864 participants from nine cohort studies. Obes. Rev., 2011, 12(9), 680-687.
[] [PMID: 21521449]
Lauby-Secretan, B.; Scoccianti, C.; Loomis, D.; Grosse, Y.; Bianchini, F.; Straif, K. International Agency for Research on Cancer Handbook Working Group. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N. Engl. J. Med., 2016, 375(8), 794-798.
[] [PMID: 27557308]
Anstey, K.J.; Cherbuin, N.; Budge, M.; Young, J. Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes. Rev., 2011, 12(5), e426-e437.
[] [PMID: 21348917]
Scalbert, A; Williamson, G Dietary intake and bioavailability of polyphenols. J Nutr., 2000, 130(8S), 2073S-85S.
USDA. Dietary Guidelines for Americans; US Department of Agriculture and Department of Health and Human Services. 6th ed. Washington, DC, 2005.
Estaquio, C.; Castetbon, K.; Kesse-Guyot, E.; Bertrais, S.; Deschamps, V.; Dauchet, L.; Péneau, S.; Galan, P.; Hercberg, S. The French National Nutrition and Health Program score is associated with nutritional status and risk of major chronic diseases. J. Nutr., 2008, 138(5), 946-953.
[] [PMID: 18424606]
Patel, R.V.; Mistry, B.M.; Shinde, S.K.; Syed, R.; Singh, V.; Shin, H.S. Therapeutic potential of quercetin as a cardiovascular agent. Eur. J. Med. Chem., 2018, 155, 889-904.
[] [PMID: 29966915]
Larson, A.J.; Symons, J.D.; Jalili, T. Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv. Nutr., 2012, 3(1), 39-46.
[] [PMID: 22332099]
Serban, M.C.; Sahebkar, A.; Zanchetti, A.; Mikhailidis, D.P.; Howard, G.; Antal, D.; Andrica, F.; Ahmed, A.; Aronow, W.S.; Muntner, P.; Lip, G.Y.; Graham, I.; Wong, N.; Rysz, J.; Banach, M. Lipid and Blood Pressure Meta‐analysis Collaboration (LBPMC) Group. Effects of quercetin on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J. Am. Heart Assoc., 2016, 5(7), e002713.
[] [PMID: 27405810]
Dhanya, R.; Arya, A.D.; Nisha, P.; Jayamurthy, P. Quercetin, a lead compound against type 2 diabetes ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line. Front. Pharmacol., 2017, 8, 336.
[] [PMID: 28642704]
Joshi, T.; Singh, A.K.; Haratipour, P.; Sah, A.N.; Pandey, A.K.; Naseri, R.; Juyal, V.; Farzaei, M.H. Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications. J. Cell. Physiol., 2019, 234(10), 17212-17231.
[] [PMID: 30916407]
Eid, H.M.; Haddad, P.S. The antidiabetic potential of quercetin: underlying mechanisms. Curr. Med. Chem., 2017, 24(4), 355-364.
[] [PMID: 27633685]
Simioni, C.; Zauli, G.; Martelli, A.M.; Vitale, M.; Sacchetti, G.; Gonelli, A.; Neri, L.M. Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging. Oncotarget, 2018, 9(24), 17181-17198.
[] [PMID: 29682215]
Ola, M.S.; Ahmed, M.M.; Shams, S.; Al-Rejaie, S.S. Neuroprotective effects of quercetin in diabetic rat retina. Saudi J. Biol. Sci., 2017, 24(6), 1186-1194.
[] [PMID: 28855811]
Shi, G.J.; Li, Y.; Cao, Q.H.; Wu, H.X.; Tang, X.Y.; Gao, X.H.; Yu, J.Q.; Chen, Z.; Yang, Y. In vitro and in vivo evidence that quercetin protects against diabetes and its complications: a systematic review of the literature. Biomed. Pharmacother., 2019, 109, 1085-1099.
[] [PMID: 30551359]
Visioli, F.; De La Lastra, C.A.; Andres-Lacueva, C.; Aviram, M.; Calhau, C.; Cassano, A.; D’Archivio, M.; Faria, A.; Favé, G.; Fogliano, V.; Llorach, R.; Vitaglione, P.; Zoratti, M.; Edeas, M. Polyphenols and human health: a prospectus. Crit. Rev. Food Sci. Nutr., 2011, 51(6), 524-546.
[] [PMID: 21929330]
Marventano, S.; Kolacz, P.; Castellano, S.; Galvano, F.; Buscemi, S.; Mistretta, A.; Grosso, G. A review of recent evidence in human studies of n-3 and n-6 PUFA intake on cardiovascular disease, cancer, and depressive disorders: does the ratio really matter? Int. J. Food Sci. Nutr., 2015, 66(6), 611-622.
