Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Review Article

Flavonoids in the Treatment of Diabetes: Clinical Outcomes and Mechanism to Ameliorate Blood Glucose Levels

Author(s): Dunya Al Duhaidahawi*, Samer A. Hasan and Haider F.S. Al Zubaidy

Volume 17, Issue 6, 2021

Published on: 07 December, 2020

Article ID: e120720188794 Pages: 17

DOI: 10.2174/1573399817666201207200346

Price: $65

Abstract

Background: For thousands of years, natural food products have been used as a medicine for treating diseases that affect the human body, including diabetes mellitus (DM). Lately, several investigations have been performed on the flavonoid derivatives of plant origin, and their biological activity has been extensively studied.

Methods: Given our need to know more mechanisms for treating DM, we performed a thorough research review on treating diabetes mellitus based on flavonoids, their therapeutic potential, and biological action.

Results: Flavonoids reduce complications in addition to their vital role as effective supplements for preventing diabetes mellitus by regulating glucose metabolism, lipid profile, liver enzyme activity, a protein kinase inhibitor, PPAR, and AMPK with NF-κB.

Conclusion: The articles that we reviewed showed the positive role of flavonoids, which in a certain way reduce diabetes, but their side effects still need to be studied further.This review is focused on describing the different types of dietary flavonoids along with their mechanisms of reducing blood glucose and enhancing insulin sensitivity, as well as their side effects.

Keywords: Diabetes mellitus, iresistance, flavonoids, lipogenesis, kaempferol, hesperidin.

[1]
Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus-present and future perspectives. Nat Rev Endocrinol 2011; 8(4): 228-36.
[http://dx.doi.org/10.1038/nrendo.2011.183] [PMID: 22064493]
[2]
Babu PV, Liu D, Gilbert ER. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 2013; 24(11): 1777-89.
[http://dx.doi.org/10.1016/j.jnutbio.2013.06.003] [PMID: 24029069]
[3]
Tian-yang W, Li Q, Bi K. Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian. J Pharm Sci 2018; 13: 12-23.
[4]
Graf BA, Milbury PE, Blumberg JB. Flavonols, flavones, flavanones, and human health: epidemiological evidence. J Med Food 2005; 8(3): 281-90.
[http://dx.doi.org/10.1089/jmf.2005.8.281] [PMID: 16176136]
[5]
Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 2008; 88(11): 1322-35.
[http://dx.doi.org/10.2522/ptj.20080008] [PMID: 18801863]
[6]
Halpern A, Mancini MC, Magalhães ME, et al. Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: from diagnosis to treatment. Diabetol Metab Syndr 2010; 2(1): 55.
[http://dx.doi.org/10.1186/1758-5996-2-55] [PMID: 20718958]
[7]
Boateng GO, Adams EA, Odei Boateng M, Luginaah IN, Taabazuing M-M. Obesity and the burden of health risks among the elderly in Ghana: A population study. PLoS One 2017; 12(11): e0186947.
[http://dx.doi.org/10.1371/journal.pone.0186947] [PMID: 29117264]
[8]
Chaudhury A, Duvoor C, Reddy Dendi VS, et al. Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol (Lausanne) 2017; 8: 6.
[http://dx.doi.org/10.3389/fendo.2017.00006] [PMID: 28167928]
[9]
Maas J. New approaches in research and development of anti-diabetic drugs: an industry perspective. Ther Adv Endocrinol Metab 2012; 3(4): 109-12.
[http://dx.doi.org/10.1177/2042018812457406] [PMID: 23185684]
[10]
Levien TL, Baker DE. New Drugs in Development for the Treatment of Diabetes. Diabetes Spectr 2009; 22(2): 92-106.
[http://dx.doi.org/10.2337/diaspect.22.2.92]
[11]
Covington P, Christopher R, Davenport M, et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: a randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther 2008; 30(3): 499-512.
[http://dx.doi.org/10.1016/j.clinthera.2008.03.004] [PMID: 18405788]
[12]
Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol 2019; 11(3): 45-63.
[PMID: 31333808]
[13]
Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 2014; 6(1): a009191.
[http://dx.doi.org/10.1101/cshperspect.a009191] [PMID: 24384568]
[14]
Copps KD, White MF. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia 2012; 55(10): 2565-82.
[http://dx.doi.org/10.1007/s00125-012-2644-8] [PMID: 22869320]
[15]
Cipok M, Aga-Mizrachi S, Bak A, et al. Protein kinase Calpha regulates insulin receptor signaling in skeletal muscle. Biochem Biophys Res Commun 2006; 345(2): 817-24.
[http://dx.doi.org/10.1016/j.bbrc.2006.05.008] [PMID: 16707110]
[16]
Ueki K, Kondo T, Kahn CR. Suppressor of Cytokine Signaling 1 (SOCS-1) and SOCS-3 Cause Insulin Resistance through Inhibition of Tyrosine Phosphorylation of Insulin Receptor Substrate Proteins by Discrete Mechanisms. Mol Cell Biol 2005; 25(19): 8762.
[http://dx.doi.org/10.1128/MCB.25.19.8762.2005] [PMID: 15169905]
[17]
Galic S, Hauser C, Kahn BB, et al. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol Cell Biol 2005; 25(2): 819-29.
[http://dx.doi.org/10.1128/MCB.25.2.819-829.2005] [PMID: 15632081]
[18]
Wada T, Sasaoka T, Funaki M, et al. Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5′-phosphatase catalytic activity. Mol Cell Biol 2001; 21(5): 1633-46.
[http://dx.doi.org/10.1128/MCB.21.5.1633-1646.2001] [PMID: 11238900]
[19]
Liu P, Li G, Wu J, et al. Vaspin promotes 3T3-L1 preadipocyte differentiation. Exp Biol Med (Maywood) 2015; 240(11): 1520-7.
