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

Abstract

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. Twenty-eight male Sprague Dawley rats were first subjected to either no diabetes induction (healthy) or diabetes induction by i.p. injection of 50mg/kg streptozotocin. Then rats in both groups were treated with either tap water or OA (5mg/kg) within 1 ml tap water by oral gavage for 21 days. 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. The OA treatment can be considered to alleviate oxidative stress and reduce severity of inflammation in hepatocytes in the diabetic subjects.