Computational investigation of <i>Pluchea indica</i> mechanism targeting peroxisome proliferator-activated receptor gamma

Introduction: Pluchea indica is known to have diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. However, there is a pressing need to thoroughly investigate the molecular interactions between P. indica compounds and peroxisome proliferator-activated receptor gamma (PPARG). This study aimed to elucidate the molecular mechanisms behind P. indica and PPARG, and its potential implications for diabetes mellitus. Methods: The computational investigation employed Pharmacological Network pharmacology, homology modeling, deep learning docking, and molecular dynamics to explore the active compounds and targets within P. indica against the PPARG. Results: Three active compounds were identified namely pinoresinol, syringaresinol, and plucheoside A, all of which complied with the Lipinski rule of five. The deep learning-based pose scores were determined as follows: Pinoresinol 0.55, syringaresinol 0.32, and plucheoside A 0.44. Additionally, protein-protein interactions were observed with PPARG and associated with the PPAR signaling pathway. Molecular dynamics simulation analysis showed the stability of the three compounds over a 100 ns period. Free energy calculations using Molecular Mechanics-Generalized Born and Surface Area (MM-GBSA) yielded ΔG values of -44.39 kcal/mol, -51.83 kcal/mol, and -40.27 kcal/mol for pinoresinol, syringaresinol, and plucheoside A, respectively. Conclusion: Pluchea indica might be developed to treat various diseases, particularly those involving the PPARG signaling pathway. It suggests the possibility of being developed as a focused medication for diabetes.