[http://dx.doi.org/10.1177/1535370214565081] [PMID: 25585626]
[20]
Jacobi D, Stanya KJ, Lee CH. Adipose tissue signaling by nuclear receptors in metabolic complications of obesity. Adipocyte 2012; 1(1): 4-12.
[http://dx.doi.org/10.4161/adip.19036] [PMID: 22916336]
[21]
Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006; 444(7121): 847-53.
[http://dx.doi.org/10.1038/nature05483] [PMID: 17167472]
[22]
Jin D, Sun J, Huang J, et al. TNF-α reduces g0s2 expression and stimulates lipolysis through PPAR-γ inhibition in 3T3-L1 adipocytes. Cytokine 2014; 69(2): 196-205.
[http://dx.doi.org/10.1016/j.cyto.2014.06.005] [PMID: 24993166]
[23]
Sears B, Perry M. The role of fatty acids in insulin resistance. Lipids Health Dis 2015; 14(1): 121.
[http://dx.doi.org/10.1186/s12944-015-0123-1] [PMID: 26415887]
[24]
Ye J. Mechanisms of insulin resistance in obesity. Front Med 2013; 7(1): 14-24.
[http://dx.doi.org/10.1007/s11684-013-0262-6] [PMID: 23471659]
[25]
Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, Del Cañizo-Gómez FJ. Update on the treatment of type 2 diabetes mellitus. World J Diabetes 2016; 7(17): 354-95.
[http://dx.doi.org/10.4239/wjd.v7.i17.354] [PMID: 27660695]
[26]
Rines AK, Sharabi K, Tavares CD, Puigserver P. Targeting hepatic glucose metabolism in the treatment of type 2 diabetes. Nat Rev Drug Discov 2016; 15(11): 786-804.
[http://dx.doi.org/10.1038/nrd.2016.151] [PMID: 27516169]
[27]
Horodyska K, Luszczynska A, van den Berg M, et al. Good practice characteristics of diet and physical activity interventions and policies: an umbrella review. BMC Public Health 2015; 15(1): 19.
[http://dx.doi.org/10.1186/s12889-015-1354-9] [PMID: 25604454]
[28]
American Diabetes Association. Diagnosis and classification of diabetes mellitus Diabetes Care 2009; 32(Supplement_1): 562-7.
[29]
Wolfe BM, Kvach E, Eckel RH. Treatment of Obesity: Weight Loss and Bariatric Surgery. Circ Res 2016; 118(11): 1844-55.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.307591] [PMID: 27230645]
[30]
Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab 2016; 20(4): 546-51.
[http://dx.doi.org/10.4103/2230-8210.183480] [PMID: 27366724]
[31]
Herman MA, Kahn BB. Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony. J Clin Invest 2006; 116(7): 1767-75.
[http://dx.doi.org/10.1172/JCI29027] [PMID: 16823474]
[32]
Olson AL. Regulation of GLUT4 and Insulin-Dependent Glucose Flux. ISRN Mol Biol 2012; 856987.
[http://dx.doi.org/10.5402/2012/856987] [PMID: 27335671]
[33]
Zhang Z, Liew CW, Handy DE, et al. High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosis. FASEB J 2010; 24(5): 1497-505.
[http://dx.doi.org/10.1096/fj.09-136572] [PMID: 20032314]
[34]
Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nat Med 2017; 23(7): 804-14.
[http://dx.doi.org/10.1038/nm.4350] [PMID: 28697184]
[35]
Erion DM, Park HJ, Lee HY. The role of lipids in the pathogenesis and treatment of type 2 diabetes and associated co-morbidities. BMB Rep 2016; 49(3): 139-48.
[http://dx.doi.org/10.5483/BMBRep.2016.49.3.268] [PMID: 26728273]
[36]
Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci 2016; 5: e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[37]
Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J 2013; 162750.
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[38]
Wang T-Y, Li Q, Bi KS. Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. Asian J Pharm Sci 2018; 13(1): 12-23.
[http://dx.doi.org/10.1016/j.ajps.2017.08.004] [PMID: 32104374]
[39]
Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A. Flavonoids and Other Phenolic Compounds from Medicinal Plants for Pharmaceutical and Medical Aspects: An Overview. Medicines (Basel) 2018; 5(3): 93.
[http://dx.doi.org/10.3390/medicines5030093] [PMID: 30149600]
[40]
Giannini I, Amato A, Basso L, et al. Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol 2015; 19(6): 339-45.
[http://dx.doi.org/10.1007/s10151-015-1302-9] [PMID: 25893991]
[41]
Francini-Pesenti F, Spinella P, Calò LA. Potential role of phytochemicals in metabolic syndrome prevention and therapy. Diabetes Metab Syndr Obes 2019; 12: 1987-2002.
[http://dx.doi.org/10.2147/DMSO.S214550] [PMID: 31632110]
[42]
Jasso-Miranda C, Herrera-Camacho I, Flores-Mendoza LK, et al. Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies. Infect Drug Resist 2019; 12: 1833-52.
[http://dx.doi.org/10.2147/IDR.S210890] [PMID: 31303775]
[43]
Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J 2016; 15(1): 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5] [PMID: 27456681]
[44]
Lankatillake C, Huynh T, Dias DA. Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants. Plant Methods 2019; 15(1): 105.
[http://dx.doi.org/10.1186/s13007-019-0487-8] [PMID: 31516543]
[45]
Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Exp Mol Med 2016; 48(3): e219.
[http://dx.doi.org/10.1038/emm.2016.6] [PMID: 26964835]
[46]
Wedick NM, Pan A, Cassidy A, et al. Dietary flavonoid intakes and risk of type 2 diabetes in US men and women. Am J Clin Nutr 2012; 95(4): 925-33.
[http://dx.doi.org/10.3945/ajcn.111.028894] [PMID: 22357723]
[47]
Cos P, Calomme M, Pieters L, Vlietinck AJ, Berghe DV. Structure-Activity Relationship of Flavonoids as Antioxidant and pro-Oxidant Compounds.Bioactive Natural Products (Part C). Elsevier 2000; pp. 307-41.
