Trans-chalcone enhances insulin sensitivity through the miR-34a/SIRT1 pathway

Document Type : Original Article

Authors

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objective(s): Trans-chalcone as the parent member of the chalcone series reduces circulating levels of insulin and glucose. However, the cellular mechanism of these effects is poorly understood. Sirtuin 1 (SIRT1) as a direct target of miR-34a controls homeostasis of glucose, and also improves insulin sensitivity. Therefore, the present study for the first time investigated the influence of trans-chalcone on the miR-34a/SIRT1 pathway as a possible mechanism for its hypoglycemic and hypoinsulinemic effects.
Materials and Methods: In this study, thirty male rats were randomly divided into three groups (n=10): solvent control (NS), oral administration of trans-chalcone for 2 (N2T) and 6 weeks (N6T) groups. Then, hepatic levels of miR-34a and SIRT1 were measured through the qRT-PCR method.
Results: Trans-chalcone reduced food intake, body weight gain, and serum glucose as well as insulin levels. Also, this chalcone inhibited hepatic miR-34a expression and significantly elevated SIRT1 mRNA level.
Conclusion: Trans-chalcone as an insulin-sensitizing chalcone partly acts through the miR-34a/SIRT1 pathway.

Keywords

Main Subjects


1. Matos MJ, Vazquez-Rodriguez S, Uriarte E, Santana L. Potential pharmacological uses of chalcones: a patent review (from June 2011 – 2014). Expert Opin Ther Pat 2015; 25:351-366.
2. Orlikova B, Tasdemir D, Golais F, Dicato M, Diederich M. Dietary chalcones with chemopreventive and chemotherapeutic potential. Genes Nutr 2011; 6:125-147.
3. Singh H, Sidhu S, Chopra K, Khan M. Hepatoprotective effect of trans-chalcone on experimentally induced hepatic injury in rats: inhibition of hepatic inflammation and fibrosis. Can J Physiol Pharma 2016; 94:879-887.
4. Jalalvand F, Amoli MM, Yaghmaei P, Kimiagar M, Ebrahim-Habibi A. Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice. Arch Endocrinol Metab 2015; 59:202-209.
5. Batovska DI, Todorova IT. Trends in utilization of the pharmacological potential of chalcones. Curr Clin Pharmacol 2010; 5:1-29.
6. Aksöz BE, Ertan R. Chemical and Structural Properties of Chalcones I. FABAD J Pharm Sci 2011; 36:223-242.
7. Rahman MA. Chalcone: A valuable insight into the recent advances and potential pharmacological activities. Chem Sci J 2011; 2011:CSJ-29.
8. Yaghmaei P, Kheirbakhsh R, Dezfulian M, Haeri-Rohani A, Larijani B, Ebrahim-Habibi A. Indole and trans-chalcone attenuate amyloid β plaque accumulation in male Wistar rat: in vivo effectiveness of two anti-amyloid scaffolds. Arch Ital Biol 2013; 151:106-113.
9. Najafian M, Ebrahim-Habibi A, Yaghmaei P, Parivar K, Larijani B. Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: an in vivo study in rats. Acta Biochim Pol 2010; 57:553-560.
10. Liang F, Kume S, Koya D. SIRT1 and insulin resistance. Nat Rev Endocrinol 2009; 5:367-373.
11. Chen YR, Fang SR, Fu YC, Zhou XH, Xu MY, Xu WC. Calorie restriction on insulin resistance and expression of SIRT1 and SIRT4 in rats. Biochem Cell Biol 2010; 88:715-722.
12. Chakraborty C, Doss CG, Bandyopadhyay S, Agoramoorthy G. Influence of miRNA in insulin signaling pathway and insulin resistance: micro-molecules with a major role in type-2 diabetes. Wiley Interdiscip Rev RNA 2014; 5:697-712.
13. Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, et al. Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell 2013; 12:1062-1072.
14. Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, et al. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab 2007; 6:307-319.
15. Guarente L. Sirtuins, aging, and metabolism. Cold Spring Harb Symp Quant Biol 2011; 76:81-90.
16. Castro RE, Ferreira DM, Afonso MB, Borralho PM, Machado MV, Cortez-Pinto H, et al. MiR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol 2013; 58:119-125.
17. Guarente L. Sirtuins as potential targets for metabolic syndrome. Nature 2006; 444:868-874.
