Welcome to Francis Academic Press
Login | Register

Academic Journal of Medicine & Health Sciences, 2024, 5(2); doi: 10.25236/AJMHS.2024.050203.

Research progress of isoquercitrin in the treatment of diabetes and its complications

Author(s)

Sihua Lu1, Guihong Huang2,3,4,5

Corresponding Author:
Guihong Huang
Affiliation(s)

1Lingui Clinical College, Guilin Medical University, Guilin, Guangxi, 541199, China

2Department of Pharmacy, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541199, China

3Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, Key Laboratory of Diabetic Systems Medicine, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Guilin, Guangxi, 541199, China

4Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin, Guangxi, 541199, China

5Guangxi Clinical Research Center for Diabetes and Metabolic Diseases, Guilin, Guangxi, 541199, China

Abstract

Diabetes mellitus (DM) is a group of multifactorial metabolic disorders characterized by chronic high blood glucose levels. It is often the result of impaired insulin secretion or insulin resistance.This article discusses the improvement of isoquercitrin on diabetes and its associated complications, including type 2 diabetes, hepatic gluconeogenesis, and diabetic neuropathy. We reviewed the published related papers in detail, analyzed the pathogenesis of diabetes from the perspective of its pathogenesis, and showed how isoquercitrin affects its key signaling pathways by regulating the levels of related factors, and ultimately improves the role of diabetes and its related complications.

Keywords

Diabetes; Isoquercetrin; Complications of diabetes; Oxidative stress; Liver gluconeogenesis

Cite This Paper

Sihua Lu, Guihong Huang. Research progress of isoquercitrin in the treatment of diabetes and its complications. Academic Journal of Medicine & Health Sciences (2024), Vol. 5, Issue 2: 15-21. https://doi.org/10.25236/AJMHS.2024.050203.

References

[1] Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbanya JC, Pavkov ME, Ramachandaran A, Wild SH, James S, Herman WH, Zhang P, Bommer C, Kuo S, Boyko EJ, Magliano DJ. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022 Jan; 183:109119. doi: 10.1016/j.diabres.2021.109119. Epub 2021 Dec 6. Erratum in: Diabetes Res Clin Pract. 2023 Oct;204:110945. PMID: 34879977.

[2] Ong KC, Khoo HE. Effects of myricetin on glycemia and glycogen metabolism in diabetic rats. Life Sci. 2000 Aug 25;67(14):1695-705. doi: 10.1016/s0024-3205(00)00758-x. PMID: 11021354.

[3] Kao YH, Hiipakka RA, Liao S. Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology. 2000 Mar;141(3):980-7. doi: 10.1210/endo.141.3.7368. PMID: 10698173.

[4] Tsuneki H, Ishizuka M, Terasawa M, Wu JB, Sasaoka T, Kimura I. Effect of green tea on blood glucose levels and serum proteomic patterns in diabetic (db/db) mice and on glucose metabolism in healthy humans. BMC Pharmacol. 2004 Aug 26;4:18. doi: 10.1186/1471-2210-4-18. PMID: 15331020; PMCID: PMC517497.

[5] Sabu MC, Smitha K, Kuttan R. Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes. J Ethnopharmacol. 2002 Nov;83(1-2):109-16. doi: 10.1016/s0378-8741(02)00217-9. PMID: 12413715.

[6] Song, J., Kwon, O., Chen, S., Daruwala, R., Eck, P., Park, J. B., and Levine, M. Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and glucose. J. Biol. Chem. 2002, 277, 15252–15260.

[7] Douglass, C.D., Howard, W.L., Wender, S.H., 1949. The isolation of isoquercitrin from the seed pods of Cercis canadensis. J. Am. Chem. Soc. 71, 2658–2659.

[8] Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005 Apr 9-15;365(9467):1333-1346. doi: 10.1016/S0140-6736(05)61032-X. PMID: 15823385.

[9] Zhang R, Yao Y, Wang Y, Ren G. Antidiabetic activity of isoquercetin in diabetic KK - Ay mice. Nutr Metab (Lond). 2011 Dec 2;8:85. 

[10] Li YQ, Zhou FC, Gao F, Bian JS, Shan F. Comparative evaluation of quercetin, isoquercetin and rutin as inhibitors of alpha-glucosidase. J Agric Food Chem. 2009 Dec 23;57(24):11463-11468. doi: 10.1021/jf903083h. PMID: 19938837.

[11] Arango NA, Szotek PP, Manganaro TF, Oliva E, Donahoe PK, Teixeira J.2005. Conditional deletion of [beta]‐catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium. Dev Biol 288: 276–283.

[12] Resham K, Khare P, Bishnoi M, Sharma SS. Neuroprotective effects of isoquercitrin in diabetic neuropathy via Wnt/β-catenin signaling pathway inhibition. Biofactors. 2020 May;46(3):411-420.