[] [PMID: 26307560]
Barth, S.W.; Koch, T.C.; Watzl, B.; Dietrich, H.; Will, F.; Bub, A. Moderate effects of apple juice consumption on obesity-related markers in obese men: impact of diet-gene interaction on body fat content. Eur. J. Nutr., 2012, 51(7), 841-850.
[] [PMID: 22038464]
Dallas, C.; Gerbi, A.; Elbez, Y.; Caillard, P.; Zamaria, N.; Cloarec, M. Clinical study to assess the efficacy and safety of a citrus polyphenolic extract of red orange, grapefruit, and orange (Sinetrol-XPur) on weight management and metabolic parameters in healthy overweight individuals. Phytother. Res., 2014, 28(2), 212-218.
[] [PMID: 23554029]
Most, J.; Goossens, G.H.; Jocken, J.W.; Blaak, E.E. Short-term supplementation with a specific combination of dietary polyphenols increases energy expenditure and alters substrate metabolism in overweight subjects. Int. J. Obes., 2014, 38(5), 698-706.
[] [PMID: 24317366]
Bell, Z.W.; Canale, R.E.; Bloomer, R.J. A dual investigation of the effect of dietary supplementation with licorice flavonoid oil on anthropometric and biochemical markers of health and adiposity. Lipids Health Dis., 2011, 10, 29.
[] [PMID: 21310080]
Janssens, P.L.; Hursel, R.; Westerterp-Plantenga, M.S. Long-term green tea extract supplementation does not affect fat absorption, resting energy expenditure, and body composition in adults. J. Nutr., 2015, 145(5), 864-870.
[] [PMID: 25740906]
Rangel-Huerta, O.D.; Aguilera, C.M.; Martin, M.V.; Soto, M.J.; Rico, M.C.; Vallejo, F.; Tomas-Barberan, F.; Perez-de-la-Cruz, A.J.; Gil, A.; Mesa, M.D. Normal or high polyphenol concentration in orange juice affects antioxidant activity, blood pressure, and body weight in obese or overweight adults. J. Nutr., 2015, 145(8), 1808-1816.
[] [PMID: 26136593]
Marranzano, M.; Ray, S.; Godos, J.; Galvano, F. Association between dietary flavonoids intake and obesity in a cohort of adults living in the Mediterranean area. Int. J. Food Sci. Nutr., 2018, 69(8), 1020-1029.
[] [PMID: 29575952]
Ng, M.; Fleming, T.; Robinson, M.; Thomson, B.; Graetz, N.; Margono, C.; Mullany, E.C.; Biryukov, S.; Abbafati, C.; Abera, S.F.; Abraham, J.P.; Abu-Rmeileh, N.M.; Achoki, T.; AlBuhairan, F.S.; Alemu, Z.A.; Alfonso, R.; Ali, M.K.; Ali, R.; Guzman, N.A.; Ammar, W.; Anwari, P.; Banerjee, A.; Barquera, S.; Basu, S.; Bennett, D.A.; Bhutta, Z.; Blore, J.; Cabral, N.; Nonato, I.C.; Chang, J.C.; Chowdhury, R.; Courville, K.J.; Criqui, M.H.; Cundiff, D.K.; Dabhadkar, K.C.; Dandona, L.; Davis, A.; Dayama, A.; Dharmaratne, S.D.; Ding, E.L.; Durrani, A.M.; Esteghamati, A.; Farzadfar, F.; Fay, D.F.; Feigin, V.L.; Flaxman, A.; Forouzanfar, M.H.; Goto, A.; Green, M.A.; Gupta, R.; Hafezi-Nejad, N.; Hankey, G.J.; Harewood, H.C.; Havmoeller, R.; Hay, S.; Hernandez, L.; Husseini, A.; Idrisov, B.T.; Ikeda, N.; Islami, F.; Jahangir, E.; Jassal, S.K.; Jee, S.H.; Jeffreys, M.; Jonas, J.B.; Kabagambe, E.K.; Khalifa, S.E.; Kengne, A.P.; Khader, Y.S.; Khang, Y.H.; Kim, D.; Kimokoti, R.W.; Kinge, J.M.; Kokubo, Y.; Kosen, S.; Kwan, G.; Lai, T.; Leinsalu, M.; Li, Y.; Liang, X.; Liu, S.; Logroscino, G.; Lotufo, P.A.; Lu, Y.; Ma, J.; Mainoo, N.K.; Mensah, G.A.; Merriman, T.R.; Mokdad, A.H.; Moschandreas, J.; Naghavi, M.; Naheed, A.; Nand, D.; Narayan, K.M.; Nelson, E.L.; Neuhouser, M.L.; Nisar, M.I.; Ohkubo, T.; Oti, S.O.; Pedroza, A.; Prabhakaran, D.; Roy, N.; Sampson, U.; Seo, H.; Sepanlou, S.G.; Shibuya, K.; Shiri, R.; Shiue, I.; Singh, G.M.; Singh, J.A.; Skirbekk, V.; Stapelberg, N.J.; Sturua, L.; Sykes, B.L.; Tobias, M.; Tran, B.X.; Trasande, L.; Toyoshima, H.; van