[http://dx.doi.org/10.1016/S1572-5995(00)80029-0]
[48]
Monagas M, Urpi-Sarda M, Sánchez-Patán F, et al. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct 2010; 1(3): 233-53.
[http://dx.doi.org/10.1039/c0fo00132e] [PMID: 21776473]
[49]
Liu Z, Hu M. Natural polyphenol disposition via coupled metabolic pathways. Expert Opin Drug Metab Toxicol 2007; 3(3): 389-406.
[http://dx.doi.org/10.1517/17425255.3.3.389] [PMID: 17539746]
[50]
Kawabata K, Yoshioka Y, Terao J. Role of Intestinal Microbiota in the Bioavailability and Physiological Functions of Dietary Polyphenols. Molecules 2019; 24(2): 370.
[http://dx.doi.org/10.3390/molecules24020370] [PMID: 30669635]
[51]
Klaassen CD, Cui JY. Review: Mechanisms of How the Intestinal Microbiota Alters the Effects of Drugs and Bile Acids. Drug Metab Dispos 2015; 43(10): 1505-21.
[http://dx.doi.org/10.1124/dmd.115.065698] [PMID: 26261286]
[52]
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009; 2(5): 270-8.
[http://dx.doi.org/10.4161/oxim.2.5.9498] [PMID: 20716914]
[53]
Gee JM, DuPont MS, Rhodes MJC, Johnson IT. Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radic Biol Med 1998; 25(1): 19-25.
[http://dx.doi.org/10.1016/S0891-5849(98)00020-3] [PMID: 9655517]
[54]
Letan A. Secondary (Metal-Complexing) Activity. The relation of structure to antioxidant activity of quercetin and some of its derivatives. J Food Sci 1966; 31(3): 395-9.
[http://dx.doi.org/10.1111/j.1365-2621.1966.tb00512.x]
[55]
Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004; 79(5): 727-47.
[http://dx.doi.org/10.1093/ajcn/79.5.727] [PMID: 15113710]
[56]
Yao Z, Gu Y, Zhang Q, et al. Estimated daily quercetin intake and association with the prevalence of type 2 diabetes mellitus in Chinese adults. Eur J Nutr 2019; 58(2): 819-30.
[http://dx.doi.org/10.1007/s00394-018-1713-2] [PMID: 29754250]
[57]
Bule M, Abdurahman A, Nikfar S, Abdollahi M, Amini M. Antidiabetic effect of quercetin: A systematic review and meta-analysis of animal studies. Food Chem Toxicol 2019; 125: 494-502.
[http://dx.doi.org/10.1016/j.fct.2019.01.037] [PMID: 30735748]
[58]
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017; 60(9): 1577-85.
[http://dx.doi.org/10.1007/s00125-017-4342-z] [PMID: 28776086]
[59]
Braccini L, Ciraolo E, Campa CC, et al. PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling. Nat Commun 2015; 6(1): 7400.
[http://dx.doi.org/10.1038/ncomms8400] [PMID: 26100075]
[60]
Sirovina D, Orsolić N, Koncić MZ, Kovacević G, Benković V, Gregorović G. Quercetin vs chrysin: effect on liver histopathology in diabetic mice. Hum Exp Toxicol 2013; 32(10): 1058-66.
[http://dx.doi.org/10.1177/0960327112472993] [PMID: 23357962]
[61]
Saravanan G, Ponmurugan P. S-allylcysteine Improves Streptozotocin-Induced Alterations of Blood Glucose, Liver Cytochrome P450 2E1, Plasma Antioxidant System, and Adipocytes Hormones in Diabetic Rats. Int J Endocrinol Metab 2013; 11(4): e10927.
[http://dx.doi.org/10.5812/ijem.10927] [PMID: 24719626]
[62]
Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol 2003; 135C(3): 357-64.
[http://dx.doi.org/10.1016/S1532-0456(03)00140-6] [PMID: 12927910]
[63]
Eid HM, Nachar A, Thong F, Sweeney G, Haddad PS. The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes. Pharmacogn Mag 2015; 11(41): 74-81.
[http://dx.doi.org/10.4103/0973-1296.149708] [PMID: 25709214]
[64]
Kobori M, Masumoto S, Akimoto Y, Takahashi Y. Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice. Mol Nutr Food Res 2009; 53(7): 859-68.
[http://dx.doi.org/10.1002/mnfr.200800310] [PMID: 19496084]
[65]
Eitah HE, Maklad YA, Abdelkader NF, Gamal El Din AA, Badawi MA, Kenawy SA. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicol Appl Pharmacol 2019; 365: 30-40.
[http://dx.doi.org/10.1016/j.taap.2018.12.011] [PMID: 30576699]
[66]
Dai X, Ding Y, Zhang Z, Cai X, Li Y. Quercetin and quercitrin protect against cytokine-induced injuries in RINm5F β-cells via the mitochondrial pathway and NF-κB signaling. Int J Mol Med 2013; 31(1): 265-71.
[http://dx.doi.org/10.3892/ijmm.2012.1177] [PMID: 23138875]
[67]
Kreft S, Knapp M, Kreft I. Extraction of rutin from buckwheat (Fagopyrum esculentumMoench) seeds and determination by capillary electrophoresis. J Agric Food Chem 1999; 47(11): 4649-52.
[http://dx.doi.org/10.1021/jf990186p] [PMID: 10552865]
[68]
Enogieru AB, Haylett W, Hiss DC, Bardien S, Ekpo OE. Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders. Oxid Med Cell Longev 2018; 2018: e6241017.
[http://dx.doi.org/10.1155/2018/6241017] [PMID: 30050657]
[69]
Niture NT, Ansari AA, Naik SR. Anti-hyperglycemic activity of rutin in streptozotocin-induced diabetic rats: an effect mediated through cytokines, antioxidants and lipid biomarkers. Indian J Exp Biol 2014; 52(7): 720-7.
