The roles of quercetin in diabetes mellitus and related metabolic disorders; special focus on the modulation of gut microbiota: A comprehensive review

References

• Alrawaiq, N. S., and A. Abdullah. 2014. A review of flavonoid quercetin: Metabolism, bioactivity and antioxidant properties. International Journal of PharmTech Research 6 (3):933–41.
   Google Scholar
• Aranaz, P., M. Zabala, A. Romo-Hualde, D. Navarro-Herrera, M. López-Yoldi, J. L. Vizmanos, J. A. Martínez, F. I. Milagro, and C. J. González-Navarro. 2020. A combination of borage seed oil and quercetin reduces fat accumulation and improves insulin sensitivity in obese rats. Food & Function 11 (5):4512–24. doi: 10.1039/d0fo00504e.
   PubMed Web of Science ®Google Scholar
• Azuma, K., K. Ippoushi, H. Ito, H. Horie, and J. Terao. 2003. Enhancing effect of lipids and emulsifiers on the accumulation of quercetin metabolites in blood plasma after the short-term ingestion of onion by rats. Bioscience, Biotechnology, and Biochemistry 67 (12):2548–55. doi: 10.1271/bbb.67.2548.
   PubMed Web of Science ®Google Scholar
• Bai, L., X. Li, L. He, Y. Zheng, H. Lu, J. Li, L. Zhong, R. Tong, Z. Jiang, J. Shi, et al. 2019. Antidiabetic potential of flavonoids from traditional Chinese medicine: A review. The American Journal of Chinese Medicine 47 (5):933–57. doi: 10.1142/S0192415X19500496.
   PubMed Web of Science ®Google Scholar
• Ballali, S., and F. Lanciai. 2012. Functional food and diabetes: A natural way in diabetes prevention? International Journal of Food Sciences and Nutrition 63 (supp1):51–61. doi: 10.3109/09637486.2011.637487.
   PubMedGoogle Scholar
• Ballmann, C., T. Denney, R. J. Beyers, T. Quindry, M. Romero, J. T. Selsby, and J. C. Quindry. 2017. Long-term dietary quercetin enrichment as a cardioprotective countermeasure in MDX mice . Experimental Physiology 102 (6):635–49. doi: 10.1113/EP086091.
   PubMed Web of Science ®Google Scholar
• Bekkering, P., I. Jafri, F. J. van Overveld, and G. T. Rijkers. 2013. The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes. Expert Review of Clinical Immunology 9 (11):1031–41. doi: 10.1586/1744666X.2013.848793.
   PubMed Web of Science ®Google Scholar
• Belforte, F. S., N. Fernandez, F. Tonín Monzón, A. D. Rosso, S. Quesada, M. C. Cimolai, A. Millán, G. E. Cerrone, G. D. Frechtel, R. Burcelin, et al. 2019. Getting to know the gut microbial diversity of metropolitan Buenos Aires inhabitants. Frontiers in Microbiology 10:965. doi: 10.3389/fmicb.2019.00965.
   PubMed Web of Science ®Google Scholar
• Bentz, A. B. 2017. A review of quercetin: Chemistry, antioxident properties, and bioavailability. Journal of Young Investigators. Accessed on September 27, 2021. https://www.jyi.org/2009-april/2017/10/15/a-review-of-quercetinchemistry-antioxidant-properties-and-bioavailability.
   PubMedGoogle Scholar
• Cani, P. D., and N. M. Delzenne. 2011. The gut microbiome as therapeutic target. Pharmacology & Therapeutics 130 (2):202–12. doi: 10.1016/j.pharmthera.2011.01.012.
   PubMed Web of Science ®Google Scholar
• Cermak, R., S. Landgraf, and S. Wolffram. 2003. The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. The Journal of Nutrition 133 (9):2802–7. doi: 10.1093/jn/133.9.2802.
   PubMed Web of Science ®Google Scholar
• Cerreti, M., K. Liburdi, F. Del Franco, and M. Esti. 2020. Heat and light stability of natural yellow colourants in model beverage ­systems. Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment 37 (6):905–15. doi: 10.1080/19440049.2020.1744739.
   PubMed Web of Science ®Google Scholar
• Chen, C., J. Zhou, and C. Ji. 2010. Quercetin: A potential drug to reverse multidrug resistance. Life Sciences 87 (11–12):333–8. doi: 10.1016/j.lfs.2010.07.004.
   PubMed Web of Science ®Google Scholar
• Chen, C., J. Huang, J. Shen, and Q. Bai. 2019. Quercetin improves endothelial insulin sensitivity in obese mice by inhibiting Drp1 phosphorylation at serine 616 and mitochondrial fragmentation. Acta Biochimica et Biophysica Sinica 51 (12):1250–7. doi: 10.1093/abbs/gmz127.
   PubMed Web of Science ®Google Scholar
• Chen, S., H. Jiang, X. Wu, and J. Fang. 2016. Therapeutic effects of quercetin on inflammation, obesity, and type 2 diabetes. Mediators of Inflammation 2016:9340637. doi: 10.1155/2016/9340637.
   PubMed Web of Science ®Google Scholar
• Choi, H.-J., J.-H. Kim, C.-H. Lee, Y.-J. Ahn, J.-H. Song, S.-H. Baek, and D.-H. Kwon. 2009. Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus. Antiviral Research 81 (1):77–81. doi: 10.1016/j.antiviral.2008.10.002.
   PubMed Web of Science ®Google Scholar
• Choi, H.-N., S.-M. Jeong, G. H. Huh, and J.-I. Kim. 2015. Quercetin ameliorates insulin sensitivity and liver steatosis partly by increasing adiponectin expression in ob/ob mice. Food Science and Biotechnology 24 (1):273–9. doi: 10.1007/s10068-015-0036-9.