de Vijver, S.; Vasankari, T.J.; Veerman, J.L.; Velasquez-Melendez, G.; Vlassov, V.V.; Vollset, S.E.; Vos, T.; Wang, C.; Wang, X.; Weiderpass, E.; Werdecker, A.; Wright, J.L.; Yang, Y.C.; Yatsuya, H.; Yoon, J.; Yoon, S.J.; Zhao, Y.; Zhou, M.; Zhu, S.; Lopez, A.D.; Murray, C.J.; Gakidou, E. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2014, 384(9945), 766-781.
[] [PMID: 24880830]
Chooi, Y.C.; Ding, C.; Magkos, F. The epidemiology of obesity. Metabolism, 2019, 92, 6-10.
[] [PMID: 30253139]
GBoDS. Global burden of disease study 2015 (GBD 2015) obesity and overweight prevalence 1980-2015, 2017.
Fernández-Sánchez, A.; Madrigal-Santillán, E.; Bautista, M.; Esquivel-Soto, J.; Morales-González, A.; Esquivel-Chirino, C.; Durante-Montiel, I.; Sánchez-Rivera, G.; Valadez-Vega, C.; Morales-González, J.A. Inflammation, oxidative stress, and obesity. Int. J. Mol. Sci., 2011, 12(5), 3117-3132.
[] [PMID: 21686173]
Imessaoudene, A.; Merzouk, H.; Berroukeche, F.; Mokhtari, N.; Bensenane, B.; Cherrak, S.; Merzouk, S.A.; Elhabiri, M. Beneficial effects of quercetin-iron complexes on serum and tissue lipids and redox status in obese rats. J. Nutr. Biochem., 2016, 29, 107-115.
[] [PMID: 26895671]
Grobe, J.L.; Rahmouni, K. The adipose/circulating renin-angiotensin system cross-talk enters a new dimension. Hypertension, 2012, 60(6), 1389-1390.
[] [PMID: 23108659]
Guzik, T.J.; Mangalat, D.; Korbut, R. Adipocytokines - novel link between inflammation and vascular function? J. Physiol. Pharmacol., 2006, 57(4), 505-528.
[PMID: 17229978]
Hotamisligil, G.S.; Shargill, N.S.; Spiegelman, B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 1993, 259(5091), 87-91.
[] [PMID: 7678183]
Bleau, C.; Karelis, A.D.; St-Pierre, D.H.; Lamontagne, L. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes. Diabetes Metab. Res. Rev., 2015, 31(6), 545-561.
[] [PMID: 25352002]
Fraga, C.G.; Oteiza, P.I. Dietary flavonoids: role of (-)-epicatechin and related procyanidins in cell signaling. Free Radic. Biol. Med., 2011, 51(4), 813-823.
[] [PMID: 21699974]
Vazquez-Prieto, M.A.; Renna, N.F.; Diez, E.R.; Cacciamani, V.; Lembo, C.; Miatello, R.M. Effect of red wine on adipocytokine expression and vascular alterations in fructose-fed rats. Am. J. Hypertens., 2011, 24(2), 234-240.
[] [PMID: 20885371]
Rivera, L.; Morón, R.; Sánchez, M.; Zarzuelo, A.; Galisteo, M. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring), 2008, 16(9), 2081-2087.
[] [PMID: 18551111]
Terra, X.; Montagut, G.; Bustos, M.; Llopiz, N.; Ardèvol, A.; Bladé, C.; Fernández-Larrea, J.; Pujadas, G.; Salvadó, J.; Arola, L.; Blay, M. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J. Nutr. Biochem., 2009, 20(3), 210-218.
