945
Views
62
CrossRef citations to date
0
Altmetric
Review

Modulation of Chronic Inflammation by Quercetin: The Beneficial Effects on Obesity

& ORCID Icon
Pages 421-431 | Published online: 04 Aug 2020

References

  • Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114(2):147–152. doi:10.1172/JCI2242215254578
  • Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 2008;57(12):3239–3246. doi:10.2337/db08-087218829989
  • Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18(3):363–374. doi:10.1038/nm.262722395709
  • Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med. 1999;340(2):115–126. doi:10.1056/NEJM1999011434002079887164
  • Zielinska D, Wiczkowski W, Piskula MK. Determination of the relative contribution of quercetin and its glucosides to the antioxidant capacity of onion by cyclic voltammetry and spectrophotometric methods. J Agric Food Chem. 2008;56(10):3524–3531. doi:10.1021/jf073521f18454541
  • Ioku K, Aoyama Y, Tokuno A, et al. Various cooking methods and the flavonoid content in onion. J Nutr Sci Vitaminol. 2001;47(1):78–83. doi:10.3177/jnsv.47.7811349895
  • Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167. doi:10.3390/nu803016726999194
  • Marcolin E, San-Miguel B, Vallejo D, et al. Quercetin treatment ameliorates inflammation and fibrosis in mice with nonalcoholic steatohepatitis. J Nutr. 2012;142(10):1821–1828. doi:10.3945/jn.112.16527422915297
  • Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008;585(2–3):325–337. doi:10.1016/j.ejphar.2008.03.00818417116
  • Yen GC, Duh PD, Tsai HL, Huang SL. Pro-oxidative properties of flavonoids in human lymphocytes. Biosci Biotechnol Biochem. 2003;67(6):1215–1222. doi:10.1271/bbb.67.121512843645
  • Dajas F, Abin-Carriquiry JA, Arredondo F, et al. Quercetin in brain diseases: potential and limits. Neurochem Int. 2015;89:140–148. doi:10.1016/j.neuint.2015.07.00226160469
  • Kedhari Sundaram M, Hussain A, Haque S, et al. Quercetin modifies 5ʹCpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells. J Cell Biochem. 2019;120(10):18357–18369. doi:10.1002/jcb.2914731172592
  • Sato S, Norikura T, Mukai Y. Maternal quercetin intake during lactation attenuates renal inflammation and modulates autophagy flux in high-fructose-diet-fed female rat offspring exposed to maternal malnutrition. Food Funct. 2019;10(8):5018–5031. doi:10.1039/c9fo01134j31355385
  • Khiari Z, Makris DP. Stability and transformation of major flavonols in onion (Allium cepa) solid wastes. J Food Sci Technol. 2012;49(4):489–494. doi:10.1007/s13197-010-0201-323904658
  • Hollman PC, van Trijp JM, Buysman MN, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett. 1997;418(1–2):152–156. doi:10.1016/s0014-5793(97)01367-79414116
  • Nishimuro H, Ohnishi H, Sato M, et al. Estimated daily intake and seasonal food sources of quercetin in Japan. Nutrients. 2015;7(4):2345–2358. doi:10.3390/nu704234525849945
  • Lu X, Ross CF, Powers JR, Rasco BA. Determination of quercetins in onion (Allium cepa) using infrared spectroscopy. J Agric Food Chem. 2011;59(12):6376–6382. doi:10.1021/jf200953z21612277
  • Miean KH, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem. 2001;49(6):3106–3112. doi:10.1021/jf000892m11410016
  • Andarwulan N, Batari R, Sandrasari DA, et al. Flavonoid content and antioxidant activity of vegetables from Indonesia. Food Chem. 2010;121(4):1231–1235. doi:10.1016/j.foodchem.2010.01.03328814820
  • Yang RY, Lin S, Kuo G. Content and distribution of flavonoids among 91 edible plant species. Asia Pac J Clin Nutr. 2008;17(Suppl 1):275–279.18296355
  • Hollman PC, de Vries JH, van Leeuwen SD, et al. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr. 1995;62(6):1276–1282. doi:10.1093/ajcn/62.6.12767491892