   Web of Science ®Google Scholar
• Choudhury, H., M. Pandey, C. K. Hua, C. S. Mun, J. K. Jing, L. Kong, L. Y. Ern, N. A. Ashraf, S. W. Kit, T. S. Yee, et al. 2018. An update on natural compounds in the remedy of diabetes mellitus: A systematic review. Journal of Traditional and Complementary Medicine 8 (3):361–76. doi: 10.1016/j.jtcme.2017.08.012.
   PubMedGoogle Scholar
• Cowan, S. F., E. R. Leeming, A. Sinclair, A. L. Dordevic, H. Truby, and S. J. Gibson. 2020. Effect of whole foods and dietary patterns on markers of subclinical inflammation in weight-stable overweight and obese adults: A systematic review. Nutrition Reviews 78 (1):19–38. doi: 10.1093/nutrit/nuz030.
   PubMed Web of Science ®Google Scholar
• Dall’Acqua, S., G. Miolo, G. Innocenti, and S. Caffieri. 2012. The photodegradation of quercetin: Relation to oxidation. Molecules (Basel, Switzerland) 17 (8):8898–907. doi: 10.3390/molecules17088898.
   PubMed Web of Science ®Google Scholar
• Daniel, O. O., A. O. Adeoye, J. Ojowu, and O. O. Olorunsogo. 2018. Inhibition of liver mitochondrial membrane permeability transition pore opening by quercetin and vitamin E in streptozotocin-induced diabetic rats. Biochemical and Biophysical Research Communications 504 (2):460–9. doi: 10.1016/j.bbrc.2018.08.114.
   PubMed Web of Science ®Google Scholar
• Darband, S. G., M. Kaviani, B. Yousefi, S. Sadighparvar, F. G. Pakdel, J. A. Attari, I. Mohebbi, S. Naderi, and M. Majidinia. 2018. Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer. Journal of Cellular Physiology 233 (9):6544–60. doi: 10.1002/jcp.26595.
   PubMed Web of Science ®Google Scholar
• Dehghani, F., M. Morvaridzadeh, A. B. Pizarro, T. Rouzitalab, M. Khorshidi, A. Izadi, F. Shidfar, A. Omidi, and J. Heshmati. 2021. Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD 31 (7):1953–61. doi: 10.1016/j.numecd.2021.02.017.
   PubMed Web of Science ®Google Scholar
• Dewanjee, S., P. Chakraborty, B. Mukherjee, and V. De Feo. 2020. Plant-based antidiabetic nanoformulations: The emerging paradigm for effective therapy. International Journal of Molecular Sciences 21 (6):2217. doi: 10.3390/ijms21062217.
   PubMed Web of Science ®Google Scholar
• Dhanya, R., and C. Kartha. 2021. Quercetin improves oxidative stress-induced pancreatic beta cell alterations via mTOR-signaling. Molecular and Cellular Biochemistry:1–9. doi: 10.1007/s11010-021-04193-3.
   Web of Science ®Google Scholar
• Dillard, C. J., and J. B. German. 2000. Phytochemicals: Nutraceuticals and human health. Journal of the Science of Food and Agriculture 80 (12):1744–56. doi: 10.1002/1097-0010(20000915)80:12<1744::AID-JSFA725>3.0.CO;2-W.
   Web of Science ®Google Scholar
• Dower, J. I., J. M. Geleijnse, L. Gijsbers, P. L. Zock, D. Kromhout, and P. C. Hollman. 2015. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: A randomized, double-blind, placebo-controlled, crossover trial. The American Journal of Clinical Nutrition 101 (5):914–21. doi: 10.3945/ajcn.114.098590.
   PubMed Web of Science ®Google Scholar
• Du, L., M. Hao, C. Li, W. Wu, W. Wang, Z. Ma, T. Yang, N. Zhang, A. T. Isaac, X. Zhu, et al. 2017. Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high-glucose-cultured lens, and SRA01/04 cells through transforming growth factor-β2/phosphoinositide 3-kinase/AKT pathway. Molecular and Cellular Endocrinology 452:44–56. doi: 10.1016/j.mce.2017.05.011.
   PubMed Web of Science ®Google Scholar
• Ebrahimpour, S., M. Zakeri, and A. Esmaeili. 2020. Crosstalk between obesity, diabetes, and Alzheimer’s disease: Introducing quercetin as an effective triple herbal medicine. Ageing Research Reviews 62:101095. doi: 10.1016/j.arr.2020.101095.
   PubMed Web of Science ®Google Scholar
• Egert, S., A. Bosy-Westphal, J. Seiberl, C. Kürbitz, U. Settler, S. Plachta-Danielzik, A. E. Wagner, J. Frank, J. Schrezenmeir, G. Rimbach, et al. 2009. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: A double-blinded, placebo-controlled cross-over study. British Journal of Nutrition 102 (7):1065–74. doi: 10.1017/S0007114509359127.
   PubMed Web of Science ®Google Scholar
• Egert, S., S. Wolffram, A. Bosy-Westphal, C. Boesch-Saadatmandi, A. E. Wagner, J. Frank, G. Rimbach, and M. J. Mueller. 2008. Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. The Journal of Nutrition 138 (9):1615–21. doi: 10.1093/jn/138.9.1615.
   PubMed Web of Science ®Google Scholar
• Egert, S., S. Wolffram, B. Schulze, P. Langguth, E. M. Hubbermann, K. Schwarz, B. Adolphi, A. Bosy-Westphal, G. Rimbach, and M. J. Müller. 2012. Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules. The British Journal of Nutrition 107 (4):539–46. doi: 10.1017/S0007114511003242.