[] [PMID: 18602813]
Terra, X.; Pallarés, V.; Ardèvol, A.; Bladé, C.; Fernández-Larrea, J.; Pujadas, G.; Salvadó, J.; Arola, L.; Blay, M. Modulatory effect of grape-seed procyanidins on local and systemic inflammation in diet-induced obesity rats. J. Nutr. Biochem., 2011, 22(4), 380-387.
[] [PMID: 20655715]
Azuma, T.; Shigeshiro, M.; Kodama, M.; Tanabe, S.; Suzuki, T. Supplemental naringenin prevents intestinal barrier defects and inflammation in colitic mice. J. Nutr., 2013, 143(6), 827-834.
[] [PMID: 23596159]
Amasheh, M.; Luettig, J.; Amasheh, S.; Zeitz, M.; Fromm, M.; Schulzke, J.D. Effects of quercetin studied in colonic HT-29/B6 cells and rat intestine in vitro . Ann. N. Y. Acad. Sci., 2012, 1258, 100-107.
[] [PMID: 22731722]
Etxeberria, U.; Arias, N.; Boqué, N.; Macarulla, M.T.; Portillo, M.P.; Martínez, J.A.; Milagro, F.I. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J. Nutr. Biochem., 2015, 26(6), 651-660.
[] [PMID: 25762527]
Massot-Cladera, M.; Abril-Gil, M.; Torres, S.; Franch, A.; Castell, M.; Pérez-Cano, F.J. Impact of cocoa polyphenol extracts on the immune system and microbiota in two strains of young rats. Br. J. Nutr., 2014, 112(12), 1944-1954.
[] [PMID: 25345541]
Lee, H.C.; Jenner, A.M.; Low, C.S.; Lee, Y.K. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Res. Microbiol., 2006, 157(9), 876-884.
[] [PMID: 16962743]
Parkar, S.G.; Stevenson, D.E.; Skinner, M.A. The potential influence of fruit polyphenols on colonic microflora and human gut health. Int. J. Food Microbiol., 2008, 124(3), 295-298.
[] [PMID: 18456359]
Gil-Cardoso, K.; Ginés, I.; Pinent, M.; Ardévol, 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(2), 234-248.
[] [PMID: 27841104]
Patterson, E.; Ryan, P.M.; Cryan, J.F.; Dinan, T.G.; Ross, R.P.; Fitzgerald, G.F.; Stanton, C. Gut microbiota, obesity and diabetes. Postgrad. Med. J., 2016, 92(1087), 286-300.
[] [PMID: 26912499]
Tzounis, X.; Rodriguez-Mateos, A.; Vulevic, J.; Gibson, G.R.; Kwik-Uribe, C.; Spencer, J.P. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am. J. Clin. Nutr., 2011, 93(1), 62-72.
[] [PMID: 21068351]
Marques, C.; Fernandes, I.; Meireles, M.; Faria, A.; Spencer, J.P.E.; Mateus, N.; Calhau, C. Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins. Sci. Rep., 2018, 8(1), 11341.
[] [PMID: 30054537]
Petersson, S.D.; Philippou, E. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence. Adv. Nutr., 2016, 7(5), 889-904.
[] [PMID: 27633105]
Devore, E.E.; Grodstein, F.; van Rooij, F.J.; Hofman, A.; Stampfer, M.J.; Witteman, J.C.; Breteler, M.M. Dietary antioxidants and long-term risk of dementia. Arch. Neurol., 2010, 67(7), 819-825.
[] [PMID: 20625087]
Holland, T.M.; Agarwal, P.; Wang, Y.; Leurgans, S.E.; Bennett, D.A.; Booth, S.L.; Morris, M.C. Dietary flavonols and risk of Alzheimer dementia. Neurology, 2020, 94(16), e1749-e1756.
[] [PMID: 31996451]
Orhan, I.E.; Daglia, M.; Nabavi, S.F.; Loizzo, M.R.; Sobarzo-Sánchez, E.; Nabavi, S.M. Flavonoids and dementia: an update. Curr. Med. Chem., 2015, 22(8), 1004-1015.
[] [PMID: 25515512]
Root, M.; Ravine, E.; Harper, A. Flavonol intake and cognitive decline in middle-aged adults. J. Med. Food, 2015, 18(12), 1327-1332.
[] [PMID: 26325006]
Procházková, D.; Boušová, I.; Wilhelmová, N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia, 2011, 82(4), 513-523.
[] [PMID: 21277359]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 27 January, 2021
Page: [725 - 734]
Pages: 10
DOI: 10.2174/0929866528666210127152359
Price: $65

Article Metrics

PDF: 103