Antidiabetic effect of Dodonaea viscosa aerial parts in high fat diet and low dose streptozotocin-induced type 2 diabetic rats: A mechanistic approach

Abstract

Context: High fat diet (HFD) and low-dose streptozotocin (STZ) is an ideal model for type 2 diabetes mellitus (T2DM) that would closely reflect the natural history and metabolic characteristics of human T2DM and is also suitable for pharmacological screening.

Objective: The present study was designed to investigate the effect of the water extract (DVW) and the polar fraction of ethanol extract (DVE-4) of Dodonaea viscosa (L). Jacq. (Sapindaceae) on biochemical parameters in type 2 diabetes induced by a standardized HFD and low dose streptozotocin (25 mg/kg) in rats. Further, to elucidate the mode of action we evaluated its effects on a battery of targets involved in glucose homeostasis (in vitro studies).

Materials and methods: Different doses of DVW and DVE-4 were administered once daily for two weeks to HFD + STZ diabetic rats. Quantification of biomarker quercetin was done using HPLC.

Results and discussion: Both DVW and DVE-4 dose-dependently reduced blood glucose, serum insulin, homeostatic model assessment (HOMA), lipid profiles, and significantly improved glucose tolerance and HDL-c levels. In addition, the extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different, bioassays, DVW and DVE-4 showed inhibition of PTP-1B and at a concentration of 10 μg/mL showed 60 and 54.2% binding to PPARγ, respectively. Both extract/fraction exhibited stimulation of glucose uptake by skeletal muscles.

Conclusion: Taken together, these results suggest that DVW and DVE-4 inhibits HFD + STZ-induced insulin resistance, lipid abnormalities and oxidative stress indicating that these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.

Keywords::

• Dodonaea viscosa
• high fat diet
• STZ
• PPAR γ; PTB-1B
• glucose uptake

Acknowledgements

We thank the Head of the Department of Pharmacology, and Principal of Manipal College of Pharmaceutical Sciences, for providing necessary facilities. We also thank the Director of Natural Remedies, Bangalore, for providing facilities to carry out mechanistic studies.

Declaration of interest

We acknowledge financial support from Board of Research and Nuclear Sciences, Department of Atomic Energy, Government of India, grant vide no. 2003/36/27/BRNS/2014 dated 13.02.2004.