   PubMed Web of Science ®Google Scholar
• Eid, H. M., and P. S. Haddad. 2017. The antidiabetic potential of quercetin: Underlying mechanisms. Current Medicinal Chemistry 24 (4):355–64. doi: 10.2174/0929867323666160909153707.
   PubMed Web of Science ®Google Scholar
• Eitah, H. E., Y. A. Maklad, N. F. Abdelkader, A. A. G. el Din, M. A. Badawi, and S. A. Kenawy. 2019. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicology and Applied Pharmacology 365:30–40. doi: 10.1016/j.taap.2018.12.011.
   PubMed Web of Science ®Google Scholar
• Etxeberria, U., N. Arias, N. Boqué, M. T. Macarulla, M. P. Portillo, J. A. Martínez, and F. I. Milagro. 2015. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. The Journal of Nutritional Biochemistry 26 (6):651–60. doi: 10.1016/j.jnutbio.2015.01.002.
   PubMed Web of Science ®Google Scholar
• Farsi, F., J. Heshmati, A. Keshtkar, P. Irandoost, N. M. Alamdari, A. Akbari, L. Janani, N. Morshedzadeh, and M. Vafa. 2019. Can coenzyme Q10 supplementation effectively reduce human tumor necrosis factor-α and interleukin-6 levels in chronic inflammatory diseases? A systematic review and meta-analysis of randomized controlled trials. Pharmacological Research 148:104290. doi: 10.1016/j.phrs.2019.104290.
   PubMed Web of Science ®Google Scholar
• Formica, J., and W. Regelson. 1995. Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 33 (12):1061–80. doi: 10.1016/0278-6915(95)00077-1.
   PubMed Web of Science ®Google Scholar
• Fortunato, L. R., C. F. Alves, M. M. Teixeira, and A. P. Rogerio. 2012. Quercetin: A flavonoid with the potential to treat asthma. Brazilian Journal of Pharmaceutical Sciences 48 (4):589–99. doi: 10.1590/S1984-82502012000400002.
   Web of Science ®Google Scholar
• Fuleki, T., and J. M. Ricardo-da-Silva. 2003. Effects of cultivar and processing method on the contents of catechins and procyanidins in grape juice. Journal of Agricultural and Food Chemistry 51 (3):640–6. doi: 10.1021/jf020689m.
   PubMed Web of Science ®Google Scholar
• Gandhi, G. R., A. B. S. Vasconcelos, D.-T. Wu, H.-B. Li, P. J. Antony, H. Li, et al. 2020. Citrus flavonoids as promising phytochemicals targeting diabetes and related complications: A systematic review of in vitro and in vivo studies. Nutrients 12 (10):2907. doi: 10.3390/nu12102907.
   PubMed Web of Science ®Google Scholar
• Gansukh, E., A. Nile, D. H. Kim, J. W. Oh, and S. H. Nile. 2021. New insights into antiviral and cytotoxic potential of quercetin and its derivatives–A biochemical perspective. Food Chemistry 334:127508. doi: 10.1016/j.foodchem.2020.127508.
   PubMed Web of Science ®Google Scholar
• Ghaffari, S., and N. Roshanravan. 2020. The role of nutraceuticals in prevention and treatment of hypertension: An updated review of the literature. Food Research International (Ottawa, ON) 128:108749. doi: 10.1016/j.foodres.2019.108749.
   PubMed Web of Science ®Google Scholar
• Ghavami, A., N. Roshanravan, S. Alipour, M. Barati, B. Mansoori, F. Ghalichi, E. Nattagh- Eshtivan, and A. Ostadrahimi. 2018. Assessing the effect of high performance inulin supplementation via KLF5 mRNA expression in adults with type 2 diabetes: A randomized placebo controlled clinical trail. Advanced Pharmaceutical Bulletin 8 (1):39–47. doi: 10.15171/apb.2018.005.
   PubMed Web of Science ®Google Scholar
• Ghimire, S., S. Wongkuna, R. Sankaranarayanan, E. P. Ryan, G. J. Bhat, and J. Scaria. 2020. Rice bran and quercetin produce a positive synergistic effect on human gut microbiota, elevate the level of propionate, and reduce the population of enterobacteriaceae family when determined using a bioreactor model. BioRxiv. Preprinted. doi: 10.1101/2020.02.13.947515.
   Google Scholar
• Ghorbani, A., R. Rashidi, and R. Shafiee-Nick. 2019. Flavonoids for preserving pancreatic beta cell survival and function: A mechanistic review. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 111:947–57. doi: 10.1016/j.biopha.2018.12.127.
   PubMed Web of Science ®Google Scholar
• Gil-Cardoso, K., I. Ginés, M. Pinent, A. Ardévol, M. Blay, and X. Terra. 2016. Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity. Nutrition Research Reviews 29 (2):234–48. doi: 10.1017/S0954422416000159.
   PubMed Web of Science ®Google Scholar
• Glovaci, D., W. Fan, and N. D. Wong. 2019. Epidemiology of diabetes mellitus and cardiovascular disease. Current Cardiology Reports 21 (4):21. doi: 10.1007/s11886-019-1107-y.
   PubMed Web of Science ®Google Scholar
• Gomes, J. M. G., J. de Assis Costa, and R. C. G. Alfenas. 2017. Metabolic endotoxemia and diabetes mellitus: A systematic review. Metabolism: Clinical and Experimental 68:133–44. doi: 10.1016/j.metabol.2016.12.009.
   PubMed Web of Science ®Google Scholar
• Guo, Y., and R. S. Bruno. 2015. Endogenous and exogenous mediators of quercetin bioavailability. The Journal of Nutritional Biochemistry 26 (3):201–10. doi: 10.1016/j.jnutbio.2014.10.008.