18. Klover PJ, Mooney RA. Hepatocytes: critical for glucose homeostasis. Int J Biochem Cell B 2004; 36:753-758.
19. Yang YM, Seo SY, Kim TH, Kim SG. Decrease of microRNA-122 causes hepatic insulin resistance by inducing protein tyrosine phosphatase 1B, which is reversed by licorice flavonoid. Hepatology 2012; 56:2209-2220.
20. Baselga-Escudero L, Arola-Arnal A, Pascual-Serrano A, Ribas-Latre A, Casanova E, Salvado MJ, et al. Chronic administration of proanthocyanidins or docosahexaenoic acid reverses the increase of miR-33a and miR-122 in dyslipidemic obese rats. PLoS One 2013; 8:e69817.
21. Baselga‐Escudero L, Bladé C, Ribas‐Latre A, Casanova E, Salvadó MJ, Arola L, et al. Grape seed proanthocyanidins repress the hepatic lipid regulators miR‐33 and miR‐122 in rats. Mol Nutr Food Res 2012; 56:1636-1646.
22. Baselga-Escudero L, Pascual-Serrano A, Ribas-Latre A, Casanova E, Salvadó MJ, Arola L, et al. Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet–induced obese rats. Nutr Res 2015; 35:337-345.
23. Baselga-Escudero L, Blade C, Ribas-Latre A, Casanova E, Suarez M, Torres JL, et al. Resveratrol and EGCG bind directly and distinctively to miR-33a and miR-122 and modulate divergently their levels in hepatic cells. Nucleic Acids Res 2014; 42:882-892.
24. Joven J, Espinel E, Rull A, Aragonès G, Rodríguez-Gallego E, Camps J, et al. Plant-derived polyphenols regulate expression of miRNA paralogs miR-103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice. BBA-Gen Subjects 2012; 1820:894-899.
25. Baselga-Escudero L, Blade C, Ribas-Latre A, Casanova E, Salvadó M-J, Arola L, et al. Chronic supplementation of proanthocyanidins reduces postprandial lipemia and liver miR-33a and miR-122 levels in a dose-dependent manner in healthy rats. J Nutr Biochem 2014; 25:151-156.
26. Okunrobo LO, Usifoh CO, Uwaya JO. Anti-inflammatory and gastroprotective properties of some chalcones. Acta Pol Pharm 2006; 63:195-199.
27. Yousefzadeh N, Jeddi S, Alipour MR. Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats. Arq Bras Cardiol 2016; 107:147-153.
28. Habibi P, Alihemmati AR, Nasirzadeh MR, Yousefi H, Habibi MR, Ahmadiasl N. Involvement of microRNA-133 and -29 in cardiac disturbances in diabetic ovariectomized rats. Iran J Basic Med Sci 2016; 19:1177-1185.
29. Wedick NM, Pan A, Cassidy A, Rimm EB, Sampson L, Rosner B, et al. Dietary flavonoid intakes and risk of type 2 diabetes in US men and women. Am J Clin Nutr 2012; 95:925-933.
30. Knekt P, Kumpulainen J, Jarvinen R, Rissanen H, Heliovaara M, Reunanen A, et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 2002; 76:560-568.
31. Karkhaneh L, Yaghmaei P, Parivar K, Sadeghizadeh M, Ebrahim-Habibi A. Effect of trans-chalcone on atheroma plaque formation, liver fibrosis and adiponectin gene expression in cholesterol-fed NMRI mice. Pharmacol Rep 2016; 68:720-727.
32. Shrime MG, Bauer SR, McDonald AC, Chowdhury NH, Coltart CE, Ding EL. Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J Nutr 2011; 141:1982-1988.
33. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A. Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a 1-year, double-blind, randomized, controlled trial. Diabetes Care 2012; 35:226-232.
34. Ding J, Li M, Wan X, Jin X, Chen S, Yu C, et al. Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease. Sci Rep 2015; 5:13729.
35. Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol 2014; 6:214-230.
36. Price NL, Ramírez CM, Fernández-Hernando C. Relevance of microRNA in metabolic diseases. Crit Rev Cl Lab Sci 2014; 51:305-320.
37. Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol 2009; 296:R1071-1077.
38. Zhang ZF, Zhang YQ, Fan SH, Zhuang J, Zheng YL, Lu J, et al. Troxerutin protects against 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD(+)-depletion. J Hazard Mater 2015; 283:98-109.
39. Kahyo T, Ichikawa S, Hatanaka T, Yamada MK, Setou M. A novel chalcone polyphenol inhibits the deacetylase activity of SIRT1 and cell growth in HEK293T cells. J Pharmacol Sci 2008; 108:364-371.