[PMID: 25059040]
[70]
Ghorbani A. Mechanisms of antidiabetic effects of flavonoid rutin. Biomed Pharmacother 2017; 96: 305-12.
[http://dx.doi.org/10.1016/j.biopha.2017.10.001] [PMID: 29017142]
[71]
Stanley Mainzen Prince P, Kamalakkannan N. Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes. J Biochem Mol Toxicol 2006; 20(2): 96-102.
[http://dx.doi.org/10.1002/jbt.20117] [PMID: 16615078]
[72]
Hao HH, Shao ZM, Tang DQ, et al. Preventive effects of rutin on the development of experimental diabetic nephropathy in rats. Life Sci 2012; 91(19-20): 959-67.
[http://dx.doi.org/10.1016/j.lfs.2012.09.003] [PMID: 23000098]
[73]
Ola MS, Ahmed MM, Ahmad R, Abuohashish HM, Al-Rejaie SS, Alhomida AS. Neuroprotective Effects of Rutin in Streptozotocin-Induced Diabetic Rat Retina. J Mol Neurosci 2015; 56(2): 440-8.
[http://dx.doi.org/10.1007/s12031-015-0561-2] [PMID: 25929832]
[74]
Calderón-Montaño JM, Burgos-Morón E, Pérez-Guerrero C, López-Lázaro M. A review on the dietary flavonoid kaempferol. Mini Rev Med Chem 2011; 11(4): 298-344.
[http://dx.doi.org/10.2174/138955711795305335] [PMID: 21428901]
[75]
Chen AY, Chen YC. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem 2013; 138(4): 2099-107.
[http://dx.doi.org/10.1016/j.foodchem.2012.11.139] [PMID: 23497863]
[76]
An G, Gallegos J, Morris ME. The bioflavonoid kaempferol is an Abcg2 substrate and inhibits Abcg2-mediated quercetin efflux. Drug Metab Dispos 2011; 39(3): 426-32.
[http://dx.doi.org/10.1124/dmd.110.035212] [PMID: 21139040]
[77]
Ikechukwu OJ, Ifeanyi OS. The Antidiabetic Effects of The Bioactive Flavonoid (Kaempferol-3-O-β-D-6P- Coumaroyl Glucopyranoside) Isolated From Allium cepa. Recent Pat Antiinfect Drug Discov 2016; 11(1): 44-52.
[http://dx.doi.org/10.2174/1574891X11666151105130233] [PMID: 26536892]
[78]
Ježek P, Jabůrek M, Plecitá-Hlavatá L. Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic β-Cells to Type 2 Diabetes. Antioxid Redox Signal 2019; 31(10): 722-51.
[http://dx.doi.org/10.1089/ars.2018.7656] [PMID: 30450940]
[79]
Zanatta L, Rosso A, Folador P, et al. Insulinomimetic effect of kaempferol 3-neohesperidoside on the rat soleus muscle. J Nat Prod 2008; 71(4): 532-5.
[http://dx.doi.org/10.1021/np070358+] [PMID: 18303854]
[80]
Kang HW, Lee SG, Otieno D, Ha K. Flavonoids, Potential Bioactive Compounds, and Non-Shivering Thermogenesis. Nutrients 2018; 10(9): 1168.
[http://dx.doi.org/10.3390/nu10091168] [PMID: 30149637]
[81]
Alkhalidy H, Moore W, Wang Y, et al. The Flavonoid Kaempferol Ameliorates Streptozotocin-Induced Diabetes by Suppressing Hepatic Glucose Production. Molecules 2018; 23(9): 2338.
[http://dx.doi.org/10.3390/molecules23092338] [PMID: 30216981]
[82]
Sharma D, Gondaliya P, Tiwari V, Kalia K. Kaempferol attenuates diabetic nephropathy by inhibiting RhoA/Rho-kinase mediated inflammatory signalling. Biomed Pharmacother 2019; 109: 1610-9.
[http://dx.doi.org/10.1016/j.biopha.2018.10.195] [PMID: 30551415]
[83]
Lu CL, Li XF. A Review of Oenanthe javanica (Blume) DC. as Traditional Medicinal Plant and Its Therapeutic Potential. Evid Based Complement Alternat Med 2019; 6495819.
[http://dx.doi.org/10.1155/2019/6495819] [PMID: 31057651]
[84]
Gong G, Guan Y-Y, Zhang Z-L, et al. Isorhamnetin: A review of pharmacological effects. Biomed Pharmacother 2020; 128: 110301.
[http://dx.doi.org/10.1016/j.biopha.2020.110301] [PMID: 32502837]
[85]
Lee YS, Lee S, Lee HS, Kim BK, Ohuchi K, Shin KH. Inhibitory effects of isorhamnetin-3-O-beta-D-glucoside from Salicornia herbacea on rat lens aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. Biol Pharm Bull 2005; 28(5): 916-8.
[http://dx.doi.org/10.1248/bpb.28.916] [PMID: 15863906]
[86]
Rodríguez-Rodríguez C, Torres N, Gutiérrez-Uribe JA, et al. The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a mouse model of diet induced obesity. Food Funct 2015; 6(3): 805-15.
[http://dx.doi.org/10.1039/C4FO01092B] [PMID: 25588195]
[87]
Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal 2013; 19(2): 151-62.
[http://dx.doi.org/10.1089/ars.2012.4901] [PMID: 23121441]
[88]
Constantin RP, Constantin J, Pagadigorria CL, et al. The actions of fisetin on glucose metabolism in the rat liver. Cell Biochem Funct 2010; 28(2): 149-58.
[http://dx.doi.org/10.1002/cbf.1635] [PMID: 20084677]
[89]
Prasath GS, Sundaram CS, Subramanian SP. Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats. Endocrine 2013; 44(2): 359-68.