   PubMed Web of Science ®Google Scholar
• Guo, Y., E. Mah, C. G. Davis, T. Jalili, M. G. Ferruzzi, O. K. Chun, and R. S. Bruno. 2013. Dietary fat increases quercetin bioavailability in overweight adults. Molecular Nutrition & Food Research 57 (5):896–905. doi: 10.1002/mnfr.201200619.
   PubMed Web of Science ®Google Scholar
• Haenen, G. R., J. B. Paquay, R. E. Korthouwer, and A. Bast. 1997. Peroxynitrite scavenging by flavonoids. Biochemical and Biophysical Research Communications 236 (3):591–3. doi: 10.1006/bbrc.1997.7016.
   PubMed Web of Science ®Google Scholar
• Haleagrahara, N., K. Hodgson, S. Miranda-Hernandez, S. Hughes, A. B. Kulur, and N. Ketheesan. 2018. Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis. Inflammopharmacology 26 (5):1219–32. doi: 10.1007/s10787-018-0464-2.
   PubMed Web of Science ®Google Scholar
• Han, R.-M., J.-P. Zhang, and L. H. Skibsted. 2012. Reaction dynamics of flavonoids and carotenoids as antioxidants. Molecules (Basel, Switzerland) 17 (2):2140–60. doi: 10.3390/molecules17022140.
   PubMed Web of Science ®Google Scholar
• Harishkumar, R., L. P. K. Reddy, S. H. Karadkar, M. A. Murad, S. S. Karthik, S. Manigandan, C. I. Selvaraj, and J. G. Christopher. 2019. Toxicity and selective biochemical assessment of quercetin, gallic acid, and curcumin in zebrafish. Biological & Pharmaceutical Bulletin 42 (12):1969–76. doi: 10.1248/bpb.b19-00296.
   PubMed Web of Science ®Google Scholar
• He, C., Y. Shan, and W. Song. 2015. Targeting gut microbiota as a possible therapy for diabetes. Nutrition Research (New York, NY) 35 (5):361–7. doi: 10.1016/j.nutres.2015.03.002.
   PubMed Web of Science ®Google Scholar
• Huang, H., D. Liao, Y. Dong, and R. Pu. 2019. Clinical effectiveness of quercetin supplementation in the management of weight loss: A pooled analysis of randomized controlled trials. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 12:553–63. doi: 10.2147/DMSO.S199830.
   PubMed Web of Science ®Google Scholar
• Iskender, H., E. Dokumacioglu, T. M. Sen, I. Ince, Y. Kanbay, and S. Saral. 2017. The effect of hesperidin and quercetin on oxidative stress, NF-κB and SIRT1 levels in a STZ-induced experimental diabetes model. Biomedicine & Pharmacotherapy 90:500–8. doi: 10.1016/j.biopha.2017.03.102.
   PubMed Web of Science ®Google Scholar
• Ivey, K. L., M. K. Jensen, J. M. Hodgson, A. H. Eliassen, A. Cassidy, and E. B. Rimm. 2017. Association of flavonoid-rich foods and flavonoids with risk of all-cause mortality. British Journal of Nutrition 117 (10):1470–7. doi: 10.1017/S0007114517001325.
   PubMed Web of Science ®Google Scholar
• Jayachandran, M., T. Zhang, K. Ganesan, B. Xu, and S. S. M. Chung. 2018. Isoquercetin ameliorates hyperglycemia and regulates key enzymes of glucose metabolism via insulin signaling pathway in streptozotocin-induced diabetic rats. European Journal of Pharmacology 829:112–20. doi: 10.1016/j.ejphar.2018.04.015.
   PubMed Web of Science ®Google Scholar
• Jeong, S. M., M. J. Kang, H. N. Choi, J. H. Kim, and J. I. Kim. 2012. Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic DB/DB mice. Nutrition Research and Practice 6 (3):201–7. doi: 10.4162/nrp.2012.6.3.201.
   PubMed Web of Science ®Google Scholar
• Jiang, H., Y. Horiuchi, K-y Hironao, T. Kitakaze, Y. Yamashita, and H. Ashida. 2020. Prevention effect of quercetin and its glycosides on obesity and hyperglycemia through activating AMPKα in high-fat diet-fed ICR mice. Journal of Clinical Biochemistry and Nutrition 67 (1):74. doi: 10.3164/jcbn.20-47.
   PubMed Web of Science ®Google Scholar
• Jiao, Y., L. Wu, N. D. Huntington, and X. Zhang. 2020. Crosstalk between gut microbiota and innate immunity and its implication in autoimmune diseases. Frontiers in Immunology 11:282. doi: 10.3389/fimmu.2020.00282.
   PubMed Web of Science ®Google Scholar
• Jin, S., J. Liu, Y. Jia, T. Han, X. Zhao, C. Sun, and L. Na. 2021. The association of dietary flavonoids, magnesium and their interactions with the metabolic syndrome in Chinese adults: A prospective cohort study. British Journal of Nutrition 126 (6):892. doi: 10.1017/S0007114520004754.
   PubMed Web of Science ®Google Scholar
• Joshi, T., A. K. Singh, P. Haratipour, A. N. Sah, A. K. Pandey, R. Naseri, V. Juyal, and M. H. Farzaei. 2019. Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications. Journal of Cellular Physiology 234 (10):17212–31. doi: 10.1002/jcp.28528.
   PubMed Web of Science ®Google Scholar
• Ju, S., Y. Ge, P. Li, X. Tian, H. Wang, X. Zheng, and S. Ju. 2018. Dietary quercetin ameliorates experimental colitis in mouse by remodeling the function of colonic macrophages via a heme oxygenase-1-dependent pathway. Cell Cycle (Georgetown, Tex.) 17 (1):53–63. doi: 10.1080/15384101.2017.1387701.