[13] D. Wu, A.I. Cederbaum, Alcohol, oxidative stress, and free radical damage, Alcohol Res. Health (December (27)) (2003) 277–284.

[14] H. Bartsch, J. Nair, Oxidative stress and lipid peroxidation-derived DNA-lesions in inflammation driven carcinogenesis, Cancer Detect. Prev. 28 (December (6)) (2004)385–391.

[15] J.R. Speakman, C. Selman, The free‐radical damage theory: accumulating evidence against a simple link of oxidative stress to ageing and lifespan, Bioessays 33 (April(4)) (2011) 255–259.

[16] F. Giacco, M. Brownlee, Oxidative stress and diabetic complications, Circ. Res. 107(October (9)) (2010) 1058–1070.

[17] J.L. Evans, I.D. Goldfine, B.A. Maddux, G.M. Grodsky, Are oxidative stress− activated signaling pathways mediators of insulin resistance and β-cell dysfunction? Diabetes 52 (January (1)) (2003) 1–8.

[18] Devos, D.; Moreau, C.; Devedjian, J.C.; Kluza, J.; Petrault, M.; Laloux, C.; Jonneaux, A.; Ryckewaert, G.;Garçon, G.; Rouaix, N.; et al. Targeting chelatable Iron as a therapeutic modality in Parkinson’s disease.Antioxid. Redox Signal. 2014, 21, 195–210.

[19] Li X, Jiang Q, Wang T, Liu J, Chen D. Comparison of the Antioxidant Effects of Quercitrin and Isoquercitrin: Understanding the Role of the 6″-OH Group. Molecules. 2016 Sep 19;21(9):1246.

[20] Jayachandran M, Wu Z, Ganesan K, Khalid S, Chung SM, Xu B. Isoquercetin upregulates antioxidant genes, suppresses inflammatory cytokines and regulates AMPK pathway in streptozotocin -induced diabetic rats. Chem Biol Interact. 2019 Apr 25;303:62-69. 

[21] J.A. David, W.J. Rifkin, P.S. Rabbani, D.J. Ceradini, The Nrf2/Keap1/ARE pathway and oxidative stress as a therapeutic target in type II diabetes mellitus. J. Diab. Res.4826724 (2017) 1–15.

[22] COPPACK, S.W. 2001. Pro-inflammatory cytokines and adipose tissue. Proc. Nutr.Soc. 60: 349–356.

[23] Fève B, Bastard JP. The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol. 2009 Jun;5(6):305-311. doi: 10.1038/nrendo.2009.62. PMID: 19399017. 

[24] Hotamisligil GS. Mechanisms of TNF-alpha-induced insulin resistance. Exp Clin Endocrinol Diabetes. 1999;107(2):119-125. doi: 10.1055/s-0029-1212086. PMID: 10320052.

[25] Stephens JM, Pekala PH. Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. Regulations is coordinate and independent of protein synthesis. J Biol Chem. 1992 Jul 5;267(19):13580-13584. PMID: 1618860.

[26] STERN, M.P. 1995. Diabetes and cardiovascular disease. The “common soil” hypothesis. Diabetes 44: 369–374.

[27] Morikawa K, Nonaka M, Narahara M, Torii I, Kawaguchi K, Yoshikawa T, Kumazawa Y, Morikawa S. Inhibitory effect of quercetin on carrageenan-induced inflammation in rats. Life Sci. 2003 Dec 26;74(6):709-721. doi: 10.1016/j.lfs.2003.06.036. PMID: 14654164.

[28] Radziuk J. Tracer studies of liver metabolism. Horm Metab Res Suppl. 1990;24:31-40. PMID: 2272624.

[29] Bonner C,Kerr-Conte J,Gmyr V,et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion[J]. Nat Med,2015,21( 5) : 512-517.

[30] WEI S, LI W, YU Y, et al. Ginsenoside compound K suppresses the hepatic gluconeogenesis via activating adenosine-5'monophosphate kinase: A study in vitro and in vivo [J]. Life Sci, 2015(139): 8-15.

[31] Xie Xiuying, Chen Lin, Lei Tao, Lu Ming, Shen Tian, Xu Bilin. The effects of two components in the alcohol extract of okra on gluconeogenesis and AMPK in liver cells α Effect of phosphorylation [J].Traditional Chinese patent medicines and simple preparations, 2018,40 (05): 1167-1170.

[32] Chen Lin, Lu Ming, Shen Tian, Xie Xiuying, Xu Bilin, Lei Tao. Research on the effect of isoquercitrin on hepatocyte gluconeogenesis by regulating AMPK-TORC2 phosphorylation [J]. Chinese Journal of Diabetes, 2019,27 (01): 62-68.