  • Lotito SB, Zhang WJ, Yang CS, et al. Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radic Biol Med. 2011;51(2):454–463. doi:10.1016/j.freeradbiomed.2011.04.03221571063
  • Cialdella-Kam L, Nieman DC, Sha W, et al. Dose-response to 3 months of quercetin-containing supplements on metabolite and quercetin conjugate profile in adults. Br J Nutr. 2013;109(11):1923–1933. doi:10.1017/S000711451200397223151341
  • de Luca C, Olefsky JM. Inflammation and insulin resistance. FEBS Lett. 2008;582(1):97–105. doi:10.1016/j.febslet.2007.11.05718053812
  • Russell RR 3rd, Bergeron R, Shulman GI, Young LH. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am J Physiol. 1999;277(2):H643–H649. doi:10.1152/ajpheart.1999.277.2.H64310444490
  • Mackenzie RW, Elliott BT. Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes. Diabetes Metab Syndr Obes. 2014;7:55–64. doi:10.2147/DMSO.S4826024611020
  • Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010;314(1):1–16. doi:10.1016/j.mce.2009.07.03119682539
  • Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132(6):2169–2180. doi:10.1053/j.gastro.2007.03.05917498510
  • Boden G. Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes. 2011;18(2):139–143. doi:10.1097/MED.0b013e3283444b0921297467
  • Glass CK, Olefsky JM. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab. 2012;15(5):635–645. doi:10.1016/j.cmet.2012.04.00122560216
  • Spagnuolo C, Moccia S, Russo GL. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem. 2018;153:105–115. doi:10.1016/j.ejmech.2017.09.00128923363
  • Akash MSH, Rehman K, Liaqat A. Tumor necrosis factor-alpha: role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2018;119(1):105–110. doi:10.1002/jcb.2617428569437
  • Overman A, Chuang CC, McIntosh M. Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media. Int J Obes. 2011;35(9):1165–1172. doi:10.1038/ijo.2010.272
  • Forney LA, Lenard NR, Stewart LK, Henagan TM. Dietary quercetin attenuates adipose tissue expansion and inflammation and alters adipocyte morphology in a tissue-specific manner. Int J Mol Sci. 2018;19(3):895. doi:10.3390/ijms19030895
  • Yang J, Kim CS, Tu TH, et al. Quercetin protects obesity-induced hypothalamic inflammation by reducing microglia-mediated inflammatory responses via HO-1 induction. Nutrients. 2017;9(7):650. doi:10.3390/nu9070650
  • Vazquez Prieto MA, Bettaieb A, Rodriguez Lanzi C, et al. Catechin and quercetin attenuate adipose inflammation in fructose-fed rats and 3T3-L1 adipocytes. Mol Nutr Food Res. 2015;59(4):622–633. doi:10.1002/mnfr.20140063125620282
  • Zhang ZJ, Cheang LC, Wang MW, Lee SM. Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish. Int J Mol Med. 2011;27(2):195–203. doi:10.3892/ijmm.2010.57121132259
  • Lee SG, Kim M, Kim CE, et al. Quercetin 3,7-O-dimethyl ether from Siegesbeckia pubescens suppress the production of inflammatory mediators in lipopolysaccharide-induced macrophages and colon epithelial cells. Biosci Biotechnol Biochem. 2016;80(11):2080–2086. doi:10.1080/09168451.2016.120421927405734
  • Carlsen I, Frokiaer J, Norregaard R. Quercetin attenuates cyclooxygenase-2 expression in response to acute ureteral obstruction. Am J Physiol Renal Physiol. 2015;308(11):F1297–F1305. doi:10.1152/ajprenal.00514.201425810437
  • Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34(5):637–650. doi:10.1016/j.immuni.2011.05.00621616434
  • Jia L, Vianna CR, Fukuda M, et al. Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance. Nat Commun. 2014;5:3878. doi:10.1038/ncomms487824815961
  • Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461. doi:10.3389/fimmu.2014.0046125309543
