Tgr5 receptor activation by oleanolic acid: molecular docking evidence of a natural compound in Metabolic regulation

Metabolism-related studies have increasingly focused on natural products and their biotechnological potential. In this context, the present study investigates the molecular interaction between oleanolic acid and the G protein-coupled bile acid receptor 1 (TGR5), a membrane-bound receptor involved in metabolic regulation, with potential therapeutic implications for diabetes and metabolic syndrome. Oleanolic acid is a naturally occurring triterpenoid found in various plant-based foods and medicinal herbs, while TGR5 is endogenously expressed throughout the body, with higher expression levels in the liver, intestine, stomach, spleen, and brown adipose tissue. To explore this interaction in silico, three-dimensional structures of both molecules were retrieved from structural databases, and molecular docking simulations were performed using algorithm-guided software to generate stable receptor-ligand complexes. The docking results revealed that oleanolic acid exhibits specific binding affinity for a distinct site on the TGR5 receptor, forming six stable chemical interactions. These interactions suggest a favorable energetic stabilization of the receptor-ligand complex, supporting the potential role of oleanolic acid as a positive modulator of TGR5 activity. The reproducibility and strength of the interaction indicate that oleanolic acid may contribute to beneficial metabolic effects through TGR5 activation, reinforcing its potential utility in the development of therapeutic strategies targeting obesity and related metabolic disorders.