Abstract
The development of drugs possessing anti-diabetic activities is a long pursued goal in drug discovery. It has been shown that deregulated insulin mediated signaling, oxidative stress, obesity, and β-cell dysfunction are the main factors responsible for the disease. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can effectively treat diabetes by targeting different pathways has re-bloomed. Current anti-diabetic therapy is based on synthetic drugs that very often have side effects. For this reason, there is an instantaneous need to develop or search new alternatives. Recently, more attention is being paid to the study of natural products. Their huge advantage is that they can be ingested in everyday diet. Here, we discuss various causes, putative targets, and treatment strategies, mechanistic aspects as well as structural features with a particular focus on naturally occurring flavonoids as promising starting points for anti-diabetic led development.
Keywords: β-cells, diabetes mellitus, flavonoids, insulin resistance, insulin, antidiabetic agents.
Graphical Abstract
[1]
Southerland, J.H.; Taylor, G.W.; Moss, K.; Beck, J.D.; Offenbacher, S. Commonality in chronic inflammatory diseases: Periodontitis, diabetes, and coronary artery disease. Periodontology, 2006, 40(1), 130-143.
[2]
Powers, M.A.; Bardsley, J.; Cypress, M.; Duker, P.; Funnell, M.M.; Fischl, A.H.; Maryniuk, M.D.; Siminerio, L.; Vivian, E. Diabetes self-management education and support in type 2 diabetes: A joint position statement of the american diabetes association, the american association of diabetes educators, and the academy of nutrition and dietetics. Diabetes Educ., 2017, 43(1), 40-53.
[3]
Association, A.D. Classification and diagnosis of diabetes. Diabetes Care, 2017, 40(Suppl. 1), 11-24.
[4]
Patel, D.; Prasad, S.; Kumar, R.; Hemalatha, S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac. J. Trop. Biomed., 2012, 2(4), 320-330.
[5]
Pfeifer, M.A.; Halter, J.B.; Porte, D. Insulin secretion in diabetes mellitus. Am. J. Med., 1981, 70, 579-588.
[6]
Asmat, U.; Abad, K.; Ismail, K. Diabetes mellitus and oxidative stress—A concise review. Saudi Pharm. J., 2016, 24, 547-553.
[7]
Grodsky, G.M.; Anderson, C.E.; Coleman, D.L.; Craighead, J.E.; Gerritsen, G.C.; Hansen, C.T.; Herberg, L.; Howard, C.F.; Lernmark, A.; Matschinsky, F.M.; Rayfield, E.; Riley, W.J.; Rossini, A.A. Metabolic and underlying causes of diabetes mellitus. Diabetes, 1982, 31, 45-53.
[8]
Saisho, Y. β-cell dysfunction: Its critical role in prevention and management of type 2 diabetes. World J. Diabetes, 2015, 6, 109-124.
[9]
Ottosson Laakso, E.; Krus, U.; Storm, P.; Prasad, R.B.; Oskolkov, N.; Ahlqvist, E.; Fadista, J.; Hansson, O.; Groop, L.; Vikman, P. Glucose-induced Changes in Gene Expression in Human Pancreatic Islets – Causes or Consequences of Chronic Hyperglycemia. Diabetes, 2017, 67(4), 1-54.
[10]
Hajiaghaalipour, F.; Khalilpourfarshbafi, M.; Arya, A. Modulation of glucose transporter protein by dietary flavonoids in type 2 diabetes mellitus. Int. J. Innovations Biol. Chem. Sci., 2015, 11(5), 508-524.
[11]
Chaudhury, A.; Duvoor, C.; Dendi, V.S.R.; Kraleti, S.; Chada, A.; Ravilla, R.; Marco, A.; Shekhawat, N.S.; Montales, M.T.; Kuriakose, K. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management. Front. Endocrinol., 2017, 8.
[12]
Jia, W.; Gao, W.; Tang, L. Antidiabetic herbal drugs officially approved in China. Phytother. Res., 2003, 17(10), 1127-1134.
[13]
Hays, N.P.; Galassetti, P.R.; Coker, R.H. Prevention and treatment of type 2 diabetes: Current role of lifestyle, natural product, and pharmacological interventions. Pharmacol. Ther., 2008, 118(2), 181-191.
[14]
Ayepola, O.R.; Brooks, N.L.; Oguntibeju, O.O. Oxidative Stress
and Diabetic Complications: the role of antioxidant vitamins and
flavonoids. 2014. Antioxidant-Antidiabetic Agents and Human
Health. Intech publishers. Pp. 25-58
[15]
King, H.; Aubert, R.E.; Herman, W.H. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care, 1998, 21(9), 1414-1431.
[16]
Lakshmi, A.V.; Krishna, M.R.; Gutta, R.K. Insulin resistance, beta cell dysfunction, lipid profile, HOMA-R, HOMA-B. Insulin resistance, beta cell function and lipid profile in metabolic syndrome and type 2 diabetes mellitus. J. Evol. Res. Med. Biochem., 2015, 6, 14-17.
[17]
Guariguata, L.; Whiting, D.; Hambleton, I.; Beagley, J.; Linnenkamp, U.; Shaw, J. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res. Clin. Pract., 2014, 103(2), 137-149.
[18]
Croteau, R.; Kutchan, T.M.; Lewis, N.G. Natural products (secondary metabolites). Biochem. Mol. Biol. Plants, 2000, 24, 1250-1319.
[19]
Carpino, P.A.; Goodwin, B. Diabetes area participation analysis: a review of companies and targets described in the 2008-2010 patent literature. Expert Opin. Ther. Pat., 2010, 20(12), 1627-1651.
[21]
Chamberlain, J.J.; Rhinehart, A.S.; Shaefer, C.F.; Neuman, A. Diagnosis and management of diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann. Intern. Med., 2016, 164(8), 542-552.
[22]
Modak, M.; Dixit, P.; Londhe, J.; Ghaskadbi, S.; Devasagayam, T.P.A. Indian herbs and herbal drugs used for the treatment of diabetes. J. Clin. Biochem. Nutr., 2007, 40, 163-173.
