Effect of Oleanolic acid administration on hepatic AMPK, SIRT-1, IL-6 and NF-κB levels in experimental diabetes

• Published in: Journal of diabetes and metabolic disorders
• Main Authors: Iskender, Hatice, Dokumacioglu, Eda, Terim Kapakin, Kubra Asena, Bolat, Ismail, Mokhtare, Behzat, Hayirli, Armagan, Yenice, Guler
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 28.01.2023
• Subjects: Adenylic acid; Antioxidants; Dextrose; Glucose; Glucose metabolism; Interleukins; Physiological aspects; Protein kinases; Streptozocin
• ISSN: 2251-6581; 2251-6581
• DOI: 10.1007/s40200-022-01178-x

Objectives Diabetes mellitus (DM) is an important public health problem all over the world, considering its complications and increasing prevalence. Oleanolic acid (OA) has anti-diabetic property via modulating glucose metabolism and acting as 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) / Sirtuin-1 (SIRT-1) activator and Interleukin 6 (IL-6) / Nuclear factor kappa B (NF-κB) inhibitor. This research questioned if the OA treatment amliorates the hepatic inflammatory profile in the diabetic rats. Methods Twenty-eight male Sprague Dawley rats were first subjected to either no diabetes induction (healthy) or diabetes induction by i.p. injection of 50 mg/kg streptozotocin. Then rats in both groups were treated with either tap water or OA (5 mg/kg) within 1 ml tap water by oral gavage for 21 days. Results The diabetic rats had higher hepatic MDA (2.88x) and serum AST (2.01x), ALP (2.22x), and ALT (4.27x) levels and 50% lower hepatic SOD level than the healthy rats. The OA treatment significantly reversed these antioxidant parameters in the diabetic rats. The diabetic rats had lower AMPK (85%) and hepatic SIRT-1 (47%) levels and higher hepatic NF-κB (53%) and IL-6 (34%) levels than the healthy rats. Comparing with the health rats, the OA treatment increased hepatic SIRT-1 level, but tended to increase hepatic AMPK level and decrease hepatic NF-κB and IL-6 levels in the diabetic rats. It was also partially effective to ameliorate degenerative changes and necrosis in the diabetic rats. Conclusion The OA treatment can be considered to alleviate oxidative stress and reduce severity of inflammation in hepatocytes in the diabetic subjects. Keywords: AMPK, Diabetes, Inflammation, Oleanolic acid, SIRT-1