[33] MONTMINY M, KOO S H, ZHANG X. The CREB family: key regulators of hepatic metabolism [J]. Ann Endocrinol(Paris), 2004, 65(1): 73-75.

[34] Yoon S,Lee W,Ryu D,et a1. Suppressor of MEK null(SMEK),proteinphosphatase 4 catalytic subunit(PP4C)is a key regulator of hepatic gluconeogenesis.Proc Nad Acad Sci USA, 2010, 107:17704-17709.

[35] Wang Fei The effect of metformin on AMPK and PPARs activity in the liver of high-fat fed rats - a possible mechanism for improving fatty liver [D] Jinan: Shandong University, 2008.

[36] XIE M, ZHANG D, DYCK J R, et al. Apivotal role for endogenous TGF-β-activated kinase-1 in the LKB1/AMPactivated protein kinase energy-sensor pathway [J]. PNAS, 2006, 1039(46): 17378-17383.

[37] Chen L, Shen T, Zhang CP, Xu BL, Qiu YY, Xie XY, Wang Q, Lei T. Quercetin and Isoquercitrin Inhibiting Hepatic Gluconeogenesis Through LKB1-AMPKα Pathway. Acta Endocrinol (Buchar). 2020 Jan-Mar; 16(1):9-14. 

[38] Zilliox L, Peltier AC, Wren PA, et al. Assessing autonomic dysfunction in early diabetic neuropathy: The survey of autonomic symptoms. Neurology. 2011;76:1099–1105.

[39] Sloan G, Shillo P, Selvarajah D, et al. A new look at painful diabetic neuropathy. Diabetes Res Clin Pract. 2018;144:177–191.

[40] Chen L, Feng P, Peng A, Qiu X, Lai W, Zhang L, Li W. Protective effects of isoquercitrin on streptozotocin-induced neurotoxicity. J Cell Mol Med. 2020 Sep;24(18):10458-10467.

[41] Ji RR, Xu ZZ, Gao YJ. Emerging targets in neuroinflammationdriven chronic pain. Nat Rev Drug Discov. 2014;13:533–548.

[42] Resham K, Khare P, Bishnoi M, Sharma SS. Neuroprotective effects of isoquercitrin in diabetic neuropathy via Wnt/β-catenin signaling pathway inhibition. Biofactors. 2020 May;46(3):411-420.

[43] Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003 Aug;125(2):437-443. doi: 10.1016/s0016-5085(03)00907-7. PMID: 12891546.

[44] Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism. 2016 Aug;65(8):1096-1108. doi: 10.1016/j.metabol.2016.01.001. Epub 2016 Jan 11. PMID: 26856933; PMCID: PMC4943559.

[45] Valenti L, Bugianesi E, Pajvani U, Targher G. Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes? Liver Int. 2016 Nov;36(11):1563-1579. doi: 10.1111/liv.13185. Epub 2016 Jun 30. PMID: 27276701.

[46] Villarreal-Garza, C.; Shaw-Dulin, R.; Lara-Medina, F.; Bacon, L.; Rivera, D.; Urzua, L.; Aguila, C.; Ramirez-Morales, R.; Santamaria,J.; Bargallo, E. Impact of diabetes and hyperglycemia on survival in advanced breast cancer patients. Exp. Diabetes Res. 2012, 2012,732027.

[47] Srivastava, S.P.; Goodwin, J.E. Cancer biology and prevention in diabetes. Cells 2020, 9, 1380.

[48] Ferroni P, Riondino S, Buonomo O, Palmirotta R, Guadagni F, Roselli M. Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress. Oxid Med Cell Longev. 2015;2015:183928. doi: 10.1155/2015/183928. Epub 2015 Jun 11. PMID: 26171112; PMCID: PMC4480937.

[49] Shui L, Wang W, Xie M, Ye B, Li X, Liu Y, Zheng M. Isoquercitrin induces apoptosis and autophagy in hepatocellular carcinoma cells via AMPK/mTOR/p70S6K signaling pathway. Aging (Albany NY). 2020 Nov 29;12(23):24318-24332.

[50] Won YS, Kim JH, Lizardo RCM, Min HJ, Cho HD, Hong SM, Seo KI. The Flavonol Isoquercitrin Promotes Mitochondrial-Dependent Apoptosis in SK-Mel-2 Melanoma Cell via the PI3K/AKT/mTOR Pathway. Nutrients. 2020 Nov 29;12(12):3683.

[51] Zwicker JI, Schlechter BL, Stopa JD, Liebman HA, Aggarwal A, Puligandla M, Caughey T, Bauer KA, Kuemmerle N, Wong E, Wun T, McLaughlin M, Hidalgo M, Neuberg D, Furie B, Flaumenhaft R; CATIQ Investigators11. Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer. JCI Insight. 2019 Feb 21; 4(4):e125851.