  • Suganami T, Tanimoto-Koyama K, Nishida J, et al. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol. 2007;27(1):84–91. doi:10.1161/01.ATV.0000251608.09329.9a17082484
  • Ghosh AK, O’Brien M, Mau T, Yung R. Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging. Aging (Albany NY). 2017;9(9):1971–1982. doi:10.18632/aging.10128828898202
  • Wu M, Liu F, Guo Q. Quercetin attenuates hypoxia-ischemia induced brain injury in neonatal rats by inhibiting TLR4/NF-kappaB signaling pathway. Int Immunopharmacol. 2019;74:105704. doi:10.1016/j.intimp.2019.10570431228815
  • Li T, Li F, Liu X, et al. Synergistic anti-inflammatory effects of quercetin and catechin via inhibiting activation of TLR4-MyD88-mediated NF-kappaB and MAPK signaling pathways. Phytother Res. 2019;33(3):756–767. doi:10.1002/ptr.626830637814
  • Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-kappaB signaling and inflammation: impact on healthspan and lifespan. J Mol Med. 2011;89(7):667–676. doi:10.1007/s00109-011-0748-021431325
  • Jing Y, Wu F, Li D, et al. Metformin improves obesity-associated inflammation by altering macrophages polarization. Mol Cell Endocrinol. 2018;461:256–264. doi:10.1016/j.mce.2017.09.02528935544
  • Sharma K. Obesity, oxidative stress, and fibrosis in chronic kidney disease. Kidney Int Suppl. 2014;4(1):113–117. doi:10.1038/kisup.2014.21
  • Dugan LL, You YH, Ali SS, et al. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest. 2013;123(11):4888–4899. doi:10.1172/JCI6621824135141
  • Wang S, Moustaid-Moussa N, Chen L, et al. Novel insights of dietary polyphenols and obesity. J Nutr Biochem. 2014;25(1):1–18. doi:10.1016/j.jnutbio.2013.09.00124314860
  • Ahn J, Lee H, Kim S, et al. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun. 2008;373(4):545–549. doi:10.1016/j.bbrc.2008.06.07718586010
  • Choi H, Kim CS, Yu R. Quercetin upregulates uncoupling protein 1 in white/brown adipose tissues through sympathetic stimulation. J Obes Metab Syndr. 2018;27(2):102–109. doi:10.7570/jomes.2018.27.2.10231089549
  • Liu K, Mei F, Wang Y, et al. Quercetin oppositely regulates insulin-mediated glucose disposal in skeletal muscle under normal and inflammatory conditions: the dual roles of AMPK activation. Mol Nutr Food Res. 2016;60(3):551–565. doi:10.1002/mnfr.20150050926627467
  • Dong J, Zhang X, Zhang L, et al. Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKalpha1/SIRT1. J Lipid Res. 2014;55(3):363–374. doi:10.1194/jlr.M03878624465016
  • Hung CH, Chan SH, Chu PM, Tsai KL. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol Nutr Food Res. 2015;59(10):1905–1917. doi:10.1002/mnfr.20150014426202455
  • Qiu L, Luo Y, Chen X. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats. Biomed Pharmacother. 2018;103:1585–1591. doi:10.1016/j.biopha.2018.05.00329864946
  • Chen BL, Wang LT, Huang KH, et al. Quercetin attenuates renal ischemia/reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway. J Nutr Biochem. 2014;25(11):1226–1234. doi:10.1016/j.jnutbio.2014.05.01325087994
  • Cao H, Jia Q, Shen D, et al. Quercetin has a protective effect on atherosclerosis via enhancement of autophagy in ApoE(-/-) mice. Exp Ther Med. 2019;18(4):2451–2458. doi:10.3892/etm.2019.785131555357
  • Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389(6651):610–614. doi:10.1038/393359335502
  • Furuya DT, Poletto AC, Favaro RR, et al. Anti-inflammatory effect of atorvastatin ameliorates insulin resistance in monosodium glutamate-treated obese mice. Metabolism. 2010;59(3):395–399. doi:10.1016/j.metabol.2009.08.01119800637
  • Thrush AB, Heigenhauser GJ, Mullen KL, et al. Palmitate acutely induces insulin resistance in isolated muscle from obese but not lean humans. Am J Physiol Regul Integr Comp Physiol. 2008;294(4):R1205–R1212. doi:10.1152/ajpregu.00909.200718305020
