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

  • Research article
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Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

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.

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Abbreviations

ALT:

Alanine amino transferase

AST:

Aspartate amino transferase

ALP:

Alkaline phosphatase

AMPK:

5′-adenosine monophosphate (AMP)-activated protein kinase

DM:

Diabetes mellitus

H&E:

Haematoxylin-Eosin

IDF:

International Diabetes Federation

IL-6:

Interleukin-6

MDA:

Malondialdehyde

NF-κB:

Nuclear factor kappa B

OA:

Oleanolic acid

ROS:

Reactive oxygen species

SIRT-1:

Sirtuin-1

STZ:

Streptozotocin

SOD:

Superoxide dismutase

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Funding

This work was supported by Coordinator of Scientific Research Projects [2021.M84.02.04] at Artvin Coruh University.

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Authors and Affiliations

  1. Faculty of Healthy Sciences, Department of Nutrition and Dietetics, Artvin Coruh University, 08000, Artvin, Turkey

    Hatice Iskender & Eda Dokumacioglu

  2. Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey

    Kubra Asena Terim Kapakin, Ismail Bolat & Behzat Mokhtare

  3. Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey

    Armagan Hayirli & Guler Yenice

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  1. Hatice Iskender
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Correspondence to Hatice Iskender.

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Iskender, H., Dokumacioglu, E., Terim Kapakin, K.A. et al. Effect of Oleanolic acid administration on hepatic AMPK, SIRT-1, IL-6 and NF-κB levels in experimental diabetes. J Diabetes Metab Disord 22, 581–590 (2023). https://doi.org/10.1007/s40200-022-01178-x

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