[http://dx.doi.org/10.1007/s12020-012-9866-x] [PMID: 23277230]
[90]
Kim HJ, Kim SH, Yun JM. Fisetin inhibits hyperglycemia-induced proinflammatory cytokine production by epigenetic mechanisms. eCAM 2012; 2012: 639469.
[91]
Prasath GS, Subramanian SP. Modulatory effects of fisetin, a bioflavonoid, on hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in hepatic and renal tissues in streptozotocin-induced diabetic rats. Eur J Pharmacol 2011; 668(3): 492-6.
[http://dx.doi.org/10.1016/j.ejphar.2011.07.021] [PMID: 21816145]
[92]
Althunibat OY, Al Hroob AM, Abukhalil MH, Germoush MO, Bin-Jumah M, Mahmoud AM. Fisetin ameliorates oxidative stress, inflammation and apoptosis in diabetic cardiomyopathy. Life Sci 2019; 221: 83-92.
[http://dx.doi.org/10.1016/j.lfs.2019.02.017] [PMID: 30742869]
[93]
Kim HJ, Kim SH, Yun J-M. Fisetin inhibits hyperglycemia-induced proinflammatory cytokine production by epigenetic mechanisms. Evid Based Complement Alternat Med 2012; 2012: e639469.
[http://dx.doi.org/10.1155/2012/639469] [PMID: 23320034]
[94]
Sandireddy R, Yerra VG, Komirishetti P, Areti A, Kumar A. Fisetin Imparts Neuroprotection in Experimental Diabetic Neuropathy by Modulating Nrf2 and NF-κB Pathways. Cell Mol Neurobiol 2016; 36(6): 883-92.
[http://dx.doi.org/10.1007/s10571-015-0272-9] [PMID: 26399251]
[95]
Jin H, Lee WS, Eun SY, et al. Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB-231 partly through suppression of the Akt pathway. Int J Oncol 2014; 45(4): 1629-37.
[http://dx.doi.org/10.3892/ijo.2014.2535] [PMID: 24993541]
[96]
Lee GJ, Cho IA, Oh JS, et al. Anticatabolic Effects of Morin through the Counteraction of Interleukin-1β-Induced Inflammation in Rat Primary Chondrocytes. Cells Tissues Organs 2019; 207(1): 21-33.
[http://dx.doi.org/10.1159/000500323] [PMID: 31256148]
[97]
Vishnukumar S, Stephan R. Effect of morin on lipidperoxides and antioxidants in streptozotocin-induced diabetic rats. Int J Pharma Bio Sci 2012; 3(4): 770-80.
[98]
Kitagawa S, Sakamoto H, Tano H. Inhibitory effects of flavonoids on free radical-induced hemolysis and their oxidative effects on hemoglobin. Chem Pharm Bull (Tokyo) 2004; 52(8): 999-1001.
[http://dx.doi.org/10.1248/cpb.52.999] [PMID: 15305001]
[99]
Vanitha P, Uma C, Suganya N, et al. Modulatory effects of morin on hyperglycemia by attenuating the hepatic key enzymes of carbohydrate metabolism and β-cell function in streptozotocin-induced diabetic rats. Environ Toxicol Pharmacol 2014; 37(1): 326-35.
[http://dx.doi.org/10.1016/j.etap.2013.11.017] [PMID: 24384280]
[100]
Unuofin JO, Lebelo SL. Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review. Oxid Med Cell Longev 2020; 2020: 1356893.
[http://dx.doi.org/10.1155/2020/1356893] [PMID: 32148647]
[101]
Fukui K, Matsumoto T, Nakamura S, Nakayama M, Horie T. Synthetic studies of the flavone derivatives: VII. The synthesis of jaceidin. Bull Chem Soc Jpn 1968; 41(6): 1413-7.
[http://dx.doi.org/10.1246/bcsj.41.1413]
[102]
Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res 2015; 29(3): 323-31.
[http://dx.doi.org/10.1002/ptr.5256] [PMID: 25394264]
[103]
Aboismaiel MG, El-Mesery M, El-Karef A, El-Shishtawy MM. Hesperetin upregulates Fas/FasL expression and potentiates the antitumor effect of 5-fluorouracil in rat model of hepatocellular carcinoma. Egypt J Basic Appl Sci 2020; 7(1): 20-34.
[http://dx.doi.org/10.1080/2314808X.2019.1707627]
[104]
Jung UJ, Lee MK, Jeong KS, Choi MS. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. J Nutr 2004; 134(10): 2499-503.
[http://dx.doi.org/10.1093/jn/134.10.2499] [PMID: 15465737]
[105]
Zeka K, Ruparelia K, Arroo RRJ, Budriesi R, Micucci M. Flavonoids and Their Metabolites: Prevention in Cardiovascular Diseases and Diabetes. Diseases 2017; 5(3): 19.
[http://dx.doi.org/10.3390/diseases5030019] [PMID: 32962323]
[106]
Agrawal YO, Sharma PK, Shrivastava B, et al. Hesperidin produces cardioprotective activity via PPAR-γ pathway in ischemic heart disease model in diabetic rats. PLoS One 2014; 9(11): e111212.
[http://dx.doi.org/10.1371/journal.pone.0111212] [PMID: 25369053]
[107]
Akiyama S, Katsumata S, Suzuki K, Ishimi Y, Wu J, Uehara M. Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. J Clin Biochem Nutr 2010; 46(1): 87-92.
[http://dx.doi.org/10.3164/jcbn.09-82] [PMID: 20104270]
[108]
Dokumacioglu E, Iskender H, Musmul A. Effect of hesperidin treatment on α-Klotho/FGF-23 pathway in rats with experimentally-induced diabetes. Biomed Pharmacother 2019; 109: 1206-10.
