Computational investigation of Pluchea indica mechanism targeting peroxisome proliferator-activated receptor gamma

Introduction: Pluchea indica is known to have diverse pharmacological properties, including
\nanti-inflammatory, antioxidant, antimicrobial, and anticancer activities. However, there is a
\npressing need to thoroughly investigate the molecular interactions between P. indica compounds
\nand peroxisome proliferator-activated receptor gamma (PPARG). This study aimed to elucidate
\nthe molecular mechanisms behind P. indica and PPARG, and its potential implications for
\ndiabetes mellitus.
\nMethods: The computational investigation employed Pharmacological Network pharmacology,
\nhomology modeling, deep learning docking, and molecular dynamics to explore the active
\ncompounds and targets within P. indica against the PPARG.
\nResults: Three active compounds were identified namely pinoresinol, syringaresinol, and
\nplucheoside A, all of which complied with the Lipinski rule of five. The deep learning-based
\npose scores were determined as follows: Pinoresinol 0.55, syringaresinol 0.32, and plucheoside A
\n0.44. Additionally, protein-protein interactions were observed with PPARG and associated with
\nthe PPAR signaling pathway. Molecular dynamics simulation analysis showed the stability of the
\nthree compounds over a 100 ns period. Free energy calculations using Molecular Mechanics-
\nGeneralized Born and Surface Area (MM-GBSA) yielded ΔG values of -44.39 kcal/mol, -51.83
\nkcal/mol, and -40.27 kcal/mol for pinoresinol, syringaresinol, and plucheoside A, respectively.
\nConclusion: Pluchea indica might be developed to treat various diseases, particularly those
\ninvolving the PPARG signaling pathway. It suggests the possibility of being developed as a
\nfocused medication for diabetes.