The systemic anti-diabetic effect of polyherbal formulation Varanadi Kashayam is mediated through GLP-1 secretion and DPP4 inhibition
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Background
Frontiers of health science increasingly emphasizes systems and network medicine approaches for managing complex lifestyle diseases such as diabetes. In this context, systemic targets like incretin hormones and their modulators - particularly DPP4 inhibitors - have gained prominence. Ayurveda , the Indian System of Medicine (ISM), with its clinically validated multicomponent formulations offers a valuable resource for integrative therapeutic strategies with systemic mode of action.
Purpose
The study investigates the incretin modulatory effect of Varanadi Kashayam (VA), an Ayurveda polyherbal formulation used in the clinical management of diabetes and its comorbidities.
Experimental approach
A high-fat diet induced Sprague-Dawley (SD) rat model was used to study the anti-diabetic, GLP-1 secretory, and anti-obesity effects of VA. In vitro studies using GLUTag cells assessed the GLP-1 secretion and DPP4 gene expression modulation; and studies using 3T3-L1 fibroblasts examined the anti-adipogenic effects. Computational methods including molecular docking and molecular dynamic simulations were used to identify the phytochemicals responsible for DPP4 inhibition.
Results
VA administration significantly improved fasting blood glucose and oral glucose tolerance in experimental animals, along with enhanced GLP-1 secretion. The in vitro results showed inhibition of DPP4 enzyme activity, increase in GLP-1 secretion and downregulation of DPP4 gene expression in GLUTag cells, and suppression of adipogenesis in 3T3-L1 fibroblast cells. Computational analyses ascertained Chebulinic acid, Chebulagic acid and Terchebin as top ranked phytochemicals responsible for DPP4 inhibition effect.
Conclusion
Combining in vitro , in vivo and in silico findings, this study provides valuable insight into the incretin modulatory effect of VA in treating diabetes and associated metabolic diseases.
Graphical Abstract
Highlights
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Varanadi Kashayam (VA) improved blood glucose and GLP-1 levels in diabetic rats.
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Inhibited DPP4 activity and gene expression in GLUTag cells.
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Suppressed adipogenesis and adipogenic markers in 3T3-L1 cells.
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Chebulinic acid, Chebulagic acid, and Terchebin identified as key DPP4 inhibitors.
