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Effect of Oleanolic acid administration on hepatic AMPK, SIRT-1, IL-6 and NF-κB levels in experimental diabetes
Hatice Iskender1, Eda Dokumacioglu1, Kubra Asena Terim Kapakin2
1Faculty of Healthy Sciences, Department of Nutrition and Dietetics, Artvin Coruh University, 08000 Artvin, Turkey.
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.
Insights
Oleanolic acid (OA) treatment in diabetic rats reduced oxidative stress and liver inflammation. OA helped reverse harmful changes in antioxidant levels and inflammatory markers, improving liver health in diabetic subjects.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Diabetes mellitus (DM) poses a global health challenge due to its complications and rising prevalence.
- Oleanolic acid (OA) exhibits anti-diabetic properties by influencing glucose metabolism and acting on key signaling pathways.
- OA modulates 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and Sirtuin-1 (SIRT-1), while inhibiting Interleukin-6 (IL-6) and Nuclear Factor kappa B (NF-κB).
Purpose of the Study:
- To investigate the potential of Oleanolic acid (OA) in ameliorating the hepatic inflammatory profile in streptozotocin-induced diabetic rats.
- To assess the impact of OA on oxidative stress markers and inflammatory pathways in the liver of diabetic subjects.
Main Methods:
- Twenty-eight male Sprague Dawley rats were used, with diabetes induced via streptozotocin injection.
- Diabetic and healthy rats received either tap water or Oleanolic acid (5 mg/kg) via oral gavage for 21 days.
- Hepatic and serum parameters, including oxidative stress markers (MDA, SOD) and inflammatory markers (AST, ALP, ALT, AMPK, SIRT-1, NF-κB, IL-6), were analyzed.
Main Results:
- Diabetic rats exhibited elevated hepatic MDA and serum AST, ALP, and ALT, alongside reduced hepatic SOD levels.
- OA treatment significantly reversed these oxidative stress parameters in diabetic rats.
- OA administration increased hepatic SIRT-1, tended to increase AMPK, and decreased hepatic NF-κB and IL-6 levels in diabetic rats, partially ameliorating degenerative changes.
Conclusions:
- Oleanolic acid (OA) treatment demonstrates efficacy in alleviating oxidative stress in diabetic subjects.
- OA helps reduce the severity of inflammation in hepatocytes of diabetic rats.
- The findings suggest OA as a potential therapeutic agent for managing hepatic inflammation associated with diabetes.