   PubMed Web of Science ®Google Scholar
• Justino, G. C., M. R. Santos, S. Canário, C. Borges, M. H. Florêncio, and L. Mira. 2004. Plasma quercetin metabolites: Structure–antioxidant activity relationships. Archives of Biochemistry and Biophysics 432 (1):109–21. doi: 10.1016/j.abb.2004.09.007.
   PubMed Web of Science ®Google Scholar
• Kabera, J. N., E. Semana, A. R. Mussa, and X. He. 2014. Plant secondary metabolites: Biosynthesis, classification, function and pharmacological properties. Journal of Pharmacy and Pharmacology 2 (7):377–92.
   Google Scholar
• Khan, S., and G. Jena. 2015. The role of butyrate, a histone deacetylase inhibitor in diabetes mellitus: Experimental evidence for therapeutic intervention. Epigenomics 7 (4):669–80. doi: 10.2217/epi.15.20.
   PubMed Web of Science ®Google Scholar
• Khodarahmi, A., A. Eshaghian, F. Safari, and A. Moradi. 2019. Quercetin mitigates hepatic insulin resistance in rats with bile duct ligation through modulation of the STAT3/SOCS3/IRS1 signaling pathway. Journal of Food Science 84 (10):3045–53. doi: 10.1111/1750-3841.14793.
   PubMed Web of Science ®Google Scholar
• Khorshidi, M., A. Moini, E. Alipoor, N. Rezvan, S. Gorgani-Firuzjaee, M. Yaseri, and M. J. Hosseinzadeh-Attar. 2018. The effects of quercetin supplementation on metabolic and hormonal parameters as well as plasma concentration and gene expression of resistin in overweight or obese women with polycystic ovary syndrome. Phytotherapy Research 32 (11):2282–9. doi: 10.1002/ptr.6166.
   PubMed Web of Science ®Google Scholar
• Kobori, M. 2014. Dietary quercetin and other polyphenols: Attenuation of obesity. In Polyphenols in human health and disease, 163–75. USA: Academic press.
   Google Scholar
• Kumar, R., S. Vijayalakshmi, and S. Nadanasabapathi. 2017. Health benefits of quercetin. Defence Life Science Journal 2 (2):142–51. doi: 10.14429/dlsj.2.11359.
   Google Scholar
• Larsen, N., F. K. Vogensen, F. W. J. van den Berg, D. S. Nielsen, A. S. Andreasen, B. K. Pedersen, W. A. Al-Soud, S. J. Sørensen, L. H. Hansen, M. Jakobsen, et al. 2010. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PloS One 5 (2):e9085. doi: 10.1371/journal.pone.0009085.
   PubMed Web of Science ®Google Scholar
• Latos‐Brozio, M., and A. Masek. 2019. Structure-activity relationships analysis of monomeric and polymeric polyphenols (quercetin, rutin and catechin) obtained by various polymerization methods . Chemistry & Biodiversity 16 (12):e1900426. doi: 10.1002/cbdv.201900426.
   PubMed Web of Science ®Google Scholar
• Li, H., L. Xiao, H. He, H. Zeng, J. Liu, C. Jiang, G. Mei, J. Yu, H. Chen, P. Yao, et al. 2021. Quercetin attenuates atherosclerotic inflammation by inhibiting galectin-3-NLRP3 signaling pathway . Molecular Nutrition & Food Research 65 (15):e2000746. doi: 10.1002/mnfr.202000746.
   PubMed Web of Science ®Google Scholar
• Lin, C.-F., Y.-L. Leu, S. A. Al-Suwayeh, M.-C. Ku, T.-L. Hwang, and J.-Y. Fang. 2012. Anti-inflammatory activity and percutaneous absorption of quercetin and its polymethoxylated compound and glycosides: The relationships to chemical structures. European Journal of Pharmaceutical Sciences : official Journal of the European Federation for Pharmaceutical Sciences 47 (5):857–64. doi: 10.1016/j.ejps.2012.04.024.
   PubMed Web of Science ®Google Scholar
• Lin, R., M. Piao, and Y. Song. 2019. Dietary quercetin increases colonic microbial diversity and attenuates colitis severity in Citrobacter rodentium-infected mice. Frontiers in Microbiology 10:1092. doi: 10.3389/fmicb.2019.01092.
   PubMed Web of Science ®Google Scholar
• Lv, M., S. Yang, L. Cai, L. Q. Qin, B. Y. Li, and Z. Wan. 2018. Effects of quercetin intervention on cognition function in APP/PS1 mice was affected by vitamin D status. Molecular Nutrition & Food Research 62 (24):e1800621. doi: 10.1002/mnfr.201800621.
   PubMed Web of Science ®Google Scholar
• M, S. S., and D. N. C. 2017. Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 94:605–11.
   PubMed Web of Science ®Google Scholar
• Manach, C., C. Morand, V. Crespy, C. Demigné, O. Texier, F. Régérat, and C. Rémésy. 1998. Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties. FEBS Letters 426 (3):331–6. doi: 10.1016/s0014-5793(98)00367-6.
   PubMed Web of Science ®Google Scholar
• Mauricio, D., N. Alonso, and M. Gratacòs. 2020. Chronic diabetes complications: The need to move beyond classical concepts. Trends in Endocrinology and Metabolism: TEM 31 (4):287–95. doi: 10.1016/j.tem.2020.01.007.
   PubMed Web of Science ®Google Scholar
• Mendoza, M. P. G. 2020. Enrichment of vegetable oils with phenolic antioxidants for food applications. France: Université de Bordeaux.