[23]
Hussain, S.A.; Marouf, B. Flavonoids as alternatives in treatment of type 2 diabetes mellitus. Acad. J. Med. Plants, 2013, 1, 31-36.
[24]
Nabavi, S.; Habtemariam, S.; Daglia, M.; Shafighi, N.; Barber, A.; Nabavi, S. Anthocyanins as a potential therapy for diabetic retinopathy. Curr. Med. Chem., 2015, 22, 51-58.
[25]
Cazarolli, L.H.; Folador, P.; Moresco, H.H.; Brighente, I.M.C.; Pizzolatti, M.G.; Silva, F.R.M.B. Stimulatory effect of apigenin-6-C-β-L-fucopyranoside on insulin secretion and glycogen synthesis. Eur. J. Med. Chem., 2009, 44, 4668-4673.
[26]
Talaviya, P.A.; Rao, S.K.; Vyas, B.M.; Indoria, S.P.; Suman, R.K.; Suvagiya, V.P. A review on: Potential antidiabetic herbal medicines. Int. J. Pharm. Sci. Res., 2014, 5(2), 302-319.
[27]
Tapas, A.; Sakarkar, D.; Kakde, R. Flavonoids as nutraceuticals: A review. Trop. J. Pharm. Res., 2008, 7(3), 1089-1099.
[28]
Lavie, N.; Shukia, P.; Panchal, A. Role of flavonoids and saponins in the treatment of diabetes mellitus. J. Pharm. Sci. Bio. Sci. Res., 2016, 6(4), 535-541.
[29]
Crozier, A.; Jaganath, I.B.; Clifford, M.N. Dietary phenolics: Chemistry, bioavailability and effects on health. Nat. Prod. Rep., 2009, 26(8), 1001-1043.
[30]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: An overview. Scientif. World J., 2013, 2013
[http://dx.doi.org/10.1155/2013/162750]
[http://dx.doi.org/10.1155/2013/162750]
[31]
Singla, R.; Jaitak, V. Shatavari (asparagus racemosus wild): A review on its cultivation, morphology, phytochemistry and pharmacological importance. Int. J. Pharm. Sci. Res., 2014, 5(3), 730-741.
[32]
Cook, N.; Samman, S. Flavonoids—chemistry, metabolism, cardioprotective effects, and dietary sources. J. Nutr. Biochem., 1996, 7(2), 66-76.
[33]
Bahadoran, Z.; Mirmiran, P.; Azizi, F. Dietary polyphenols as potential nutraceuticals in management of diabetes: A review. J. Diabetes Metab. Disord., 2013, 12(1), 1.
[34]
Tanveer, A.; Akram, K.; Farooq, U.; Hayat, Z.; Shafi, A. Management of diabetic complications through fruit flavonoids as a natural remedy. Crit. Rev. Food Sci. Nutr., 2017, 57(7), 1411-1422.
[35]
Rasines-Perea, Z.; Teissedre, P.L. Grape polyphenols’ effects in human cardiovascular diseases and diabetes. Molecules, 2017, 22(1), 68-87.
[36]
Testa, R.; Bonfigli, A.; Genovese, S.; De Nigris, V.; Ceriello, A. The possible role of flavonoids in the prevention of diabetic complications. Nutrients, 2016, 8(5), 310.
[37]
Nicolle, E.; Souard, F.; Faure, P.; Boumendjel, A. Flavonoids as promising lead compounds in type 2 diabetes mellitus: Molecules of interest and structure-activity relationship. Curr. Med. Chem., 2011, 18(17), 2661-2672.
[38]
Zhao, Y.; Chen, B.; Shen, J.; Wan, L.; Zhu, Y.; Yi, T.; Xiao, Z. The beneficial effects of quercetin, curcumin, and resveratrol in obesity. Oxid. Med. Cell. Longev., 2017, 2017, 1459497.
[39]
Alipour, M.; Reza, M.; Hosseini, S.A.; Abbasnezhad, A.; Ghavami, A.; Shahmohammadi, H.A.; Ghanavati, M. The effects of catechins on related risk factors with type 2 diabetes: A review. Prog. Nutr., 2018, 20(1), 12-20.
[40]
Azzini, E.; Giacometti, J.; Russo, G.L. Antiobesity effects of anthocyanins in preclinical and clinical studies. Oxid. Med. Cell. Longev., 2017, 2017, 1-11.
[41]
Blumberg, J.B.; Camesano, T.A.; Cassidy, A.; Etherton, P.K. Cranberries and their bioactive constituents in human health. Adv. Nutr., 2013, 4, 618-632.
[42]
Alkhalidy, H.; Wang, Y.; Liu, D. Dietry flavonoids in the prevention of T2D: An overview. Nutrients, 2018, 8(438), 1-33.
[43]
Mohamed, E.A.H.; Siddiqui, M.J.A.; Ang, L.F.; Sadikun, A.; Chan, S.H.; Tan, S.C.; Asmawi, M.Z.; Yam, M.F. Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism. BMC Complement. Altern. Med., 2012, 12(1), 176.
[44]
Thorens, B. Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes. Am. J. Physiol. Gastrointest. Liver Physiol., 1996, 270(4), 541-553.
[45]
Deacon, C.F.; Holst, J.J. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: Comparison, efficacy and safety. Expert Opin. Pharmacother., 2013, 14(15), 2047-2058.
[46]
Chen, Y.G.; Li, P.; Li, P.; Yan, R.; Zhang, X.Q.; Wang, Y.; Zhang, X.T.; Ye, W.C.; Zhang, Q.W. α-Glucosidase inhibitory effect and simultaneous quantification of three major flavonoid glycosides in Microctis folium. Molecules, 2013, 18(4), 4221-4232.
[47]
Islam, M.N.; Jung, H.A.; Sohn, H.S.; Kim, H.M.; Choi, J.S. Potent α-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris. Arch. Pharm. Res., 2013, 36(5), 542-552.