  • Thrush AB, Antoun G, Nikpay M, et al. Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism. Int J Obes. 2018;42(3):353–362. doi:10.1038/ijo.2017.286
  • Anhe GF, Okamoto MM, Kinote A, et al. Quercetin decreases inflammatory response and increases insulin action in skeletal muscle of ob/ob mice and in L6 myotubes. Eur J Pharmacol. 2012;689(1–3):285–293. doi:10.1016/j.ejphar.2012.06.00722713545
  • Kim Y, Kim CS, Joe Y, Chung HT, Ha TY, Yu R. Quercetin reduces tumor necrosis factor alpha-induced muscle atrophy by upregulation of heme oxygenase-1. J Med Food. 2018;21(6):551–559. doi:10.1089/jmf.2017.410829569982
  • Le NH, Kim CS, Park T, et al. Quercetin protects against obesity-induced skeletal muscle inflammation and atrophy. Mediators Inflamm. 2014;2014:834294. doi:10.1155/2014/83429425614714
  • Taleb S. Inflammation in atherosclerosis. Arch Cardiovasc Dis. 2016;109(12):708–715. doi:10.1016/j.acvd.2016.04.00227595467
  • Cao H, Jia Q, Yan L, Chen C, Xing S, Shen D. Quercetin suppresses the progression of atherosclerosis by regulating MST1-mediated autophagy in ox-LDL-induced RAW264.7 macrophage foam cells. Int J Mol Sci. 2019;20(23):6093. doi:10.3390/ijms20236093
  • Wang T, Zhang L, Hu J, et al. Mst1 participates in the atherosclerosis progression through macrophage autophagy inhibition and macrophage apoptosis enhancement. J Mol Cell Cardiol. 2016;98:108–116. doi:10.1016/j.yjmcc.2016.08.00227496379
  • Cai X, Bao L, Ding Y, et al. Quercetin alleviates cell apoptosis and inflammation via the ER stress pathway in vascular endothelial cells cultured in high concentrations of glucosamine. Mol Med Rep. 2017;15(2):825–832. doi:10.3892/mmr.2016.605428000870
  • Si TL, Liu Q, Ren YF, et al. Enhanced anti-inflammatory effects of DHA and quercetin in lipopolysaccharide-induced RAW264.7 macrophages by inhibiting NF-kappaB and MAPK activation. Mol Med Rep. 2016;14(1):499–508. doi:10.3892/mmr.2016.525927176922
  • Bhaskar S, Helen A. Quercetin modulates toll-like receptor-mediated protein kinase signaling pathways in oxLDL-challenged human PBMCs and regulates TLR-activated atherosclerotic inflammation in hypercholesterolemic rats. Mol Cell Biochem. 2016;423(1–2):53–65. doi:10.1007/s11010-016-2824-927665434
  • Lin W, Wang W, Wang D, Ling W. Quercetin protects against atherosclerosis by inhibiting dendritic cell activation. Mol Nutr Food Res. 2017;61(9):1700031. doi:10.1002/mnfr.201700031
  • Brull V, Burak C, Stoffel-Wagner B, et al. No effects of quercetin from onion skin extract on serum leptin and adiponectin concentrations in overweight-to-obese patients with (pre-)hypertension: a randomized double-blinded, placebo-controlled crossover trial. Eur J Nutr. 2017;56(7):2265–2275. doi:10.1007/s00394-016-1267-027423432
  • Dower JI, Geleijnse JM, Gijsbers L, et al. Supplementation of the pure flavonoids epicatechin and quercetin affects some biomarkers of endothelial dysfunction and inflammation in (pre)hypertensive adults: a randomized double-blind, placebo-controlled, crossover trial. J Nutr. 2015;145(7):1459–1463. doi:10.3945/jn.115.21188825972527
  • Lee KH, Park E, Lee HJ, et al. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutr Res Pract. 2011;5(1):28–33. doi:10.4162/nrp.2011.5.1.2821487493
  • Zahedi M, Ghiasvand R, Feizi A, et al. Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes: a double-blind randomized controlled clinical trial. Int J Prev Med. 2013;4(7):777–785.24049596
  • Rezvan N, Moini A, Janani L, et al. Effects of quercetin on adiponectin-mediated insulin sensitivity in polycystic ovary syndrome: a randomized placebo-controlled double-blind clinical trial. Horm Metab Res. 2017;49(2):115–121. doi:10.1055/s-0042-11870527824398