   Google Scholar
• Mohammad, A., V. Sharma, and J. H. McNeill. 2002. Vanadium increases GLUT4 in diabetic rat skeletal muscle. Molecular and Cellular Biochemistry 233 (1-2):139–43. doi: 10.1023/A:1015558328757.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay, P., S. Maity, S. Mandal, A. S. Chakraborti, A. Prajapati, and P. Kundu. 2018. Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment. Carbohydrate Polymers 182:42–51. doi: 10.1016/j.carbpol.2017.10.098.
   PubMed Web of Science ®Google Scholar
• Munhoz, A., and T. S. Frode. 2018. Isolated compounds from natural products with potential antidiabetic activity-A systematic review. Current Diabetes Reviews 14 (1):36–106.
   PubMed Web of Science ®Google Scholar
• Murakami, M., T. Yamaguchi, H. Takamura, and T. Atoba. 2004. Effects of thermal treatment on radical‐scavenging activity of single and mixed polyphenolic compounds. Journal of Food Science 69 (1):FCT7–FCT10. doi: 10.1111/j.1365-2621.2004.tb17848.x.
   Web of Science ®Google Scholar
• Murota, K., and J. Terao. 2003. Antioxidative flavonoid quercetin: Implication of its intestinal absorption and metabolism. Archives of Biochemistry and Biophysics 417 (1):12–7. doi: 10.1016/s0003-9861(03)00284-4.
   PubMed Web of Science ®Google Scholar
• Murri, M., I. Leiva, J. M. Gomez-Zumaquero, F. J. Tinahones, F. Cardona, F. Soriguer, and M. I. Queipo-Ortuño. 2013. Gut microbiota in children with type 1 diabetes differs from that in healthy children: A case-control study. BMC Medicine 11:46. doi: 10.1186/1741-7015-11-46.
   PubMed Web of Science ®Google Scholar
• Neisy, A., F. Zal, A. Seghatoleslam, and S. Alaee. 2019. Amelioration by quercetin of insulin resistance and uterine GLUT4 and ERα gene expression in rats with polycystic ovary syndrome (PCOS). Reproduction, Fertility, and Development 31 (2):315–23. doi: 10.1071/RD18222.
   PubMed Web of Science ®Google Scholar
• Nie, J., L. Zhang, G. Zhao, and X. Du. 2019. Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites. Journal of Applied Microbiology 127 (6):1824–34. doi: 10.1111/jam.14441.
   PubMed Web of Science ®Google Scholar
• Nishimuro, H., H. Ohnishi, M. Sato, M. Ohnishi-Kameyama, I. Matsunaga, S. Naito, K. Ippoushi, H. Oike, T. Nagata, H. Akasaka, et al. 2015. Estimated daily intake and seasonal food sources of quercetin in Japan. Nutrients 7 (4):2345–58. doi: 10.3390/nu7042345.
   PubMed Web of Science ®Google Scholar
• Ostadmohammadi, V., A. Milajerdi, E. Ayati, F. Kolahdooz, and Z. Asemi. 2019. Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta‐analysis of randomized controlled trials. Phytotherapy Research 33 (5):1330–40. doi: 10.1002/ptr.6334.
   PubMed Web of Science ®Google Scholar
• Panchal, S. K., H. Poudyal, and L. Brown. 2012. Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. The Journal of Nutrition 142 (6):1026–32. doi: 10.3945/jn.111.157263.
   PubMed Web of Science ®Google Scholar
• Peng, J., Q. Li, K. Li, L. Zhu, X. Lin, X. Lin, Q. Shen, G. Li, and X. Xie. 2017. Quercetin improves glucose and lipid metabolism of diabetic rats: Involvement of AKT signaling and SIRT1. Journal of Diabetes Research 2017:3417306. doi: 10.1155/2017/3417306.
   PubMed Web of Science ®Google Scholar
• Peng, L., Q. Zhang, Y. Zhang, Z. Yao, P. Song, L. Wei, G. Zhao, and Z. Yan. 2020. Effect of tartary buckwheat, rutin, and quercetin on lipid metabolism in rats during high dietary fat intake. Food Science & Nutrition 8 (1):199–213. doi: 10.1002/fsn3.1291.
   PubMed Web of Science ®Google Scholar
• Pereira, T. M. C., F. S. Pimenta, M. L. Porto, M. P. Baldo, B. P. Campagnaro, and A. L. Gava. 2016. Coadjuvants in the diabetic complications: Nutraceuticals and drugs with pleiotropic effects. International Journal of Molecular Sciences 17 (8):1273. doi: 10.3390/ijms17081273.
   PubMed Web of Science ®Google Scholar
• Porras, D., E. Nistal, S. Martínez-Flórez, S. Pisonero-Vaquero, J. L. Olcoz, R. Jover, J. González-Gallego, M. V. García-Mediavilla, and S. Sánchez-Campos. 2017. 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 Radical Biology & Medicine 102:188–202. doi: 10.1016/j.freeradbiomed.2016.11.037.
   PubMed Web of Science ®Google Scholar
• Rezvan, N., A. Moini, L. Janani, K. Mohammad, A. Saedisomeolia, M. Nourbakhsh, et al. 2017. Effects of quercetin on adiponectin-mediated insulin sensitivity in polycystic ovary syndrome: A randomized placebo-controlled double-blind clinical trial. Hormone and Metabolic Research 49 (2):115–21.
   PubMed Web of Science ®Google Scholar
• Riva, A., A. Corti, G. Belcaro, M. R. Cesarone, M. Dugall, G. Vinciguerra, et al. 2018. Interaction study between antiplatelet agents, anticoagulants, diabetic therapy and a novel delivery form of quercetin. Minerva Cardioangiologica 67 (1):79–83.