[48]
Bräunlich, M.; Slimestad, R.; Wangensteen, H.; Brede, C.; Malterud, K.E.; Barsett, H. Extracts, anthocyanins and procyanidins from Aronia melanocarpa as radical scavengers and enzyme inhibitors. Nutrients, 2013, 5(3), 663-678.
[49]
Brahmachari, A.G. Bio-flavonoids with promising antidiabetic potentials: A critical survey. Opportunity, challenge and scope of natural products in medicinal chemistry. Res. Signpost., 2011, 2, 187-212.
[50]
Tabopda, T.K.; Ngoupayo, J.; Awoussong, P.K.; Mitaine-Offer, A.C.; Ali, M.S.; Ngadjui, B.T.; Lacaille-Dubois, M.A. Triprenylated flavonoids from Dorstenia psilurus and their α-Glucosidase Inhibition Properties. J. Nat. Prod., 2008, 71(12), 2068-2072.
[51]
Nishioka, T.; Kawabata, J.; Aoyama, Y. Baicalein, an α-glucosidase inhibitor from Scutellaria baicalensis. J. Nat. Prod., 1998, 61(11), 1413-1415.
[52]
Li, J.M.; Che, C.T.; Lau, C.; Leung, P.S.; Cheng, C.H. Inhibition of intestinal and renal Na+ glucose cotransporter by naringenin. Int. J. Biochem. Cell Biol., 2006, 38(5), 985-995.
[53]
Konaté, K.; Yomalan, K.; Sytar, O.; Zerbo, P.; Brestic, M.; Patrick, V.D.; Gagniuc, P.; Barro, N. Free radicals scavenging capacity, antidiabetic and antihypertensive activities of flavonoid rich fractions from leaves of Trichilia emetica and Opilia amentacea in an animal model of type 2 diabetes mellitus. J. Evid. Based Complementary Altern. Med., 2014, 2014, 13.
[54]
Lo Piparo, E.; Scheib, H.; Frei, N.; Williamson, G.; Grigorov, M.; Chou, C.J. Flavonoids for controlling starch digestion: Structural requirements for inhibiting human α-amylase. J. Med. Chem., 2008, 51(12), 3555-3561.
[55]
Jain, C.; Singh, A.; Kumar, P.; Gautam, K. Anti-diabetic potential of flavonoids and other crude extracts of stem bark of Mangifera indica Linn: A comparative study. J. Sci. Inn. Res., 2014, 3(1), 21-27.
[56]
Ibrahim, S.; Al-Ahdal, A.; Khedr, A.; Mohamed, G. Antioxidant α-amylase inhibitors flavonoids from Iris germanica rhizomes. Rev. Bras. Farmacogn., 2017, 27(2), 170-174.
[57]
Schulze, C.; Bangert, A.; Schwanck, B.; Vollert, H.; Blaschek, W.; Daniel, H. Extracts and flavonoids from onion inhibit the intestinal sodium-coupled glucose transporter 1 (SGLT1) in vitro but show no anti-hyperglycaemic effects in vivo in normoglycaemic mice and human volunteers. J. Funct. Foods, 2015, 18, 117-128.
[58]
Kwon, O.; Eck, P.; Chen, S.; Corpe, C.P.; Lee, J.H.; Kruhlak, M.; Levine, M. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. FASEB J., 2007, 21(2), 366-377.
[59]
Bharucha, B.; Dwivedi, M.; Laddha, N.; Begum, R.; Hardikar, A.; Ramachandran, A. Antioxidant rich flavonoids from Oreocnide integrifolia enhance glucose uptake and insulin secretion and protects pancreatic β-cells from streptozotocin insult. BMC Complement. Altern. Med., 2011, 11(1), 126.
[60]
Bansal, P.; Paul, P.; Mudgal, J.; Nayak, G.P.; Thomas Pannakal, S.; Priyadarsini, K.; Unnikrishnan, M. Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice. Exp. Toxicol. Pathol., 2012, 64(6), 651-658.
[61]
Maity, S.; Mukhopadhyay, P.; Kundu, P.P.; Chakraborti, A.S. Alginate coated chitosan core-shell nanoparticles for efficient oral delivery of naringenin in diabetic animals—An in vitro and in vivo approach. Carbohydr. Polym., 2017, 170, 124-132.
[62]
Consoli, A.; Nurjhan, N.; Reilly, J., Jr; Bier, D.; Gerich, J. Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism. J. Clin. Invest., 1990, 86(6), 2038-2045.
[63]
Dinneen, S.; Gerich, J.; Rizza, R. Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N. Engl. J. Med., 1992, 327(10), 707-713.
[64]
Yan, S.; Zhang, Q.; Zhong, X.; Tang, J.; Wang, Y.; Yu, J.; Zhou, Y.; Zhang, J.; Guo, F.; Liu, Y. Prostanoid receptor mediated inflammatory pathway promotes hepatic gluconeogenesis through activation of PKA and inhibition of AKT. Diabetes, 2014, 63(9), 2911-2923.
[65]
Prasath, G.S.; Subramanian, S.P. Fisetin, a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats. Food Chem. Toxicol., 2013, 59, 249-255.
[66]
Prasath, G.S.; Pillai, S.I.; Subramanian, S.P. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats. Eur. J. Pharmacol., 2014, 740, 248-254.
[67]
Al-Numair, K.; Alsaif, M.; Govindasamy, C. Kaempferol, a dietary
flavonoid improves glucose homeostasis in streptozotocin diabetic
tissues by altering glycolytic and gluconeogenic enzymes. Endocrine
Abs, 2014, 13-49.
[68]
Yan, F.; Zhang, J.; Zhang, L.; Zheng, X. Mulberry anthocyanin extract regulates glucose metabolism by promotion of glycogen synthesis and reduction of gluconeogenesis in human HepG2 cells. Food Funct., 2016, 7(1), 425-433.
[69]
Kato, A.; Nasu, N.; Takebayashi, K.; Adachi, I.; Minami, Y.; Sanae, F.; Asano, N.; Watson, A.A.; Nash, R.J. Structure-Activity relationships of flavonoids as potential inhibitors of glycogen phosphorylase. J. Agric. Food Chem., 2008, 56, 4469-4473.
