Abstract
Agonists/partial agonists of peroxisome proliferators-activated receptor gamma (PPAR gamma) are used in controlling type 2 diabetes mellitus (T2DM). We have identified a PPAR gamma agonist/partial agonist from traditional Indian medicinal plants for controlling T2DM using in silico and in vivo models. Molecular modeling and docking approaches were used in this study to identify potential plant compounds that suitably bound with PPAR gamma. Well-docked complex structures developed from molecular docking analysis were carefully chosen by molinspiration bioavailability and docking energy levels. Based on these results, the best docking poses were produced from the ligand-binding domain and their binding affinity was confirmed. Consequently, the plant molecule nymphayol was retrieved as a final candidate. Nymphayol was also studied for its effect on oral glucose tolerance, lipid profile, aminotransferases levels, and transcript level of PPAR gamma using in vivo biochemical analysis. Nymphayol showed well-docked complex with ARG 288 on ligand-binding domain of PPAR gamma (PDB ID: 2PRG). In molecular study, nymphayol has significantly increased PPAR gamma mRNA expression in adipose tissue compared to the diabetic control group. The effects of nymphayol on oral glucose tolerance, lipid profile, and aminotransferases level also showed significantly positive effects. These results indicated that nymphayol can be utilized as a potential candidate for developing novel partial agonist and antidiabetic drug targetting PPAR gamma.