   PubMed Web of Science ®Google Scholar
• Rivera, L., R. Morón, M. Sánchez, A. Zarzuelo, and M. Galisteo. 2008. Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity (Silver Spring, MD) 16 (9):2081–7. doi: 10.1038/oby.2008.315.
   PubMed Web of Science ®Google Scholar
• Roslan, J., N. Giribabu, K. Karim, and N. Salleh. 2017. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 86:570–82. doi: 10.1016/j.biopha.2016.12.044.
   PubMed Web of Science ®Google Scholar
• Sandeep, M., and C. Nandini. 2017. Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats. Biomedicine & Pharmacotherapy 94:605–11.
   PubMed Web of Science ®Google Scholar
• Scalbert, A., C. Morand, C. Manach, and C. Rémésy. 2002. Absorption and metabolism of polyphenols in the gut and impact on health. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 56 (6):276–82. doi: 10.1016/s0753-3322(02)00205-6.
   PubMed Web of Science ®Google Scholar
• Senyigit, A., S. Durmus, E. B. Mirzatas, N. P. Ozsobacı, R. Gelisgen, M. Tuncdemir, D. Ozcelik, G. Simsek, and H. Uzun. 2019. Effects of quercetin on lipid and protein damage in the liver of streptozotocin-induced experimental diabetic rats. Journal of Medicinal Food 22 (1):52–6. doi: 10.1089/jmf.2018.0030.
   PubMed Web of Science ®Google Scholar
• Sequeira, I. R., and S. D. Poppitt. 2017. Unfolding novel mechanisms of polyphenol flavonoids for better glycaemic control: Targeting pancreatic islet amyloid polypeptide (IAPP). Nutrients 9 (7):788. doi: 10.3390/nu9070788.
   PubMed Web of Science ®Google Scholar
• Shabbir, U., M. Rubab, E. B.-M. Daliri, R. Chelliah, A. Javed, and D.-H. Oh. 2021. Curcumin, quercetin, catechins and metabolic diseases: The role of gut microbiota. Nutrients 13 (1):206. doi: 10.3390/nu13010206.
   PubMed Web of Science ®Google Scholar
• Sharifi-Rad, J., C. F. Rodrigues, F. Sharopov, A. O. Docea, A. Can Karaca, M. Sharifi-Rad, et al. 2020. Diet, lifestyle and cardiovascular diseases: Linking pathophysiology to cardioprotective effects of natural bioactive compounds. International Journal of Environmental Research and Public Health 17 (7):2326. doi: 10.3390/ijerph17072326.
   PubMed Web of Science ®Google Scholar
• Sharma, G., S. Kumar, M. Sharma, N. Upadhyay, S. Kumar, Z. Ahmed, and N. Mahindroo. 2018. Anti-diabetic, anti-oxidant and anti-adipogenic potential of quercetin rich ethyl acetate fraction of Prunus persica. Pharmacognosy Journal 10 (3):463–9. doi: 10.5530/pj.2018.3.76.
   Google Scholar
• Shi, G.-J., Y. Li, Q.-H. Cao, H.-X. Wu, X.-Y. Tang, X.-H. Gao, J.-Q. Yu, Z. Chen, and Y. Yang. 2019. In vitro and in vivo evidence that quercetin protects against diabetes and its complications: A systematic review of the literature. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 109:1085–99. doi: 10.1016/j.biopha.2018.10.130.
   PubMed Web of Science ®Google Scholar
• Shi, T., X. Bian, Z. Yao, Y. Wang, W. Gao, and C. Guo. 2020. Quercetin improves gut dysbiosis in antibiotic-treated mice. Food & Function 11 (9):8003–13. doi: 10.1039/D0FO01439G.
   PubMed Web of Science ®Google Scholar
• Shi, Y., and G. Williamson. 2016. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: A randomised, double-blinded, placebo-controlled, cross-over trial. The British Journal of Nutrition 115 (5):800–6. doi: 10.1017/S0007114515005310.
   PubMed Web of Science ®Google Scholar
• Singh, A., R. C. Zapata, A. Pezeshki, M. L. Workentine, and P. K. Chelikani. 2019. Host genetics and diet composition interact to modulate gut microbiota and predisposition to metabolic syndrome in spontaneously hypertensive stroke-prone rats. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 33 (6):6748–66. doi: 10.1096/fj.201801627RRR.
   PubMed Web of Science ®Google Scholar
• Singh, J., P. Mittal, G. Vasant Bonde, G. Ajmal, and B. Mishra. 2018. Design, optimization, characterization and in-vivo evaluation of Quercetin enveloped Soluplus®/P407 micelles in diabetes treatment. Artificial Cells, Nanomedicine, and Biotechnology 46 (sup3):S546–S55. doi: 10.1080/21691401.2018.1501379.
   PubMed Web of Science ®Google Scholar
• Singh, S., V. Kushwah, A. K. Agrawal, and S. Jain. 2018. Insulin- and quercetin-loaded liquid crystalline nanoparticles: implications on oral bioavailability, antidiabetic and antioxidant efficacy. Nanomedicine (London, England) 13 (5):521–37. doi: 10.2217/nnm-2017-0278.
   PubMed Web of Science ®Google Scholar
• Smelcerovic, A., J. Lazarevic, K. Tomovic, M. Anastasijevic, M. Jukic, G. Kocic, and M. Anderluh. 2019. An overview, advantages and therapeutic potential of nonpeptide positive allosteric modulators of glucagon-like peptide-1 receptor . Chemmedchem. 14 (5):514–21. doi: 10.1002/cmdc.201800699.
