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

Abstract

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.

Fig. 1

Hepatic tissue damages in the diabetic rats and their restoration by the oleanolic acid treatment. H&E, Bar: 40 μm. A-B No histopathological lesions in the healthy rats not administered with OA and administered with OA. C Degenerative changes and necrosis in the hepatocytes, inflammation cells in the diabetic rats not administered with OA. D Moderate degenerative changes and necrosis in the hepatocytes, inflammation cells in the diabetic rats administered with OA (DM + OA)