[70]
Xiao, J.; Ni, X.; Kai, G.; Chen, X. Advance in dietary polyphenols as aldose reductases inhibitors: Structure-activity relationship aspect. Crit. Rev. Food Sci. Nutr., 2015, 55(1), 16-31.
[71]
Ben Hmidene, A.; Smaoui, A.; Abdelly, C.; Isoda, H.; Shigemori, H. Effect of O-methylated and glucuronosylated flavonoids from Tamarix gallica on α-glucosidase inhibitory activity: Structure–activity relationship and synergistic potential. Biosci. Biotechnol. Biochem., 2017, 81(3), 445-448.
[72]
Park, K.H.; Yoon, K.H.; Yin, J.; Le, T.T.; Ahn, H.S.; Yoon, S.H.; Lee, M.W. Antioxidative and anti-inflammatory activities of galloyl derivatives and antidiabetic activities of acer ginnala. J. Evid. Based Complementary Altern. Med., 2017, 2017, 8.
[73]
Sheliya, M.A.; Rayhana, B.; Ali, A.; Pillai, K.K.; Aeri, V.; Sharma, M.; Mir, S.R. Inhibition of α-glucosidase by new prenylated flavonoids from euphorbia hirta L. herb. J. Ethnopharmacol., 2015, 176, 1-8.
[74]
Henquin, J.C. The dual control of insulin secretion by glucose involves triggering and amplifying pathways in β-cells. Diabetes Res. Clin. Pract., 2011, 93, 27-31.
[75]
Ebina, Y.; Ellis, L.; Jarnagin, K.; Edery, M.; Graf, L.; Clauser, E.; Ou, J-h.; Masiarz, F.; Kan, Y.; Goldfine, I. The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signalling. Cell, 1985, 40(4), 747-758.
[76]
Cusi, K.; Maezono, K.; Osman, A.; Pendergrass, M.; Patti, M.E.; Pratipanawatr, T.; DeFronzo, R.A.; Kahn, C.R.; Mandarino, L.J. Insulin resistance differentially affects the PI 3-kinase–and MAP kinase–mediated signaling in human muscle. J. Clin. Invest., 2000, 105(3), 311-320.
[77]
Saltiel, A.R.; Pessin, J.E. Insulin signaling pathways in time and space. Trends Cell Biol., 2002, 12(2), 65-71.
[78]
Rains, J.L.; Jain, S.K. Oxidative stress, insulin signaling, and diabetes. Free Radic. Biol. Med., 2011, 50(5), 567-575.
[79]
Sopasakis, V.R.; Liu, P.; Suzuki, R.; Kondo, T.; Winnay, J.; Tran, T.T.; Asano, T.; Smyth, G.; Sajan, M.P.; Farese, R.V. Specific roles of the p110α isoform of phosphatidylinsositol 3-kinase in hepatic insulin signaling and metabolic regulation. Cell Metab., 2010, 11(3), 220-230.
[80]
Saltiel, A.R.; Pessin, J.E. Insulin signaling pathways in time and space. Trends Cell Biol., 2002, 12(2), 65-71.
[81]
Jiang, G.; Zhang, B.B. Pi 3-kinase and its up-and down-stream modulators as potential targets for the treatment of type II diabetes. Front. Biosci.: J. Virt. Lib., 2002, 7, 903-907.
[82]
Kwon, H.; Pessin, J.E. Adipokines mediate inflammation and insulin resistance. Front. Endocrinol., 2013, 4, 1-13.
[83]
Gupte, A.; Mora, S. Activation of the Cbl insulin signaling pathway in cardiac muscle; dysregulation in obesity and diabetes. Biochem. Biophys. Res. Commun., 2006, 342(3), 751-757.
[84]
Zabolotny, J.M.; Bence-Hanulec, K.K.; Stricker-Krongrad, A.; Haj, F.; Wang, Y.; Minokoshi, Y.; Kim, Y.B.; Elmquist, J.K.; Tartaglia, L.A.; Kahn, B.B. PTP1B regulates leptin signal transduction in vivo. Dev. Cell, 2002, 2(4), 489-495.
[86]
Kimmel, B.; Inzucchi, S.E. Oral agents for type 2 diabetes: an update. Clin. Diabetes, 2005, 23, 64-76.
[87]
Evans, J.L.; Goldfine, I.D.; Maddux, B.A.; Grodsky, G.M. Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of type 2 diabetes. Endocr. Rev., 2002, 23(5), 599-622.
[88]
Montagut, G.; Bladé, C.; Blay, M.; Fernández-Larrea, J.; Pujadas, G.; Salvadó, M.J.; Arola, L.; Pinent, M.; Ardévol, A. Effects of a grapeseed procyanidin extract (GSPE) on insulin resistance. J. Nutr. Biochem., 2010, 21(10), 961-967.
[89]
Babu, P.V.A.; Liu, D.; Gilbert, E.R. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J. Nutr. Biochem., 2013, 24(11), 1777-1789.
[90]
Luna Vital, D.; Weiss, M.; Mejia, E.G. Anthocyanins from purple corn ameliorated TNF‐α‐Induced inflammation and insulin resistance in 3T3‐L1 adipocytes via activation of insulin signaling and enhanced GLUT4 translocation. Mol. Nutr. Food Res., 2017, 61, 170036.
[91]
Namdeo, A. Plant cell elicitation for production of secondary metabolites: A review. Pharmacogn. Rev., 2007, 1(1), 69-79.
[92]
Hung, H.Y.; Qian, K.; Morri Natschke, S.L.; Hsu, C.S.; Lee, K.H. Recent discovery of plant-derived anti-diabetic natural products. Nat. Prod. Rep., 2012, 29(5), 580-606.
[93]
Akase, T.; Shimada, T.; Terabayashi, S.; Ikeya, Y.; Sanada, H.; Aburada, M. Antiobesity effects of Kaempferia parviflora in spontaneously obese type II diabetic mice. J. Nat. Med., 2011, 65(1), 73-80.
[94]
Li, R.W.; Theriault, A.G.; Au, K.; Douglas, T.D.; Casaschi, A.; Kurowska, E.M.; Mukherjee, R. Citrus polymethoxylated flavones improve lipid and glucose homeostasis and modulate adipocytokines in fructose-induced insulin resistant hamsters. Life Sci., 2006, 79, 365-373.
[95]
Cordero-Herrera, I.; Martín, M.Á.; Goya, L.; Ramos, S. Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells. Food Chem. Toxicol., 2014, 64, 10-19.
[96]
Hsu, C.Y.; Shih, H.Y.; Chia, Y.C.; Lee, C.H.; Ashida, H.; Lai, Y.K.; Weng, C.F. Rutin potentiates insulin receptor kinase to enhance insulin‐dependent glucose transporter 4 translocation. Mol. Nutr. Food Res., 2014, 58(6), 1168-1176.
[97]
Cazarolli, L.H.; Folador, P.; Pizzolatti, M.G.; Mena Barreto Silva, F.R. Signaling pathways of kaempferol-3-neohesperidoside in glycogen synthesis in rat soleus muscle. Biochimie, 2009, 91(7), 843-849.
[98]
Davis, J.; Higginbotham, A.; O’Connor, T.; Moustaid-Moussa, N.; Tebbe, A.; Kim, Y-C.; Cho, K.W.; Shay, N.; Adler, S.; Peterson, R. Soy protein and isoflavones influence adiposity and development of metabolic syndrome in the obese male ZDF rat. Ann. Nutr. Metab., 2007, 51(1), 42-52.
[99]
Mezei, O.; Banz, W.J.; Steger, R.W.; Peluso, M.R.; Winters, T.A.; Shay, N. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J. Nutr., 2003, 133(5), 1238-1243.
[100]
Cho, K.W.; Lee, O.H.; Banz, W.J.; Moustaid-Moussa, N.; Shay, N.F.; Kim, Y.C. Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARγ transcriptional activity. J. Nutr. Biochem., 2010, 21(9), 841-847.
[101]
Chen, L.; Li, Q.Y.; Shi, X.J.; Mao, S.L.; Du, Y.L. 6-Hydroxydaidzein enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. J. Agric. Food Chem., 2013, 61(45), 10714-10719.
[102]
Van Dam, R.M.; Naidoo, N.; Landberg, R. Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases: review of recent findings. Curr. Opin. Lipidol., 2013, 24(1), 25-33.
[103]
Cai, E.P.; Lin, J.K. Epigallocatechin gallate (EGCG) and rutin suppress the glucotoxicity through activating IRS2 and AMPK signaling in rat pancreatic β cells. J. Agric. Food Chem., 2009, 57(20), 9817-9827.
[104]
Matsuda, H.; Kogami, Y.; Nakamura, S.; Sugiyama, T.; Ueno, T.; Yoshikawa, M. Structural requirements of flavonoids for the adipogenesis of 3T3-L1 cells. Bioorg. Med. Chem., 2011, 19(9), 2835-2841.
[105]
Umamaheswari, M.; Aji, C.; Asokkumar, K.; Sivashanmugam, T.; Subhadradevi, V.; Jagannath, P.; Madeswaran, A. In silico docking studies of aldose reductase inhibitory activity of selected flavonoids. Int. J. Drug Dev. Res., 2012, 4, 328-334.
[106]
Jung, U.J.; Lee, M.K.; Park, Y.B.; Kang, M.; Choi, M.S. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int. J. Biochem. Cell Biol., 2006, 38(7), 1134-1145.
[107]
Mahmoud, A.M.; Ahmed, O.M.; Ashour, M.B.; Abdel-Moneim, A. In vivo and in vitro antidiabetic effects of citrus flavonoids; a study on the mechanism of action. Int. J. Diabetes Dev. Ctries., 2015, 35(3), 250-263.
[108]
Eid, H.M.; Martineau, L.C.; Saleem, A.; Muhammad, A.; Vallerand, D.; Benhaddou‐Andaloussi, A.; Nistor, L.; Afshar, A.; Arnason, J.T.; Haddad, P.S. Stimulation of AMP‐activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis‐idaea. Mol. Nutr. Food Res., 2010, 54(7), 991-1003.
[109]
Rayidi, S. Effect of Naringenin on carbohydrate metabolism in streptozotocin-nicotinamide induced diabetic rats. Biomirror, 2011, 2, 1-9.
[110]
Zygmunt, K.; Faubert, B.; MacNeil, J.; Tsiani, E. Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK. Biochem. Biophys. Res. Commun., 2010, 398(2), 178-183.
[111]
Cameron, A.R.; Anton, S.; Melville, L.; Houston, N.P.; Dayal, S.; McDougall, G.J.; Stewart, D.; Rena, G. Black tea polyphenols mimic insulin/insulin‐like growth factor‐1 signalling to the longevity factor FOXO1a. Aging Cell, 2008, 7(1), 69-77.
[112]
Li, W.; Li, S.; Higai, K.; Sasaki, T.; Asada, Y.; Ohshima, S.; Koike, K. Evaluation of licorice flavonoids as protein tyrosine phosphatase 1B inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(21), 5836-5839.
[113]
Wajchenberg, B.L.; Cohen, R.V. Adipose Tissue and Type 2 Diabetes
Mellitus. In Adipose Tissue and Adipokines in Health and
Disease. Springer. Humana Press, Totowa, NJ; 2014, pp. 235-248.
[114]
Blüher, M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract. Res. Clin. Endocrinol. Metab., 2013, 27(2), 163-177.
[115]
Fan, J.; Johnson, M.H.; Lila, M.A.; Yousef, G.; de Mejia, E.G. Berry and citrus phenolic compounds inhibit dipeptidyl peptidase IV: Implications in diabetes management. J. Evid. Based Complementary Altern. Med., 2013, 2013, 1-13.
[116]
Dai, X.; Ding, Y.; Zhang, Z.; Cai, X.; Bao, L.; Li, Y. Quercetin but not quercitrin ameliorates tumor necrosis factor-alpha-induced insulin resistance in C2C12 skeletal muscle cells. Biol. Pharm. Bull., 2013, 36(5), 788-795.
[117]
Blüher, M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract. Res. Clin. Endocrinol. Metab., 2013, 27(2), 163-177.
[118]
Jarald, E.; Joshi, S.B.; Jain, D.C. Diabetes and herbal medicines. Iran J. Pharmacol. Ther., 2008, 7, 97-106.
[119]
Association, A.D. Obesity management for the treatment of type 2 diabetes. Diabetes Care, 2016, 39(Suppl. 1), 47-51.
[120]
Pan, M.H.; Lai, C.S.; Ho, C.T. Anti-inflammatory activity of natural dietary flavonoids. Food Funct., 2010, 1(1), 15-31.
[121]
Aguirre, L.; Arias, N.; Macarulla, M.T.; Gracia, A.; Portillo, M.P. Beneficial effects of quercetin on obesity and diabetes. Open Nutraceuticals J., 2011, 4, 189-198.
[122]
Kobori, M.; Masumoto, S.; Akimoto, Y.; Oike, H. Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western‐style diet in C57/BL6J mice. Mol. Nutr. Food Res., 2011, 55(4), 530-540.
[123]
Ahn, J.; Lee, H.; Kim, S.; Park, J.; Ha, T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem. Biophys. Res. Commun., 2008, 373(4), 545-549.
[124]
Wein, S.; Behm, N.; Petersen, R.K.; Kristiansen, K.; Wolffram, S. Quercetin enhances adiponectin secretion by a PPAR-γ independent mechanism. Eur. J. Pharm. Sci., 2010, 41(1), 16-22.
[125]
Promson, N.; Puntheeranurak, S. Kaempferia parviflora Extract diminishes hyperglycemia and visceral fat accumulation in mice fed with high fat and high sucrose diet. J. Physiol., 2014, 27(1), 13-19.
[126]
Haytowitz, D.; Bhagwat, S.; Holden, J. Sources of variability in the flavonoid content of foods. Procedia Food Sci., 2013, 2, 46-51.
[127]
Pinent, M.; Bladé, C.; Salvadó, M.J.; Blay, M.; Pujadas, G.; Fernández-Larrea, J.; Arola, L.; Ardévol, A. Procyanidin effects on adipocyte-related pathologies. Crit. Rev. Food Sci. Nutr., 2006, 46(7), 543-550.
[128]
Ding, L.; Jin, D.; Chen, X. Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes. J. Nutr. Biochem., 2010, 21(10), 941-947.
[129]
Zang, Y.; Zhang, L.; Igarashi, K.; Yu, C. The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe soybean leaves in high-fat-diet mice. Food Funct., 2015, 6(3), 834-841.
[130]
Cokorinos, E.C.; Delmore, J.; Reyes, A.R.; Albuquerque, B.; Kjøbsted, R.; Jørgensen, N.O.; Tran, J.L.; Jatkar, A.; Cialdea, K.; Esquejo, R.M. Activation of skeletal muscle ampk promotes glucose disposal and glucose lowering in non-human primates and mice. Cell Metab., 2017, 25(5), 1147-1159.
[131]
Uddin, M.N.; Sharma, G.; Choi, H.S.; Lim, S.; Keun, W.O. AMPK activators from natural products: A patent review. Nat. Prod. Sci., 2013, 19(1), 1-7.
[132]
Friedman, M. Mushroom Polysaccharides: Chemistry and antiobesity, antidiabetes, anticancer, and antibiotic properties in cells, rodents, and humans. Foods, 2016, 5(4), 80-120.
[133]
Lee, J.W.; Choe, S.S.; Jang, H.; Kim, J.; Jeong, H.W.; Jo, H.; Jeong, K.H.; Tadi, S.; Park, M.G.; Kwak, T.H. AMPK activation with glabridin ameliorates adiposity and lipid dysregulation in obesity. J. Lipid Res., 2012, 53(7), 1277-1286.
[134]
Sharma, B.; Viswanath, G.; Salunke, R.; Roy, P. Effects of flavonoid-rich extract from seeds of Eugenia jambolana (L.) on carbohydrate and lipid metabolism in diabetic mice. Food Chem., 2008, 110(3), 697-705.
[135]
Tafesse, T.B.; Hymete, A.; Mekonnen, Y.; Tadesse, M. Antidiabetic activity and phytochemical screening of extracts of the leaves of Ajuga remota Benth on alloxan-induced diabetic mice. BMC Complement. Altern. Med., 2017, 17(1), 243.
[136]
Njangiru, I.; Gitimu, M.; Njagi, E. In Vivo antidiabetic activity of aqueous extract of psidium quajava in alloxanised diabetic mice. J. Med. Biomed. App. Sci., 2017, 5(1), 1-6.
[137]
Srinivasan, S.; Pari, L. Antihyperlipidemic effect of diosmin: A citrus flavonoid on lipid metabolism in experimental diabetic rats. J. Funct. Foods, 2013, 5(1), 484-492.
[138]
Borradaile, N.M.; de Dreu, L.E.; Huff, M.W. Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. Diabetes, 2003, 52(10), 2554-2561.
[139]
Luo, P.; Tan, Z.H.; Zhang, Z.F.; Zhang, H.; Liu, X.F.; Mo, Z.J. Scutellarin isolated from Erigeron multiradiatus inhibits high glucose-mediated vascular inflammation. Yakugaku Zasshi, 2008, 128(9), 1293-1299.
[140]
Nabavi, S.F.; Russo, G.L.; Daglia, M.; Nabavi, S.M. Role of quercetin as an alternative for obesity treatment: you are what you eat! Food Chem., 2015, 179, 305-310.
[141]
Park, J.H.; Bae, J.H.; Im, S.S.; Song, D.K. Green tea and type 2 diabetes. Integr. Med. Res., 2014, 3(1), 4-10.
[142]
Eriksson, J.W. Metabolic stress in insulin’s target cells leads to ROS accumulation–a hypothetical common pathway causing insulin resistance. FEBS Lett., 2007, 581(19), 3734-3742.
[143]
Inzucchi, S.E.; Bergenstal, R.M.; Buse, J.B.; Diamant, M.; Ferrannini, E.; Nauck, M.; Peters, A.L.; Tsapas, A.; Wender, R.; Matthews, D.R. Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the american diabetes association and the european association for the study of diabetes. Diabetes Care, 2015, 38(1), 140-149.
[144]
Maritim, A.; Sanders, R.; Watkins, R.J. Diabetes, oxidative stress, and antioxidants: A review. J. Biochem. Mol. Toxicol., 2003, 17(1), 24-38.
[145]
Robertson, R.P. Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J. Biol. Chem., 2004, 279(41), 42351-42354.
[146]
Davis, S. Oral hypoglycaemic drugs for the treatment of type 2 diabetes mellitus review. S. Afr. Pharm. J., 2012, 79(3), 22-26.
[147]
Fernández-Mejía, C. Oxidative stress in diabetes mellitus and the
role of vitamins with antioxidant actions. Oxidative stress and
chronic degenerative diseases-a role for antioxidants, 2013, In-Tech, Rijeka, 209.
[148]
Evans, J.L.; Goldfine, I.D.; Maddux, B.A.; Grodsky, G.M. Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of type 2 diabetes. Endocr. Rev., 2002, 23(5), 599-622.
[149]
Kawamura, M.; Heinecke, J.W.; Chait, A. Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway. J. Clin. Invest., 1994, 94(2), 771-778.
[150]
Martins, A.R.; Nachbar, R.T.; Gorjao, R.; Vinolo, M.A.; Festuccia, W.T.; Lambertucci, R.H.; Cury-Boaventura, M.F.; Silveira, L.R.; Curi, R.; Hirabara, S.M. Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: Importance of the mitochondrial function. Lipids Health Dis., 2012, 11(30), 1-11.
[151]
Matough, F.A.; Budin, S.B.; Hamid, Z.A.; Alwahaibi, N.; Mohamed, J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ. Med. J., 2012, 12(1), 5-18.
[152]
Jaitak, V.; Kaul, V.K.; Kumar, N.; Singh, B.; Dhar, J.; Sharma, O. New hopane triterpenes and antioxidant constituents from Potentilla fulgens. Nat. Prod. Commun., 2010, 5(10), 1561-1566.
[153]
Prasath, G.S.; Subramanian, S.P. Fisetin, a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats. Food Chem. Toxicol., 2013, 59, 249-255.
[154]
Miyake, Y.; Yamamoto, K.; Tsujihara, N.; Osawa, T. Protective effects of lemon flavonoids on oxidative stress in diabetic rats. Lipids, 1998, 33(7), 689-695.
[155]
Dias, A.S.; Porawski, M.; Alonso, M.; Marroni, N.; Collado, P.S.; González-Gallego, J. Quercetin decreases oxidative stress, NF-κB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats. J. Nutr., 2005, 135(10), 2299-2304.
[156]
Lukačínová, A.; Mojžiš, J.; Beňačka, R.; Keller, J.; Maguth, T.; Kurila, P.; Vaško, L.; Rácz, O.; Ništiar, F. Preventive effects of flavonoids on alloxan-induced diabetes mellitus in rats. Acta Vet. Brno, 2008, 77(2), 175-182.
[157]
Prabhakar, P.; Kumar, A.; Doble, M. Combination therapy: A new strategy to manage diabetes and its complications. Phytomedicine, 2014, 21(2), 123-130.
[158]
Jung, S.H.; Lee, J.M.; Lee, H.J.; Kim, C.Y.; Lee, E.H.; Um, B.H. Aldose reductase and advanced glycation endproducts inhibitory effect of Phyllostachys nigra. Biol. Pharm. Bull., 2007, 30(8), 1569-1572.
[159]
Wirasathien, L.; Pengsuparp, T.; Suttisri, R.; Ueda, H.; Moriyasu, M.; Kawanishi, K. Inhibitors of aldose reductase and advanced glycation end-products formation from the leaves of Stelechocarpus cauliflorus RE Fr. Phytomedicine, 2007, 14(7), 546-550.
[160]
Yoo, N.H.; Jang, D.S.; Yoo, J.L.; Lee, Y.M.; Kim, Y.S.; Cho, J.H.; Kim, J.S. Erigeroflavanone, a flavanone derivative from the flowers of Erigeron annuus with protein glycation and aldose reductase inhibitory activity. J. Nat. Prod., 2008, 71(4), 713-715.
[161]
Kamalakkannan, N.; Prince, P.S.M. Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin‐induced diabetic wistar rats. Basic Clin. Pharmacol. Toxicol., 2006, 98(1), 97-103.
[162]
Patel, D.; Kumar, R.; Prasad, S.; Sairam, K.; Hemalatha, S. Antidiabetic and in vitro antioxidant potential of Hybanthus enneaspermus (Linn) F. Muell in streptozotocin–induced diabetic rats. Asian Pac. J. Trop. Biomed., 2011, 1(4), 316-322.
[163]
Yao, X.; Zhu, L.; Chen, Y.; Tian, J.; Wang, Y. In vivo and in vitro antioxidant activity and α-glucosidase, α-amylase inhibitory effects of flavonoids from Cichorium glandulosum seeds. Food Chem., 2013, 139, 59-66.
[164]
Fawzy, G.A.; Abdallah, H.M.; Marzouk, M.S.; Soliman, F.M.; Sleem, A.A. Antidiabetic and antioxidant activities of major flavonoids of Cynanchum acutum L.(Asclepiadaceae) growing in Egypt. Z. Naturforsch. C Bio. Sci., 2008, 63(9-10), 658-662.
[165]
de Sousa, E.; Zanatta, L.; Seifriz, I.; Creczynski-Pasa, T.B.; Pizzolatti, M.G.; Szpoganicz, B.; Silva, F.R.M.B. Hypoglycemic effect and antioxidant potential of kaempferol-3, 7-O-(α)-dirhamnoside from Bauhinia f orficata Leaves. J. Nat. Prod., 2004, 67(5), 829-832.
[166]
Matsuda, H.; Morikawa, T.; Toguchida, I.; Yoshikawa, M. Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity. Chem. Pharm. Bull., 2002, 50(6), 788-795.
[167]
Coman, C.; Rugina, O.D.; Socaciu, C. Plants and natural compounds with antidiabetic action. Not. Bot. Horti Agrobot. Cluj-Napoca, 2012, 40(1), 314-325.
[168]
Rauter, A.P.; Martins, A.; Borges, C.; Mota‐Filipe, H.; Pinto, R.; Sepodes, B.; Justino, J. Antihyperglycaemic and protective effects of flavonoids on streptozotocin–induced diabetic rats. Phytother. Res., 2010, 24(2), 133-138.
[169]
Testa, R.; Bonfigli, A.R.; Genovese, S.; De Nigris, V.; Ceriello, A. The possible role of flavonoids in the prevention of diabetic complications. Nutrients, 2016, 8(5), 310-323.
[170]
Luna, B.; Feinglos, M.N. Oral agents in the management of type 2 diabetes mellitus. Am. Fam. Physician, 2001, 63(9), 1747-1756.
[171]
Wu, C.H.; Yen, G.C. Inhibitory effect of naturally occurring flavonoids on the formation of advanced glycation endproducts. J. Agric. Food Chem., 2005, 53(8), 3167-3173.
[172]
Choi, S.K.; Zhang, X.H.; Seo, J.S. Suppression of oxidative stress by grape seed supplementation in rats. Nutr. Res. Pract., 2012, 6(1), 3-8.
[173]
Sak, K. Dependence of DPPH radical scavenging activity of dietary flavonoid quercetin on reaction environment. Mini Rev. Med. Chem., 2014, 14(6), 494-504.
[174]
Association, A.D. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2010, 33(Suppl. 1), 62-69.
[175]
Cazarolli, L.H.; Zanatta, L.; Alberton, E.H.; Reis Bonorino Figueiredo, M.S.; Folador, P.; Damazio, R.G.; Pizzolatti, M.G.; Mena Barreto Silva, F.R. Flavonoids: Cellular and molecular mechanism of action in glucose homeostasis. Mini Rev. Med. Chem., 2008, 8(10), 1032-1038.
[176]
Chang-Chen, K.; Mullur, R.; Bernal-Mizrachi, E. β-cell failure as a complication of diabetes. Rev. Endocr. Metab. Disord., 2008, 9(4), 329-343.
[177]
Leong, K.S.; Wilding, J.P. Obesity and diabetes. Best Pract. Res. Clin. Endocrinol. Metab., 1999, 13(2), 221-237.
[178]
Vetere, A.; Choudhary, A.; Burns, S.M.; Wagner, B.K. Targeting the pancreatic β-cell to treat diabetes. Nat. Rev. Drug Discov., 2014, 13(4), 278-289.
[179]
Huang, C.; Florez, J.C. Pharmacogenetics in type 2 diabetes: potential implications for clinical practice. Genome Med., 2011, 3, 76.
[180]
LeRoith, D. β-cell dysfunction and insulin resistance in type 2 diabetes: Role of metabolic and genetic abnormalities. Am. J. Med., 2002, 113(6), 3-11.
[181]
Karunakaran, U.; Kim, H.J.; Kim, J.Y.; Lee, I.K. Guards and culprits in the endoplasmic reticulum: Glucolipotoxicity and β-cell failure in type II diabetes. Exp. Diabetes Res., 2011, 2012, 1-9.
[182]
Kaneto, H.; Kajimoto, Y.; Miyagawa, J.I.; Matsuoka, T.A.; Fujitani, Y.; Umayahara, Y.; Hanafusa, T.; Matsuzawa, Y.; Yamasaki, Y.; Hori, M. Beneficial effects of antioxidants in diabetes: Possible protection of pancreatic beta-cells against glucose toxicity. Diabetes, 1999, 48(12), 2398-2406.
[183]
Donath, M.Y.; Størling, J.; Maedler, K.; Mandrup-Poulsen, T. Inflammatory mediators and islet β-cell failure: A link between type 1 and type 2 diabetes. J. Mol. Med., 2003, 81(8), 455-470.
[184]
Martín, M.Á.; Fernández‐Millán, E.; Ramos, S.; Bravo, L.; Goya, L. Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function against oxidative stress. Mol. Nutr. Food Res., 2013, 1, 316-322.
[185]
Jayaprakasam, B.; Vareed, S.K.; Olson, L.K.; Nair, M.G. Insulin secretion by bioactive anthocyanins and anthocyanidins present in fruits. J. Agric. Food Chem., 2005, 53(1), 28-31.
[186]
Cazarolli, L.H.; Kappel, V.D.; Pereira, D.F.; Moresco, H.H.; Brighente, I.M.C.; Pizzolatti, M.G.; Silva, F.R.M.B. Anti-hyperglycemic action of apigenin-6-C-β-fucopyranoside from Averrhoa carambola. Fitoterapia, 2012, 83, 1176-1183.
[187]
Yang, W.; Wang, S.; Li, L.; Liang, Z.; Wang, L. Genistein reduces hyperglycemia and islet cell loss in a high-dosage manner in rats with alloxan-induced pancreatic damage. Pancreas, 2011, 40(3), 396-402.
[188]
Obasse, I.; Taylor, M.; Fullwood, N.J.; Allsop, D. Development of proteolytically stable N-methylated peptide inhibitors of aggregation of the amylin peptide implicated in type 2 diabetes. Interface Focus, 2017, 7, 1-11.
[189]
López, L.; Varea, O.; Navarro, S.; Carrodeguas, J.; Sanchez de Groot, N.; Ventura, S.; Sancho, J. Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation. Int. J. Mol. Sci., 2016, 17, 964.
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