   PubMed Web of Science ®Google Scholar
• Srinivasan, P., S. Vijayakumar, S. Kothandaraman, and M. Palani. 2018. Anti-diabetic activity of quercetin extracted from Phyllanthus emblica L. fruit: In silico and in vivo approaches. Journal of Pharmaceutical Analysis 8 (2):109–18. doi: 10.1016/j.jpha.2017.10.005.
   PubMed Web of Science ®Google Scholar
• Tsalamandris, S., A. S. Antonopoulos, E. Oikonomou, G.-A. Papamikroulis, G. Vogiatzi, S. Papaioannou, S. Deftereos, and D. Tousoulis. 2019. The role of inflammation in diabetes: Current concepts and future perspectives. European Cardiology 14 (1):50–9. doi: 10.15420/ecr.2018.33.1.
   PubMed Web of Science ®Google Scholar
• Vaidehi, S., G. S. Prasath, J. U. Maheswari, and N. Rajasekar. 2020. HPLC identification of Rutin (3, 3′, 4′, 5, 7-pentahydroxyflavone-3-rhamnoglucoside) from Costus pictus leaves extract and evaluation of its antioxidant activity. Asian Journal of Medical and Biological Research 6 (2):334–9. doi: 10.3329/ajmbr.v6i2.48081.
   Google Scholar
• van den Elsen, L. W., H. C. Poyntz, L. S. Weyrich, W. Young, and E. E. Forbes-Blom. 2017. Embracing the gut microbiota: The new frontier for inflammatory and infectious diseases. Clinical & Translational Immunology 6 (1):e125. doi: 10.1038/cti.2016.91.
   PubMedGoogle Scholar
• Vessal, M., M. Hemmati, and M. Vasei. 2003. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comparative biochemistry and physiology. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 135 (3):357–64. cdoi: 10.1016/S1532-0456(03)00140-6.
   PubMed Web of Science ®Google Scholar
• Wach, A., K. Pyrzyńska, and M. Biesaga. 2007. Quercetin content in some food and herbal samples. Food Chemistry 100 (2):699–704. doi: 10.1016/j.foodchem.2005.10.028.
   Web of Science ®Google Scholar
• Wang, W., C. Sun, L. Mao, P. Ma, F. Liu, J. Yang, and Y. Gao. 2016. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends in Food Science & Technology 56:21–38. doi: 10.1016/j.tifs.2016.07.004.
   Web of Science ®Google Scholar
• Williamson, G., and K. Sheedy. 2020. Effects of Polyphenols on Insulin Resistance. Nutrients 12 (10):3135. doi: 10.3390/nu12103135.
   PubMed Web of Science ®Google Scholar
• Xu, L., Y. Li, Y. Dai, and J. Peng. 2018. Natural products for the treatment of type 2 diabetes mellitus: Pharmacology and mechanisms. Pharmacological Research 130:451–65. doi: 10.1016/j.phrs.2018.01.015.
   PubMed Web of Science ®Google Scholar
• Yang, D. K., and H. S. Kang. 2018. Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomolecules & Therapeutics 26 (2):130–8. doi: 10.4062/biomolther.2017.254.
   PubMed Web of Science ®Google Scholar
• Yazıcı, S., C. U. Ozcan, A. A. Hismiogullari, F. B. Sunay, T. Ozcan, E. A. Berksoy, and E. Aksoz. 2018. Protective effects of quercetin on necrotizing enterocolitis in a neonatal rat model. American Journal of Perinatology 35 (5):434–40. doi: 10.1055/s-0037-1608660.
   PubMed Web of Science ®Google Scholar
• Ying, L., M. T. Chaudhry, F. Xiao, Y. Mao, M. Wang, B. Wang, S. Wang, and Y. Li. 2020. The effects and mechanism of quercetin dietary supplementation in streptozotocin-induced hyperglycemic arbor acre broilers. Oxidative Medicine and Cellular Longevity 2020:9585047. doi: 10.1155/2020/9585047.
   PubMed Web of Science ®Google Scholar
• Zahedi, M., R. Ghiasvand, A. Feizi, G. Asgari, and L. Darvish. 2013. Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes: A double-blind randomized controlled clinical trial. International Journal of Preventive Medicine 4 (7):777.
   PubMedGoogle Scholar
• Zhang, Y., H. Dong, M. Wang, and J. Zhang. 2016. Quercetin isolated from Toona sinensis leaves attenuates hyperglycemia and protects hepatocytes in high-carbohydrate/high-fat diet and alloxan induced experimental diabetic mice. Journal of Diabetes Research 2016:8492780. doi: 10.1155/2016/8492780.
   PubMed Web of Science ®Google Scholar
• Zhao, L., Q. Zhang, W. Ma, F. Tian, H. Shen, and M. Zhou. 2017. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food & Function 8 (12):4644–56. doi: 10.1039/C7FO01383C.
   PubMed Web of Science ®Google Scholar
• Zhu, X., Z. Qiu, W. Ouyang, J. Miao, P. Xiong, D. Mao, K. Feng, M. Li, M. Luo, H. Xiao, et al. 2019. Hepatic transcriptome and proteome analyses provide new insights into the regulator mechanism of dietary avicularin in diabetic mice. Food Research International (Ottawa, ON) 125:108570. doi: 10.1016/j.foodres.2019.108570.
   PubMed Web of Science ®Google Scholar
• Zhuang, M., H. Qiu, P. Li, L. Hu, Y. Wang, and L. Rao. 2018. Islet protection and amelioration of type 2 diabetes mellitus by treatment with quercetin from the flowers of Edgeworthia gardneri. Drug Design, Development and Therapy 12:955–66. doi: 10.2147/DDDT.S153898.
   PubMed Web of Science ®Google Scholar