[http://dx.doi.org/10.1016/j.biopha.2018.10.192] [PMID: 30551370]
[109]
Ashafaq M, Varshney L, Khan MH, et al. Neuromodulatory effects of hesperidin in mitigating oxidative stress in streptozotocin induced diabetes. BioMed Res Int 2014; 2014: e249031.
[http://dx.doi.org/10.1155/2014/249031] [PMID: 25050332]
[110]
Panda S, Kar A. Apigenin (4‘,5,7-trihydroxyflavone) regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice. J Pharm Pharmacol 2007; 59(11): 1543-8.
[http://dx.doi.org/10.1211/jpp.59.11.0012] [PMID: 17976266]
[111]
Rauter A P, Martins A, Borges C, et al. Antihyperglycaemic and protective effects of flavonoids on streptozotocin-induced diabetic rats Phytother Res 2010; 24(Suppl.2): S133-8.
[http://dx.doi.org/10.1002/ptr.3017]
[112]
Richard AJ, Amini-Vaughan Z, Ribnicky DM, Stephens JM. Naringenin inhibits adipogenesis and reduces insulin sensitivity and adiponectin expression in adipocytes. Evid Based Complement Alternat Med 2013; 549750.
[http://dx.doi.org/10.1155/2013/549750] [PMID: 23983791]
[113]
Jasmin , Jaitak V. A Review on Molecular Mechanism of Flavonoids as Antidiabetic Agents. Mini Rev Med Chem 2019; 19(9): 762-86.
[http://dx.doi.org/10.2174/1389557519666181227153428] [PMID: 30588881]
[114]
Pinent M, Castell A, Baiges I, Montagut G, Arola L, Ardévol A. Bioactivity of Flavonoids on Insulin-Secreting Cells. Compr Rev Food Sci Food Saf 2008; 7(4): 299-308.
[http://dx.doi.org/10.1111/j.1541-4337.2008.00048.x]
[115]
Hameed A, Hafizur RM, Hussain N, et al. Eriodictyol stimulates insulin secretion through cAMP/PKA signaling pathway in mice islets. Eur J Pharmacol 2018; 820: 245-55.
[http://dx.doi.org/10.1016/j.ejphar.2017.12.015] [PMID: 29229531]
[116]
Lee SE, Yang H, Son GW, et al. Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression. Int J Mol Sci 2015; 16(7): 14526-39.
[http://dx.doi.org/10.3390/ijms160714526] [PMID: 26132561]
[117]
Guo J, Li C, Yang C, et al. Liraglutide reduces hepatic glucolipotoxicity-induced liver cell apoptosis through NRF2 signaling in Zucker diabetic fatty rats. Mol Med Rep 2018; 17(6): 8316-24.
[http://dx.doi.org/10.3892/mmr.2018.8919] [PMID: 29693190]
[118]
Zeghad N, Ahmed E, Belkhiri A, Heyden YV, Demeyer K. Antioxidant activity of Vitis vinifera, Punica granatum, Citrus aurantium and Opuntia ficus indica fruits cultivated in Algeria. Heliyon 2019; 5(4): e01575.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01575] [PMID: 31183435]
[119]
Kao YC, Zhou C, Sherman M, Laughton CA, Chen S. Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study. Environ Health Perspect 1998; 106(2): 85-92.
[http://dx.doi.org/10.1289/ehp.9810685] [PMID: 9435150]
[120]
Jung UJ, Cho Y-Y, Choi M-S. Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice. Nutrients 2016; 8(5): 305.
[http://dx.doi.org/10.3390/nu8050305] [PMID: 27213439]
[121]
Zang M, Xu S, Maitland-Toolan KA, et al. Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis Diabetic LDL Receptor–Deficient Mice diabetes 2006; 55(8): 2180-91.
[122]
Wang N, Yi WJ, Tan L, et al. Apigenin attenuates streptozotocin-induced pancreatic β cell damage by its protective effects on cellular antioxidant defense. In Vitro Cell Dev Biol Anim 2017; 53(6): 554-63.
[http://dx.doi.org/10.1007/s11626-017-0135-4] [PMID: 28181104]
[123]
Malik S, Suchal K, Khan SI, et al. Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways. Am J Physiol Renal Physiol 2017; 313(2): F414-22.
[http://dx.doi.org/10.1152/ajprenal.00393.2016] [PMID: 28566504]
[124]
Miean KH, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem 2001; 49(6): 3106-12.
[http://dx.doi.org/10.1021/jf000892m] [PMID: 11410016]
[125]
Ding L, Jin D, Chen X. Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes. J Nutr Biochem 2010; 21(10): 941-7.
[http://dx.doi.org/10.1016/j.jnutbio.2009.07.009] [PMID: 19954946]
[126]
Jia L, Xing J, Ding Y, et al. Hyperuricemia causes pancreatic β- cell death and dysfunction through NF-κB signaling pathway. PLoS One 2013; 8(10): e78284.
[http://dx.doi.org/10.1371/journal.pone.0078284] [PMID: 24205181]
[127]
Zang Y, Igarashi K, Li Y. Anti-diabetic effects of luteolin and luteolin-7-O-glucoside on KK-A(y) mice. Biosci Biotechnol Biochem 2016; 80(8): 1580-6.
[http://dx.doi.org/10.1080/09168451.2015.1116928] [PMID: 27170065]
[128]
Kim MS, Hur HJ, Kwon DY, Hwang JT. Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice. Mol Cell Endocrinol 2012; 358(1): 127-34.
[http://dx.doi.org/10.1016/j.mce.2012.03.013] [PMID: 22476082]
[129]
Ramalingam S, Ramasamy S M, Vasu G. Antihyperglycemic Potential of Back Tea Extract Attenuates Tricarboxylic Acid Cycle Enzymes by Modulating Carbohydrate Metabolic Enzymes in Streptozotocin-Induced Diabetic Rats Ind J Clin Biochem 2019; 35(3): 322-30.
