In Silico Exploration of Ayurvedic Extract for Targeting Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Via GPR120 and GPR40.

Abstract

Introduction: Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of hyperglycemia, often coexisting with Non-Alcoholic Fatty Liver Disease (NAFLD), as both share disrupted glucose and lipid metabolic pathways. The study aimed to explore the antidiabetic and hepatoprotective potential of active phytoconstituents from Tinospora cordifolia, Phyllanthus niruri, and Picrorhiza kurroa, focusing on their interaction with GPR120 and GPR 40 receptors through network pharmacology and molecular docking approaches.

Method: A combined extract of T. cordifolia, P. niruri, and P. kurroa was prepared following the Ayurvedic pharmacopoeia standards. Phytoconstituents were identified using High-Performance Thin-Layer Chromatographic (HPTLC) and mass spectroscopy. Network pharmacology analysis predicted mechanisms of action involving PI3-kinase, Protein Kinase C, and PI3K-Akt signaling pathways, targeting GPR120 and GPR40. Molecular docking was conducted for 31 identified compounds, and pharmacokinetic (ADMET) properties of the key hits were evaluated.

Results: Molecular docking identified six compounds with strong binding affinities to GPR 120 and 40. Among these, ferulic acid, caffeic acid, and cinnamic acid exhibited significant binding to GPR40 with docking scores of -10.68, -9.991, and -7.580 kcal/mol, respectively. Similarly, veronicoside, malic acid, and corilagin demonstrated strong interaction with GPR120, with docking scores of -8.95, -7.32, and -9.21 kcal/mol. The combined extract contained cinnamic acid and corilagin as major phytoconstituents, supported by favourable ADMET properties. The analysis highlighted their role in modulating glucose and lipid metabolism via key signaling pathways, corroborating their antidiabetic and hepatoprotective potential.

Conclusion: his study identifies cinnamic acid and corilagin as promising candidates for natural therapeutics targeting T2DM and NAFLD. The translational potential of T. cordifolia, P. niruri, and P. kurroaprovide further experimental validation to confirm their clinical efficacy in modulating metabolic pathways.