α- Glucosidase Inhibitor Withania Coagulans Potentiates the effect of Metformin via regulating redox state and GLP-1 secretion in STZ-Induced Diabetic Mice Models.

Abstract

In the tale of human Metabolic regulation and balance, Diabetes mellitus emerges as an antagonist altering the intricate interplay between Insulin and Glucose. It falters this delicate equilibrium affecting an approximate of 6.1% (529 million people) of the global population and is expected to be greater than 10% by 2050. Different available anti-diabetic drugs including metformin pose health concerns and limitations. Withania coagulans and its ability to ameliorate the complications of diabetes via DPP-4 inhibition, GLP-1 enhancement, insulin production and intestinal glucose retention are reported. This study aimed at utilization of an alpha glucosidase inhibitor Withania Coagulans fruit extract to potentiate the effect of metformin via regulation of postprandial GLP-1 expression and regulation of redox state in mice models. Plant phytochemicals were confirmed via FTIR and GC-MS analysis. The extract efficacy was evaluated in mice via I.P administration and its combined effects with metformin were studied. The results obtained from in-vitro analysis and in-vivo analysis in STZ-induced diabetic mice models suggested that WC in combination with metformin improved GTT in mice (P<0.01), improved plasma insulin levels (p<0.01), GLP-1 levels (P<0.05) and Reduced MDA levels (P<0.01) by regulating redox state. The combined treatment significantly increased SOD and Catalase concentration indicating its increased antioxidant potential. The histological analysis clearly addresses the regain in structure of pancreatic beta cells due to synergistic effect of the WC and metformin. Withania coagulans can aid metformin’s ability to fight diabetes by improved regulation of diabetic biomarkers. Future studies on isolated bioactive compounds from WC extract, their mechanism of action can help develop a plant based anti-diabetic drug with reduced side effects to combat metabolic disorders.