[130]
Liu Y, Han J, Zhou Z, Li D. Tangeretin inhibits streptozotocin-induced cell apoptosis via regulating NF-κB pathway in INS-1 cells. J Cell Biochem 2019; 120(3): 3286-93.
[http://dx.doi.org/10.1002/jcb.27596] [PMID: 30216514]
[131]
Thilakarathna SH, Rupasinghe HP. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients 2013; 5(9): 3367-87.
[http://dx.doi.org/10.3390/nu5093367] [PMID: 23989753]
[132]
Samarghandian S, Azimi-Nezhad M, Samini F, Farkhondeh T. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 2016; 94(4): 388-93.
[http://dx.doi.org/10.1139/cjpp-2014-0412] [PMID: 26863330]
[133]
Satyanarayana K, Sravanthi K, Shaker IA, Ponnulakshmi R, Selvaraj J. Role of chrysin on expression of insulin signaling molecules. J Ayurveda Integr Med 2015; 6(4): 248-58.
[http://dx.doi.org/10.4103/0975-9476.157951] [PMID: 26834424]
[134]
Kuroyanagi M, Ishii H, Kawahara N, et al. Flavonoid glycosides and limonoids from Citrus molasses. J Nat Med 2008; 62(1): 107-11.
[http://dx.doi.org/10.1007/s11418-007-0198-8] [PMID: 18404354]
[135]
Pari L, Srinivasan S. Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Biomed Pharmacother 2010; 64(7): 477-81.
[http://dx.doi.org/10.1016/j.biopha.2010.02.001] [PMID: 20362409]
[136]
Dinda B, Dinda M, Roy A, Dinda S. Dietary plant flavonoids in prevention of obesity and diabetes. Adv Protein Chem Struct Biol 2020; 120: 159-235.
[http://dx.doi.org/10.1016/bs.apcsb.2019.08.006] [PMID: 32085882]
[137]
Srinivasan S, Pari L. Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Chem Biol Interact 2012; 195(1): 43-51.
[http://dx.doi.org/10.1016/j.cbi.2011.10.003] [PMID: 22056647]
[138]
Kim DH, Hossain MA, Kang YJ, et al. Baicalein, an active component of Scutellaria baicalensis Georgi, induces apoptosis in human colon cancer cells and prevents AOM/DSS-induced colon cancer in mice. Int J Oncol 2013; 43(5): 1652-8.
[http://dx.doi.org/10.3892/ijo.2013.2086] [PMID: 24008356]
[139]
Stavniichuk R, Drel VR, Shevalye H, et al. Baicalein alleviates diabetic peripheral neuropathy through inhibition of oxidative-nitrosative stress and p38 MAPK activation. Exp Neurol 2011; 230(1): 106-13.
[http://dx.doi.org/10.1016/j.expneurol.2011.04.002] [PMID: 21515260]
[140]
Liang YJ, Jian JH, Liu YC, et al. Advanced glycation end products-induced apoptosis attenuated by PPARdelta activation and epigallocatechin gallate through NF-kappaB pathway in human embryonic kidney cells and human mesangial cells. Diabetes Metab Res Rev 2010; 26(5): 406-16.
[http://dx.doi.org/10.1002/dmrr.1100] [PMID: 20583309]
[141]
Gothai S, Ganesan P, Park SY, Fakurazi S, Choi DK, Arulselvan P. Natural Phyto-Bioactive Compounds for the Treatment of Type 2 Diabetes: Inflammation as a Target. Nutrients 2016; 8(8): 461.
[http://dx.doi.org/10.3390/nu8080461] [PMID: 27527213]
[142]
Yang Z, Huang W, Zhang J, Xie M, Wang X. Baicalein improves glucose metabolism in insulin resistant HepG2 cells. Eur J Pharmacol 2019; 854: 187-93.
[http://dx.doi.org/10.1016/j.ejphar.2019.04.005] [PMID: 30970232]
[143]
Ma L, Li XP, Ji HS, Liu YF, Li EZ. Baicalein Protects Rats with Diabetic Cardiomyopathy Against Oxidative Stress and Inflammation Injury via Phosphatidylinositol 3-Kinase (PI3K)/AKT Pathway. Med Sci Monit 2018; 24: 5368-75.
[http://dx.doi.org/10.12659/MSM.911455] [PMID: 30070262]
[144]
Yin H, Huang L, Ouyang T, Chen L. Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-κB signaling pathway. Int Immunopharmacol 2018; 55: 55-62.
[http://dx.doi.org/10.1016/j.intimp.2017.12.002] [PMID: 29223854]
[145]
Noor A, Gunasekaran S, Vijayalakshmi MA. Improvement of Insulin Secretion and Pancreatic β-cell Function in Streptozotocin-induced Diabetic Rats Treated with Aloe vera Extract. Pharmacognosy Res 2017; 9(5)(Suppl. 1): S99-S104.
[http://dx.doi.org/10.4103/pr.pr_75_17] [PMID: 29333050]
[146]
Fu Z, Zhang W, Zhen W, et al. Genistein induces pancreatic beta- cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice. Endocrinology 2010; 151(7): 3026-37.
[http://dx.doi.org/10.1210/en.2009-1294] [PMID: 20484465]
[147]
Kawser Hossain M, Abdal Dayem A, Han J, et al. Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids. Int J Mol Sci 2016; 17(4): 569.
[http://dx.doi.org/10.3390/ijms17040569] [PMID: 27092490]
[148]
Fu Z, Gilbert ER, Pfeiffer L, Zhang Y, Fu Y, Liu D. Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes. Appl Physiol Nutr Metab 2012; 37(3): 480-8.
[http://dx.doi.org/10.1139/h2012-005] [PMID: 22509809]
[149]
Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52(1): 102-10.
[http://dx.doi.org/10.2337/diabetes.52.1.102] [PMID: 12502499]
[150]
Valsecchi AE, Franchi S, Panerai AE, Rossi A, Sacerdote P, Colleoni M. The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model. Eur J Pharmacol 2011; 650(2-3): 694-702.