  • Javadi F, Eghtesadi S, Ahmadzadeh A, et al. The effect of quercetin on plasma oxidative status, C-reactive protein and blood pressure in women with rheumatoid arthritis. Int J Prev Med. 2014;5(3):293–301.24829713
  • Javadi F, Ahmadzadeh A, Eghtesadi S, et al. The effect of quercetin on inflammatory factors and clinical symptoms in women with rheumatoid arthritis: a double-blind, randomized controlled trial. J Am Coll Nutr. 2017;36(1):9–15. doi:10.1080/07315724.2016.114009327710596
  • Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022–1023. doi:10.1038/4441022a17183309
  • Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–484. doi:10.1038/nature0754019043404
  • Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–1031. doi:10.1038/nature0541417183312
  • Andoh A, Nishida A, Takahashi K, et al. Comparison of the gut microbial community between obese and lean peoples using 16S gene sequencing in a Japanese population. J Clin Biochem Nutr. 2016;59(1):65–70. doi:10.3164/jcbn.15-15227499582
  • Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180. doi:10.1038/nature0994421508958
  • Jonsson AL, Bäckhed F. Role of gut microbiota in atherosclerosis. Nat Rev Cardiol. 2017;14(2):79–87. doi:10.1038/nrcardio.2016.18327905479
  • Wu M, Yang S, Wang S, et al. Effect of berberine on atherosclerosis and gut microbiota modulation and their correlation in high-fat diet-fed ApoE-/- mice. Front Pharmacol. 2020;11:223. doi:10.3389/fphar.2020.0022332231564
  • Etxeberria U, Arias N, Boque N, et al. 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. doi:10.1016/j.jnutbio.2015.01.00225762527
  • Zhao L, Zhang Q, Ma W, et al. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food Funct. 2017;8(12):4644–4656. doi:10.1039/c7fo01383c29152632
  • Lin R, Piao M, Song Y. Dietary quercetin increases colonic microbial diversity and attenuates colitis severity in Citrobacter rodentium-infected mice. Front Microbiol. 2019;10:1092. doi:10.3389/fmicb.2019.0109231156598
  • Kawabata K, Sugiyama Y, Sakano T, Ohigashi H. Flavonols enhanced production of anti-inflammatory substance(s) by Bifidobacterium adolescentis: prebiotic actions of galangin, quercetin, and fisetin. Biofactors. 2013;39(4):422–429. doi:10.1002/biof.108123554103
  • Kawabata K, Baba N, Sakano T, et al. Functional properties of anti-inflammatory substances from quercetin-treated Bifidobacterium adolescentis. Biosci Biotechnol Biochem. 2018;82(4):689–697. doi:10.1080/09168451.2017.140191629165050
  • Porras D, Nistal E, Martinez-Florez S, et al. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radic Biol Med. 2017;102:188–202. doi:10.1016/j.freeradbiomed.2016.11.03727890642
  • Nie J, Zhang L, Zhao G, Du X. Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites. J Appl Microbiol. 2019;127(6):1824–1834. doi:10.1111/jam.1444131509634
  • Bird A. Perceptions of epigenetics. Nature. 2007;447(7143):396–398. doi:10.1038/nature0591317522671
  • Nagase H, Ghosh S. Epigenetics: differential DNA methylation in mammalian somatic tissues. FEBS J. 2008;275(8):1617–1623. doi:10.1111/j.1742-4658.2008.06330.x18331347
  • Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–297. doi:10.1016/s0092-8674(04)00045-514744438
  • Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3(6):415–428. doi:10.1038/nrg81612042769
  • Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31(1):27–36. doi:10.1093/carcin/bgp22019752007
  • Busch C, Burkard M, Leischner C, et al. Epigenetic activities of flavonoids in the prevention and treatment of cancer. Clin Epigenetics. 2015;7:64. doi:10.1186/s13148-015-0095-z26161152
