Mechanisms of Action of Flavonoids in the Management of Diabetes mellitus

  • S Chandra Mohan Department of Chemistry, Sarvepalli Radhakrishnan University, NH-12, Hoshangabad Road, Jatkhedi, Bhopal- 462026, Madhya Pradesh
  • Namrata Jain Department of Chemistry, Sarvepalli Radhakrishnan University, NH-12, Hoshangabad Road, Jatkhedi, Bhopal- 462026, Madhya Pradesh, India.
  • S. Sumathi Department of Chemistry, Kunthavai Naacchyiaar Government Arts College for Women (Affiliated to Bharathidasan University), Thanjavur-613007, Tamil Nadu, India

Abstract

Management of diabetes mellitus is a challenge for clinicians. Uncontrolled hyperglycemia increases the risk of microvascular and macrovascular complications, damaging the body systems.  Although a number of antidiabetic drugs are available for therapeutic intervention, toxicity, loss of efficacy in chronic use and high cost of treatment have necessitated the search for new molecules to manage diabetes. Safety and cost are the main prerequisite for the new antidiabetic molecules. Medicinal plants and their purified phytochemicals have shown promising antidiabetic potential in the past few years. The flavonoids can be widely classified into different categories like anthocyanins, catechins, flavanols, flavones, flavanones etc. Some flavonoids have hypoglycemic properties. They may improve al-tered glucose and oxidative metabolisms of diabetic states. The hypoglycemic effect of some herbal extracts has been confirmed in human and animal models of type 2 diabetes mellitus (T2DM). Some of the important phytoconstituents from the classes of flavonoid have been discussed here. The current review summarizes the  antidiabetic activity of flavonoids, the mechanism-based action of flavonoids that target the various metabolic pathways in humans.


Keywords: Diabetes mellitus, Flavonoids, Medicinal plants, mechanisms of action, T2DM

Keywords: Diabetes mellitus, Flavonoids, Medicinal plants, mechanisms of action, T2DM

Downloads

Download data is not yet available.

Author Biographies

S Chandra Mohan, Department of Chemistry, Sarvepalli Radhakrishnan University, NH-12, Hoshangabad Road, Jatkhedi, Bhopal- 462026, Madhya Pradesh

Department of Chemistry,  Sarvepalli Radhakrishnan University, NH-12, Hoshangabad Road, Jatkhedi, Bhopal- 462026, Madhya Pradesh, India.

Namrata Jain, Department of Chemistry, Sarvepalli Radhakrishnan University, NH-12, Hoshangabad Road, Jatkhedi, Bhopal- 462026, Madhya Pradesh, India.

Department of Chemistry,  Sarvepalli Radhakrishnan University, NH-12, Hoshangabad Road, Jatkhedi, Bhopal- 462026, Madhya Pradesh, India.

S. Sumathi, Department of Chemistry, Kunthavai Naacchyiaar Government Arts College for Women (Affiliated to Bharathidasan University), Thanjavur-613007, Tamil Nadu, India

Department of Chemistry, Kunthavai Naacchyiaar Government Arts College for Women (Affiliated to Bharathidasan University), Thanjavur-613007, Tamil Nadu, India

References

1. Porth CM, Essentials of Pathophysiology: Concepts of Altered Health States, 3rd ed.; Wolters Kluwer: Alphenaan den Rijn, The Netherlands, 15 October 2010; Volume 3. ISBN-10 1582557241; ISBN-13 978-1582557243
2. Nogueira C, Souto SB, Vinha E, Braga DC, Carvalho D, Oral glucose lowering drugs in type 2 diabetic patients with chronic kidney disease, Hormones (Athens) 2013; 12:483-494. https://doi.org/10.14310/horm.2002.1436
3. Souto, SB, Souto EB, Braga DC, Medina JL, Prevention and current onset delay approaches of type 2 diabetes mellitus (T2DM), Eur J Clin Pharmacol, 2011; 67:653-661. https://doi.org/10.1007/s00228-011-1038-z
4. Vieira R, Souto SB, Sanchez-Lopez E, Machado AL, Severino P, Jose S, et. al., Sugar-Lowering Drugs for Type 2 Diabetes Mellitus and Metabolic Syndrome-Strategies for In Vivo Administration: Part-II, J Clin Med, 2019; 8:1332. https://doi.org/10.3390/jcm8091332
5. Ali MA, Wahed MI, Khatune NA, Rahman BM, Barman RK, Islam MR, Antidiabetic and antioxidant activities of ethanolic extract of Semecarpus anacardium (Linn.) bark, BMC Complement Altern Med, 2015; 15:138. https://doi.org/10.1186/s12906-015-0662-z
6. Bebernitz GR, Dain JG, Deems RO, Otero DA, Simpson WR, Strohschein RJ, Reduction in Glucose Levels in STZ Diabetic Rats by 4-(2,2-Dimethyl-1-oxopropyl)benzoic acid: AProdrugApproach for Targeting the Liver, J Med Chem, 2001; 44:512-523. https://doi.org/10.1021/jm000264w
7. Scheen AJ, Pharmacodynamics,Ecacy and Safety of Sodium-Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus, Drugs, 2015; 75:33-59. https://doi.org/10.1007/s40265-014-0337-y
8. Vivot K, Pasquier A, Goginashvili A, Ricci R, Breaking Bad and Breaking Good: Beta-Cell Autophagy Pathways in Diabetes, J Mol Biol, 2019. https://doi.org/10.1016/j.jmb.2019.07.030
9. Venkatesh S, Madhava Reddy B, Dayanand Reddy G, Mullangi R and Lakshman M, Antihyperglycemic and hypolipidemic effects of Helicteres isoraroots in alloxan-induced diabetic rats: A possible mechanism of action, J Nat Med, 2010; 64:295-304. https://doi.org/10.1007/s11418-010-0406-9
10. Pareek H, Sharma S, Khajja B S, Jain K and Jain G C, Evaluation of hypoglycemic and anti hyperglycemic potential of Tridax procumbens(Linn.), BMC Compl Altern Med, 2009; 9:48. https://doi.org/10.1186/1472-6882-9-48
11. Meenakshi P, Bhuvaneshwari R, Rathi M A, Thirumoorthi L, Guravaiah D C, Jiji M, et al., Antidiabetic activity of ethanolic extract of Zaleya decandrain alloxan-induced diabetic rat, Appl Biochem Biotechnol, 2010; 162:1153-1159. https://doi.org/10.1007/s12010-009-8871-x
12. Manach C, Scalbert A, Morand C, Remesy C and Jimenez L, Polyphenols: Food sources and bioavailability, Am J Clin Nutr, 2013; 79:727-747. https://doi.org/10.1093/ajcn/79.5.727
13. Xiao J, Kai G, Yamamoto K and Chen X, Advance in dietary polyphenols as alpha glucosidases inhibitors: A review on structure-activity relationship aspect, Crit Rev Food Sci Nutr, 2013; 53:818-836. https://doi.org/10.1080/10408398.2011.561379
14. Robertson S, What are flavonoids, New Med Life Sci Med, 2016, https://www.news-medical.net/health/what- are-Flavonoids-aspx.
15. Ramachandran V and Baojun X, Antidiabetic properties of dietary flavonoids: A cellular mechanism review, Nutr Metabol, 2015; 12:60. https://doi.org/10.1186/s12986-015-0057-7
16 Manuel Y, Keenoy B, Vertommen J and De Leeuw I, The effect of flavonoid treatment on the glycation and antioxidant status in type I diabetic patients, Diabetes Nutr Metabol, 1999; 12:256-63.
17. Campanero MA, Escolar M, Perez G, Garcia-Quetglas E, Sadaba B, et al., Simultaneous determination of diosmin and diosmetin in human plasma by ion trap liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry: Application to a clinical pharmacokinetic study, J Pharm Biomed Anal, 2010; 51:875-81. https://doi.org/10.1016/j.jpba.2009.09.012
18. Pari L and Srinivasan S, Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats, Biomed Pharmacother, 2010; 64:477-81. https://doi.org/10.1016/j.biopha.2010.02.001
19. Srinivasan S and Pari L. Antihyperlipidemic effect of diosmin: A citrus flavonoid on lipid metabolism in experimental diabetic rats, J Funct Foods, 2010; 5:484-92. https://doi.org/10.1016/j.jff.2012.12.004
20. Constantin RP, Constantin J, Pagadigorria CL, Ishii-Iwamoto EL, Bracht A, et al., The actions of fisetin on glucose metabolism in the rat liver, Cell Biochem Funct, 2010; 28:149-58. https://doi.org/10.1002/cbf.1635
21. Prasath GS, Pillai S and Subramanian SP, Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats, European J Pharmacol, 2014; 740:248-54. https://doi.org/10.1016/j.ejphar.2014.06.065
22. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, et al., Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration, J Nutr, 2000; 130:2243-2250. https://doi.org/10.1093/jn/130.9.2243
23. Kim MS, Hur HJ, Kwon DYand 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; 358:127-134. https://doi.org/10.1016/j.mce.2012.03.013
24. Sendrayaperumal V, Iyyam Pillai S and Subramanian S, Design, synthesis and characterization of zinc-morin, a metal flavonol complex and evaluation of its anti-diabetic potential in HFD-STZ induced type 2 diabetes in rats, Chem-Biol Interact, 2014; 219:9-17. https://doi.org/10.1016/j.cbi.2014.05.003
25. Abuohashish HM, Al-Rejaie SS, Al-Hosaini KA, Parmar MY and Ahmed MM, Alleviating effects of morin against experimentally-induced diabetic osteopenia, Diabetol Metab Syndr, 2013; 5:5. https://doi.org/10.1186/1758-5996-5-5
26. Wang X, Zhang DM, Gu TT, Ding XQ, Fan CY, et al.,Morin reduces hepatic inflammation-associated lipid accumulation in high fructose-fed rats via inhibiting sphingosine kinase 1/sphingosine 1-phosphate signaling pathway, Biochem Pharmacol, 2013; 86:1791-804. https://doi.org/10.1016/j.bcp.2013.10.005
27. Vanitha P, Uma C, Suganya N, Bhakkiyalakshmi E, Suriyanarayanan S, et al., Modulatory effects of morin on hyperglycemia by attenuating the hepatic key enzymes of arbohydrate metabolism and β-cell function in streptozotocin-induced diabetic rats, Environ Toxicol Pharmacol, 2014; 37:326-35. https://doi.org/10.1016/j.etap.2013.11.017
28. Sreedharan V, Venkatachalam KK and Namasivayam N, Effect of morin on tissue lipid peroxidation and antioxidant status in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis, Invest New Drugs, 2009; 27:21-30. https://doi.org/10.1007/s10637-008-9136-1
29. Ricardo KFS, Toledo de Oliveira T, Nagem TJ, Pinto AS, Oliveira MGA, et al.,Effect of flavonoids morin; quercetin and nicotinic acid on lipid metabolism of rats experimentally fed with triton, Brazillian Arch Biol Technol, 2001; 44:263-267. https://doi.org/10.1590/S1516-89132001000300007
30. Zhang WY, Lee JJ, Kim Y, Kim IS, Han JH, et al., Effect of eriodictyol on glucose uptake and insulin resistance in vitro , J Agric Food Chem, 2012; 60:7652-7658. https://doi.org/10.1021/jf300601z
31 Bucolo C, Leggio GM, Drago F and Salomone S, Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats, Biochem Pharmacol, 2012; 84: 88-92. https://doi.org/10.1016/j.bcp.2012.03.019
32. Miyake Y, Yamamoto K, Tsujihara N and Osawa T, Protective effects of lemon flavonoids on oxidative stress in diabetic rats, Lipids, 1998; 33:689-695. https://doi.org/10.1007/s11745-998-0258-y
33. Emim JA, Oliveira AB and Lapa AJ, Pharmacological evaluation of the anti-inflammatory activity of a citrus bioflavonoid, hesperidin, and the isoflavonoids, duartin and claussequinone, in rats and mice, J Pharm Pharmacol,1994; 46:118-122. https://doi.org/10.1111/j.2042-7158.1994.tb03753.x
34. Kawaguchi K, Mizuno T, Aida K and Uchino K, Hesperidin as an inhibitor of lipases from porcine pancreas and Pseudomonas, Biosci Biotechnol Biochem,1997; 61:102-104. https://doi.org/10.1271/bbb.61.102
35. Visnagri A, Kandhare AD, Chakravarty S, Ghosh P and Bodhankar SL, Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions, Pharm Biol, 2014; 52:814-828. https://doi.org/10.3109/13880209.2013.870584
36. Gumieniczek A, Effect of the new thiazolidinedione-pioglitazone on the development of oxidative stress in liver and kidney of diabetic rabbits, Life Sci, 2003; 74:553-562. https://doi.org/10.1016/j.lfs.2003.03.004
37. Shi X, Liao S, Mi H, Guo C, Qi D, et al., Hesperidin prevents retinal and plasma abnormalities in streptozotocin-induced diabetic rats, Molecules, 2012; 17:12868-12881. https://doi.org/10.3390/molecules171112868
38. Akiyama S, Katsumata S, Suzuki K, Ishimi Y, Wu J, et al.,Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats, J Clin Biochem Nutr, 2010; 46:87-92. https://doi.org/10.3164/jcbn.09-82
39. Yo A, Sharma P K, Shrivastava B, Ojha S, Upadhya HM, et al.,Hesperidin produces cardioprotective activity via PPAR-γ pathway in ischemic heart disease model in diabetic rats, PLoS One, 2014; 9:111-212. https://doi.org/10.1371/journal.pone.0111212
40. Wilcox LJ, Borradaile NM and Huff MW, Anti-atherogenic properties of naringenin, a citrus flavonoid, Cardiovasc Drug Rev,1999; 17:160-178. https://doi.org/10.1111/j.1527-3466.1999.tb00011.x
41. Sanchez-Salgado JC, Ortiz-Andrade RR, Aguirre-Crespo F, Vergara-Galicia J, Leon-Rivera I, et al, Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum vitifolium(willd.) sprengel: A potential agent for the treatment of metabolic syndrome, J Ethnopharmacol, 2007; 109:400-405. https://doi.org/10.1016/j.jep.2006.08.008
42. Priscilla DH, Roy D, Suresh A, Kumar V and Thirumurugan K, Naringenin inhibits α-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats, Chem-Biol Interac, 2014; 210:77-85. https://doi.org/10.1016/j.cbi.2013.12.014
43. Li JM, Che CT, Lau CBS, Leung PS and Cheng CHK, Inhibition of intestinal andrenal Na+-glucose co-transporter by naringenin, Int J Biochem Cell Biol, 2006; 38:985-995. https://doi.org/10.1016/j.biocel.2005.10.002
44. Pu P, Gao DM, Mohamed S, Chen J, Zhang J, et al.,Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet, Arch Biochem Biophys, 2012; 518:61-70. https://doi.org/10.1016/j.abb.2011.11.026
45. Zygmunt K, Faubert B, MacNeil J and Tsiani E, Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK, Biochem Biophys Res Commun, 2010; 398:178-183. https://doi.org/10.1016/j.bbrc.2010.06.048
46. Priscilla DH, Jayakumar M and Thirumurugan K, Flavanone naringenin: An effective antihyperglycemic and antihyperlipidemic nutraceutical agent on high fat diet fed streptozotocin induced type 2 diabetic rats, J Funct Foods, 2015; 14:363-373. https://doi.org/10.1016/j.jff.2015.02.005
47. Ross JA and Kasum CM, Dietary flavonoids: Bioavailability, metabolic effects, and safety, Annual Rev Nutr, 2002; 22:19-34. https://doi.org/10.1146/annurev.nutr.22.111401.144957
48. Hossain CM, Ghosh MK, Satapathy BS, Dey NS and Mukherjee B, Apigenin causes biochemical modulation, GLUT4 and Cd38 alterations to improve diabetes and to protect damages of some vital organs in experimental diabetes, Am J Pharmacol Toxicol, 9; 39-52. https://doi.org/10.3844/ajptsp.2014.39.52
49. Panda S and Kar A, Apigenin, 4',5,7-trihydroxyflavone regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice, J Pharm Pharmacol, 2007; 59:1543-1548. https://doi.org/10.1211/jpp.59.11.0012
50. Stavniichuk R, Drel VR, Shevalye H, Maksimchyk Y, Kuchmerovska TM, et al.,Baicalein alleviates diabetic peripheral neuropathy through inhibition of oxidative-nitrosative stress and p38 MAPK activation, Exp Neurol, 2011; 230:106-113. https://doi.org/10.1016/j.expneurol.2011.04.002
51. Ahad A, Mujeeb M, Ahsan H and Siddiqui WA, Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats, Biochem, 2014; 106:101-110. https://doi.org/10.1016/j.biochi.2014.08.006
52. Kim YO, Leem K, Park J, Lee P, Ahn DK, et al., Cytoprotective effect ofScutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia, J Ethnopharmacol, 2001; 77:183-88. https://doi.org/10.1016/S0378-8741(01)00283-5
53. Lapchak PA, Maher P, Schubert D and Zivin J A, Baicalein, an antioxidant12/15-lipoxygenase inhibitor improves clinical rating scores following multiple infarct embolic strokes, Neurosci, 2007; 150:585-591. https://doi.org/10.1016/j.neuroscience.2007.09.033
54. Siess MH, LeBon AM, Canivenc-Laver MC, Amiot MJ, Sabatier S, et al.,Flavonoids of honey and propolis: Characterization and effects on hepatic drug-metabolising enzymes and benz[a]pyr ene-DNA binding in rats, J Agric Food Chem,1996; 44:2379-2383. https://doi.org/10.1021/jf9504733
55. Dhawan K, Kumar S and Sharma A, Beneficial effects of chrysin and benzoflavone on virility in 2-year-old male rats, J Med Food, 2002; 5:43-48. https://doi.org/10.1089/109662002753723214
56. Sandborn WJ and Faubion WA, Clinical pharmacology of inflammatory bowel disease therapies, Curr Gastroenterol Rep, 2000; 2:440-445. https://doi.org/10.1007/s11894-000-0005-0
57. Sirovina D, Orsolić N, Koncić MZ, Kovacević G, Benković V, et al, Quercetin vs chrysin: Effect on liver histopathology in diabetic mice, Human Exp Toxicol, 2013; 32:1058-1066. https://doi.org/10.1177/0960327112472993
58. Ding L, Jin D and Chen X, Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes, J Nutr Biochem, 2010; 21:941-947. https://doi.org/10.1016/j.jnutbio.2009.07.009
59. Liu Y, Fu X, Lan N, Li S, Zhang J, et al.,Luteolin protects against high fat diet-induced cognitive deficits in obesity mice, Behav Brain Res, 2014 ; 267:178-188. https://doi.org/10.1016/j.bbr.2014.02.040
60. Ding Y, Shi X, Shuai X, Xu Y, Liu Y, et al.,Luteolin prevents uric acid-induced pancreatic β-cell dysfunction, J Biomed Res, 2014; 28:292-298.
61. Neuhouser ML, Dietary flavonoids and cancer risk: Evidence from human population studies, Nutr Cancer, 2004; 50:1-7. https://doi.org/10.1207/s15327914nc5001_1
62. Miean KH and Mohamed S, Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants, J Agric Food Chem, 2001; 49:3106-3112. https://doi.org/10.1021/jf000892m
63. Gates MA, Tworoger SS, Hecht JL, De Vivo I, Rosner B, et al.,A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer, Int J Cancer, 2007; 12: 2225-2232. https://doi.org/10.1002/ijc.22790
64. Kim MS, Hur HJ, Kwon DY and 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; 358:127-134. https://doi.org/10.1016/j.mce.2012.03.013
65. Ku SK and Bae JS, Baicalin, baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitroand in vivo, BMB Rep, 2015; 48:519-524. https://doi.org/10.5483/BMBRep.2015.48.9.017
66. Tai MC, Tsang SY, Chang LY and Xue H, Therapeutic potential of wogonin: A naturally occurring flavonoid, CNS Drug Rev, 2005; 11:141-150. https://doi.org/10.1111/j.1527-3458.2005.tb00266.x
67. Bak EJ, Kim J, Choi YH, Kim JH, Lee DE, et al.,Wogonin ameliorates hyperglycemia and dyslipidemia via PPARα activation in db/db mice, Clin Nutr, 2014; 33:156-163. https://doi.org/10.1016/j.clnu.2013.03.013
68. Yokozawa T, Kim HY, Cho EJ, Choi JS and Chung HY, Antioxidant effects of isorhamnetin 3,7-di-O-beta-D-glucopyranoside isolated from mustard leaf (Brassica juncea) in rats with streptozotocin-induced diabetes, J Agric Food Chem, 2002; 50:5490-495. https://doi.org/10.1021/jf0202133
69. Lee YS, Lee S, Lee HS, Kim BK, Ohuchi K, et al., Inhibitory effects of isorhamnetin-3-O-beta-D-glucoside fromSalicornia herbacea on rat lens aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues, Biol Pharm Bullet, 2005; 28:916-918. https://doi.org/10.1248/bpb.28.916
70. Rodríguez-Rodríguez C, Torres N, Gutiérrez-Uribe JA, Noriega LG, Torre-Villalvazo I, et al.,The effect of isorhamnetin glycosides extracted from Opuntia ficus indica in a mouse model of diet induced obesity, Food Funct, 2015; 6:805-815. https://doi.org/10.1039/C4FO01092B
71. An G, Gallegos J and Morris ME, The bioflavonoid kaempferol is an abcg2 substrate and inhibits abcg2-mediated quercetin efflux, Drug Metab Dispos, 2011; 39:426-432. https://doi.org/10.1124/dmd.110.035212
72. Hakkinen SH, Karenlampi SO, Heinonen IM, Mykkanen HM and Torronen AR, Content of the flavonols quercetin, myricetin, and kaempferolin 25 edible berries, J Agric Food Chem, 1999; 47:2274-2279. https://doi.org/10.1021/jf9811065
73. Nirmala P and Ramanathan M, Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal carcinoma in rats, Eur J Pharm, 2011; 654:75-79. https://doi.org/10.1016/j.ejphar.2010.11.034
74. Zhang Y and Liu D, Flavonol kaempferol improves chronic hyperglycemia-impaired pancreatic beta-cell viability and insulin secretory function, Eur J Pharmacol, 2011; 670:325-332. https://doi.org/10.1016/j.ejphar.2011.08.011
75. Al-Numair KS, Chandramohan G, Veeramani C and Alsaif MA, Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats, Redox Rep, 2015; 20:198-209. https://doi.org/10.1179/1351000214Y.0000000117
76. Abo-Salem OM, Kaempferol attenuates the development of diabetic neuropathic pain in mice: Possible anti-inflammatory and anti-oxidant mechanisms, Maced J Med Sci, 2014; 7:424-430. https://doi.org/10.3889/oamjms.2014.073
77. Kreft S, Knapp M and Kreft I, Extraction of rutin from buckwheat (Fagopyrum esculentumMoench) seeds and determination by capillary electrophoresis, J Agric Food Chem,1999; 47:4649-4652. https://doi.org/10.1021/jf990186p
78. Huang WY, Zhang HC, Liu WX and Li CY, Survey of antioxidant capacity and phenolic composition of blueberry, blackberry and strawberry in Nanjing, J Zhe Univ Sci B, 2012; 13:94-102. https://doi.org/10.1631/jzus.B1100137
79. Ghorbani A, Mechanisms of antidiabetic effects of flavonoid rutin, Biomedicine & Pharmacotherapy, 2017; 96:305-312. https://doi.org/10.1016/j.biopha.2017.10.001
80. Niture NT, Ansari AA and 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; 52:720-727.
81. Hollman PCH, de Vries JHM, van Leeuwen SD, Mengelers MJB and Katan MB, Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers, Am J Clin Nutr, 1995; 62:1276-1282. https://doi.org/10.1093/ajcn/62.6.1276
82. Alinezhad H, Azimi A, Zare M, Ebrahimzadeh MA, Eslami S, et al.,Antioxidant and antihemolytic activities of ethanolic extract of flowers, leaves, and stems ofHyssopus officinalis L. var. angustifolius, Int J Food Prop, 2013; 16:1169-1178. https://doi.org/10.1080/10942912.2011.578319
83. Coskun O, Kanter M, Korkmaz A and Oter S, Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas, Pharmacol Res, 2005; 51:117-123. https://doi.org/10.1016/j.phrs.2004.06.002
84. Stewart LK, Wang Z, Ribnicky D, Soileau J L, Cefalu WT, et al.,Failure of dietary quercetin to alter the temporal progression of insulin resistance among tissues of C57BL/6 J mice during the development of diet-induced obesity, Diabetologia, 2009; 52:514-523. https://doi.org/10.1007/s00125-008-1252-0
85. Kobori M, Masumoto S, Akimoto Y and Takahashi Y, Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice, Mol Nutr Food Res, 2009; 53:859-868. https://doi.org/10.1002/mnfr.200800310
86. Patisaul HB and Jefferson W, The pros and cons of phytoestrogens, Front Neuroendocrinol, 2010; 31:400-419. https://doi.org/10.1016/j.yfrne.2010.03.003
87. Elmarakby AA, Ibrahim AS, Faulkner J, Mozaffari MS, Liou GI, et al.,Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin induced diabetic mice, Vascul Pharmacol, 2011; 55:149-156. https://doi.org/10.1016/j.vph.2011.07.007
88. Kapiotis S, Jilma B and Szalay Y, Evidence against an effect of endothelin-1 on blood coagulation, fibrinolysis, and endothelial cell integrity in healthy men, Arterioscler Thromb Vasc Biol, 1997; 17:2861-2867. https://doi.org/10.1161/01.ATV.17.11.2861
89. Park SA, Choi MS, Cho SY, Seo JS, Jung UJ, et al., Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/Ks J-db/db mice, Life Sci, 2006; 79:1207-1213. https://doi.org/10.1016/j.lfs.2006.03.022
90. Cederroth CR, Vinciguerra M, Gjinovci A, Kuhne F, Klein M, et al., Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism, Diabetes, 2008; 57:1176-1185. https://doi.org/10.2337/db07-0630
91. Cheong SH, Furuhashi K, Ito K, Nagaoka M, Yonezawa T, et al., Daidzein promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and improves glucose homeostasis in type II diabetic model mice, J Nutr Biochem, 2014; 25:136-143. https://doi.org/10.1016/j.jnutbio.2013.09.012
92. Akkarachiyasit S, Charoenlertkul P, Yibchok-Anun S and Adisakwattana S, Inhibitory activities of cyanidin and its glycosides and synergistic effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase, Int J Mol Sci, 2010; 11:3387-3396. https://doi.org/10.3390/ijms11093387
93. Nasri S, Roghani M, Baluchnejadmojarad T, Rabani T and Balvardi M, Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats, Pathophysiol, 2011; 18:273-278. https://doi.org/10.1016/j.pathophys.2011.03.001
94. Zhu W, Jia Q, Wang Y, Zhang Y and Xia M, The anthocyanin cyanidin-3-O-betaglucoside, a flavonoid, increases hepatic glutathione synthesis and protects hepatocytes against reactive oxygen species during hyperglycemia: Involvement of a cAMP-PKA-dependent signaling pathway, Free Rad Biol Med, 2012; 52:314-327. https://doi.org/10.1016/j.freeradbiomed.2011.10.483
95. Gharib A, Faezizadeh Z and Godarzee M, Treatment of diabetes in the mouse model by delphinidin and cyanidin hydrochloride in free and liposomal forms, Planta Medica, 2013; 79:1599-1604 https://doi.org/10.1055/s-0033-1350908
96. Mazza G, Compositional and functional properties of saskatoon berry and blueberry, Int J Fruit Sci , 2005; 5:101. https://doi.org/10.1300/J492v05n03_10
97. Mirshekar, M.; Roghani, M.; Khalili, M.; Baluchnejadmojarad, T. Chronic oral pelargonidin alleviates learning and memory disturbances in streptozotocin diabetic rats. Iran J Pharm Res, 2011; 10:569-575.
98. Mirshekar M, Roghani M, Khalili M, Baluchnejadmojarad T and Arab M S, Chronic oral pelargonidin alleviates streptozotocin-induced diabetic neuropathic hyperalgesia in rat: Involvement of oxidative stres, Iranian Biomed J, 2010; 14:33-39.
99. Roman-Ramos R, Flores-Saenz JL and Alarcon-Aguilar FL, Anti-hyperglycemic effect of some edible plants, J Ethnopharmacol, 1995; 48: 25-32. https://doi.org/10.1016/0378-8741(95)01279-M
100. Hii SCT and Howell SL, Effects of epicatechin on rat islets of Langerhans, Diabetes 1984; 33: 291-296. https://doi.org/10.2337/diabetes.33.3.291
101. Waltner-Law ME, Wang XL, Law BK, Epigallocatechin gallate: a constituent of green tea, represses hepatic glucose production, J Biol Chem, 2002; 277: 34933-34940. https://doi.org/10.1074/jbc.M204672200