[http://dx.doi.org/10.1016/j.ejphar.2010.10.060] [PMID: 21050844]
[151]
Das D, Sarkar S, Bordoloi J, Wann SB, Kalita J, Manna P. Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes. Biofactors 2018; 44(5): 407-17.
[http://dx.doi.org/10.1002/biof.1439] [PMID: 30191623]
[152]
Cheong SH, Furuhashi K, Ito K, et al. Daidzein promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and improves glucose homeostasis in Type 2 diabetic model mice. J Nutr Biochem 2014; 25(2): 136-43.
[http://dx.doi.org/10.1016/j.jnutbio.2013.09.012] [PMID: 24445037]
[153]
Alkhalidy H, Wang Y, Liu D. Dietary Flavonoids in the Prevention of T2D: An Overview. Nutrients 2018; 10(4): 438.
[http://dx.doi.org/10.3390/nu10040438] [PMID: 29614722]
[154]
Suantawee T, Elazab ST, Hsu WH, Yao S, Cheng H, Adisakwattana S. Cyanidin Stimulates Insulin Secretion and Pancreatic β-Cell Gene Expression through Activation of l-type Voltage-Dependent Ca2+ Channels. Nutrients 2017; 9(8): 814.
[http://dx.doi.org/10.3390/nu9080814] [PMID: 28788070]
[155]
Khoo HE, Azlan A, Tang ST, Lim SM. Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr Res 2017; 61(1)
[http://dx.doi.org/10.1080/16546628.2017.1361779] [PMID: 28970777]
[156]
Gharib A, Faezizadeh Z, Godarzee M. Treatment of diabetes in the mouse model by delphinidin and cyanidin hydrochloride in free and liposomal forms. Planta Med 2013; 79(17): 1599-604.
[http://dx.doi.org/10.1055/s-0033-1350908] [PMID: 24108435]
[157]
Vinayagam R, Xu B. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutr Metab (Lond) 2015; 12(1): 60.
[http://dx.doi.org/10.1186/s12986-015-0057-7] [PMID: 26705405]
[158]
Hidalgo J, Teuber S, Morera FJ, et al. Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40. Int J Mol Sci 2017; 18(4): 750.
[http://dx.doi.org/10.3390/ijms18040750] [PMID: 28379159]
[159]
Harini R, Pugalendi KV. Antioxidant and antihyperlipidaemic activity of protocatechuic acid on streptozotocin-diabetic rats. Redox Rep 2010; 15(2): 71-80.
[http://dx.doi.org/10.1179/174329210X12650506623285] [PMID: 20500988]
[160]
Bailey CJ. Metformin: historical overview. Diabetologia 2017; 60(9): 1566-76.
[http://dx.doi.org/10.1007/s00125-017-4318-z] [PMID: 28776081]
[161]
Sancho RAS, Pastore GM. Evaluation of the Effects of Anthocyanins in Type 2 Diabetes. Food Res Int 2012; 46(1): 378-86.
[http://dx.doi.org/10.1016/j.foodres.2011.11.021]
[162]
Zi F, Zi H, Li Y, He J, Shi Q, Cai Z. Metformin and cancer: An existing drug for cancer prevention and therapy. Oncol Lett 2018; 15(1): 683-90.
[PMID: 29422962]
[163]
Zheng Z, Zhu W, Yang B, et al. The co-treatment of metformin with flavone synergistically induces apoptosis through inhibition of PI3K/AKT pathway in breast cancer cells. Oncol Lett 2018; 15(4): 5952-8.
[http://dx.doi.org/10.3892/ol.2018.7999] [PMID: 29552226]
[164]
Jiang M, Li Z, Zhu G. Immunological regulatory effect of flavonoid baicalin on innate immune toll-like receptors. Pharmacol Res 2020; 158: 104890.
[http://dx.doi.org/10.1016/j.phrs.2020.104890] [PMID: 32389860]
[165]
Peng J, Li Q, Li K, et al. Quercetin Improves Glucose and Lipid Metabolism of Diabetic Rats: Involvement of Akt Signaling and SIRT1. J Diabetes Res 2017; 2017: e3417306.
[http://dx.doi.org/10.1155/2017/3417306] [PMID: 29379801]
[166]
Puzio-Kuter AM. The Role of p53 in Metabolic Regulation. Genes Cancer 2011; 2(4): 385-91.
[http://dx.doi.org/10.1177/1947601911409738] [PMID: 21779507]
[167]
Testa R, Bonfigli AR, Genovese S, De Nigris V, Ceriello A. The Possible Role of Flavonoids in the Prevention of Diabetic Complications. Nutrients 2016; 8(5): 310.
[http://dx.doi.org/10.3390/nu8050310] [PMID: 27213445]
[168]
Caro-Ordieres T, Marín-Royo G, Opazo-Ríos L, et al. The Coming Age of Flavonoids in the Treatment of Diabetic Complications. J Clin Med 2020; 9(2): 346.
[http://dx.doi.org/10.3390/jcm9020346] [PMID: 32012726]
[169]
Bugel SM, Bonventre JA, Tanguay RL. Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System. Toxicol Sci 2016; 154(1): 55-68.
[http://dx.doi.org/10.1093/toxsci/kfw139] [PMID: 27492224]
[170]
Sahu SC, Gray GC. Lipid peroxidation and DNA damage induced by morin and naringenin in isolated rat liver nuclei. Food Chem Toxicol 1997; 35(5): 443-7.
[http://dx.doi.org/10.1016/S0278-6915(97)00011-2] [PMID: 9216742]
[171]
Strick R, Strissel PL, Borgers S, Smith SL, Rowley JD. Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proc Natl Acad Sci USA 2000; 97(9): 4790-5.
[http://dx.doi.org/10.1073/pnas.070061297] [PMID: 10758153]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy