Integrative Network Pharmacology and Molecular Docking Analysis of Nyctanthes arbor-tristis and Polyalthia longifolia for Potential PCOS Therapy

Abstract

Polycystic ovary syndrome (PCOS) is characterized by interrelated reproductive, endocrine and metabolic disturbances. This study integrated phytochemical screening, protein-target prediction, protein–protein interaction (PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and molecular docking to investigate bioactive constituents of Nyctanthes arbor-tristis and Polyalthia longifolia. Four P. longifolia compounds and nyctanthic acid from N. arbor-tristis were prioritized. The compound–disease analysis identified 68 and 37 overlapping PCOS-associated targets, respectively, with PPARG and TNF prominent in both PPI networks. Steroid hormone biosynthesis was enriched in P. longifolia (12 genes; Benjamini-adjusted p = 1.18 × 10⁻¹⁰) and N. arbor-tristis (nine genes; adjusted p = 1.27 × 10⁻⁸). The PPAR signaling pathway included six genes in each plant-specific target set (adjusted p = 0.00378 and 0.000905, respectively). Fifteen ligand–protein docking complexes were examined using AutoDock Vina. Among the four CID-labelled ligands, minimum docking scores of −8.4 kcal/mol occurred in the 1TNF and 1XP1 complexes; a fifth ligand yielded a score of −7.6 kcal/mol with 9V8G. Residue-level interaction profiles included an ASP351 hydrogen bond in 1XP1 and GLN470 contacts in 9V8G. The combined results identified candidate steroidogenic and metabolic mechanisms that merit targeted biochemical and cellular evaluation.