102. Vessal M, Hemmati M and Vasei M, Hypoglycemic effects of quercetin in streptozocin-induced diabetic rats: comparative biochemistry and physiology, Toxicol Pharmacol, 2003; 135:357-364. https://doi.org/10.1016/S1532-0456(03)00140-6
103. Ngueyem TA, Brusotti G, Caccialanza G, The genus Bridelia: a phytochemical and ethnopharmacological review, J Ethnopharmacol, 2009; 124: 339-349. https://doi.org/10.1016/j.jep.2009.05.019
104. Jung UJ, Lee MK, Jeong KS, The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice, J Nutr, 2004; 134:2499-2503. https://doi.org/10.1093/jn/134.10.2499
105. Liu KZ, Li JB, Lu HL, Effects of Asiragalus and saponins of Panax notoginseng on MMP-9 in patients with type 2 diabetic, Macroangiopathy, 2004; 29:264-266.
106. Jellin JM, Batz F and Hitchens K, Pharmacist's letter/prescriber's letter natural medicines comprehensive database. Stockton, CA: Therapeutic Research Faculty, 1999.
107. Howes JB, Tran D, Brillante D, Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes. Diabetes Obes Metab, 2003; 5:325-332. https://doi.org/10.1046/j.1463-1326.2003.00282.x
108. Mezei O, Banz WJ, Steger RW, Soy isoflavones exert hypoglycemic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells, J Nutr, 2003; 133:1238-1243. https://doi.org/10.1093/jn/133.5.1238
109. Gray AM and Flatt PR, Insulin-releasing and insulin-like activity of Agaricus campestris (mushroom), J Endocrinol, 1998; 157:259-266. https://doi.org/10.1677/joe.0.1570259
110. Pinent M, Blay M, Blade MC, Grape seed-derived procyanidins have an antihyperglycemic effect in streptozotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines, Endocrinology, 2004; 145:4985-4990. https://doi.org/10.1210/en.2004-0764
111. Jorge AP, Horst H, de Sousa E, et al, Insulinomimetic effects of kaempferitrin on glycaemia and on glucose uptake in rat soleus muscle, Chem Biol Interact, 2004; 149: 89-96. https://doi.org/10.1016/j.cbi.2004.07.001
112. Van de Venter M, Roux S, Bungu LC, Antidiabetic screening and scoring of 11 plants traditionally used in South Africa, J Ethnopharmacol, 2008; 119: 81-86. https://doi.org/10.1016/j.jep.2008.05.031
113. Huseini HF, Larijani B, Heshmat R, The efficacy of Silybum marianum(L.) Gaertn (Silymarin) in the treatment of type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res, 2006; 20:1036-1039. https://doi.org/10.1002/ptr.1988
114. Cooper EJ, Hudson AL, Parker CA, Effects of the beta-carbolines, harmane and pinoline, on insulin secretion from isolated human islets of Langerhans, Eur J Pharmacol, 2003; 482:189-196. https://doi.org/10.1016/j.ejphar.2003.09.039
115. Kirtikar KR and Basu BD, Indian medicinal plants, vol 1, 1998.
116. Prakasam A, Sethupathy S and Pugalendia KV. Antiperoxidative and antioxidant effects of Casearia esculentaroot extract in streptozotocin induced diabetic rats, Yale J Biol Med, 2005; 78:15-23.
117. Shane-McWhorter L, Biological complementary therapies: a focus on botanical products in diabetes, Diabetes Spectr, 2001; 14:199-208. https://doi.org/10.2337/diaspect.14.4.199
118. Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, Busselberg D, Flavonoids in Cancer and Apoptosis. Cancers (Basel), 2018; 11:28. https://doi.org/10.3390/cancers11010028
119. AL-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D, Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels, Biomolecules. 2019; 9:430. https://doi.org/10.3390/biom9090430
Crossmark
Statistics
688 Views | 56 Downloads
How to Cite
1.
Chandra Mohan S, Jain N, Sumathi S. Mechanisms of Action of Flavonoids in the Management of Diabetes mellitus. JDDT [Internet]. 15Oct.2021 [cited 17May2024];11(5-S):194-02. Available from: https://jddtonline.info/index.php/jddt/article/view/5101