  • Carlos-Reyes A, Lopez-Gonzalez JS, Meneses-Flores M, et al. Dietary compounds as epigenetic modulating agents in cancer. Front Genet. 2019;10:79. doi:10.3389/fgene.2019.0007930881375
  • Park S, Lim W, Bazer FW, et al. Quercetin inhibits proliferation of endometriosis regulating cyclin D1 and its target microRNAs in vitro and in vivo. J Nutr Biochem. 2019;63:87–100. doi:10.1016/j.jnutbio.2018.09.02430359864
  • Zheng NG, Wang JL, Yang SL, Wu JL. Aberrant epigenetic alteration in Eca9706 cells modulated by nanoliposomal quercetin combined with butyrate mediated via epigenetic-NF-kappaB signaling. Asian Pac J Cancer Prev. 2014;15(11):4539–4543. doi:10.7314/apjcp.2014.15.11.453924969881
  • Lee WJ, Chen YR, Tseng TH. Quercetin induces FasL-related apoptosis, in part, through promotion of histone H3 acetylation in human leukemia HL-60 cells. Oncol Rep. 2011;25(2):583–591. doi:10.3892/or.2010.109721165570
  • Devarshi PP, Jones AD, Taylor EM, et al. Quercetin and quercetin-rich red onion extract alter Pgc-1alpha promoter methylation and splice variant expression. PPAR Res. 2017;2017:3235693. doi:10.1155/2017/323569328191013
  • Liu CM, Ma JQ, Xie WR, et al. Quercetin protects mouse liver against nickel-induced DNA methylation and inflammation associated with the Nrf2/HO-1 and p38/STAT1/NF-kappaB pathway. Food Chem Toxicol. 2015;82:19–26. doi:10.1016/j.fct.2015.05.00125957741
  • Bol VV, Reusens BM, Remacle CA. Postnatal catch-up growth after fetal protein restriction programs proliferation of rat preadipocytes. Obesity. 2008;16(12):2760–2763. doi:10.1038/oby.2008.41718833213
  • Victora CG, Adair L, Fall C, et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008;371(9609):340–357. doi:10.1016/S0140-6736(07)61692-418206223
  • Sharkey D, Gardner DS, Fainberg HP, et al. Maternal nutrient restriction during pregnancy differentially alters the unfolded protein response in adipose and renal tissue of obese juvenile offspring. FASEB J. 2009;23(5):1314–1324. doi:10.1096/fj.08-11433019103646
  • Luyckx VA, Brenner BM. Birth weight, malnutrition and kidney-associated outcomes–a global concern. Nat Rev Nephrol. 2015;11(3):135–149. doi:10.1038/nrneph.2014.25125599618
  • Wankhade UD, Zhong Y, Kang P, et al. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations. PLoS One. 2017;12(4):e0175675. doi:10.1371/journal.pone.017567528414763
  • Uchiyama R, Kupkova K, Shetty SJ, et al. Histone H3 lysine 4 methylation signature associated with human undernutrition. Proc Natl Acad Sci USA. 2018;115(48):E11264–E11273. doi:10.1073/pnas.172212511530420518
  • Sato S, Mukai Y, Saito T. Quercetin intake during lactation modulates the AMP-activated protein kinase pathway in the livers of adult male rat offspring programmed by maternal protein restriction. J Nutr Biochem. 2013;24(1):118–123. doi:10.1016/j.jnutbio.2012.03.00722819550
  • Jiang S, Teague AM, Tryggestad JB, et al. Role of metformin in epigenetic regulation of placental mitochondrial biogenesis in maternal diabetes. Sci Rep. 2020;10(1):8314. doi:10.1038/s41598-020-65415-032433500
  • Wu Z, Zhao J, Xu H, et al. Maternal quercetin administration during gestation and lactation decrease endoplasmic reticulum stress and related inflammation in the adult offspring of obese female rats. Eur J Nutr. 2014;53(8):1669–1683. doi:10.1007/s00394-014-0673-424570028
  • Vanhees K, Godschalk RW, Sanders A, et al. Maternal quercetin intake during pregnancy results in an adapted iron homeostasis at adulthood. Toxicology. 2011;290(2–3):350–358. doi:10.1016/j.tox.2011.10.01722064046
  • Nicolucci AC, Hume MP, Martinez I, et al. Prebiotics reduce body fat and alter intestinal microbiota in children who are overweight or with obesity. Gastroenterology. 2017;153(3):711–722. doi:10.1053/j.gastro.2017.05.05528596023