Integrating Chemical Profiling, In Vivo Study, and Network Pharmacology to Explore the Anti-inflammatory Effect of Pterocarpus dalbergioides Fruits and Its Correlation with the Major Phytoconstituents

Abstract

The purpose of this study is to explore the anti-inflammatory activity of Pterocarpus dalbergioides fruit extract (PFE) and the underlying mechanism. Chemical profiling using ultraperformance liquid chromatography/mass spectrometry identified 28 compounds in PFE (12 flavonoids, 5 fatty acids, 4 phenolic compounds, 3 alkaloids, 2 sesquiterpenes, and 2 xanthophylls). PFE (2 g/kg) significantly inhibited carrageenan-induced rat paw edema after 4 h of administration (42% inhibition). A network-based strategy and molecular docking studies were utilized to uncover the anti-inflammatory mechanism. Out of the identified compounds, 16 compounds with DL ≥ 0.18 and F ≥ 30% were selected using bioavailability ( F ) and drug-likeness (DL) metrics. The network analysis revealed that 90 genes are considered key targets for the selected compounds and linked to the anti-inflammatory effect. Among all compounds, linoleic acid was found to be the top-most active constituent as it targets maximum genes. Four targets (TNF, IL6, AKT1, and CCL2) among the top 10 genes were found to be the main target genes that may contribute to the anti-inflammatory potential of PFE. Furthermore, KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis revealed that PFE might regulate inflammation through five pathways: neuroactive ligand–receptor interaction, lipid and atherosclerosis, fluid shear stress and atherosclerosis, TNF signaling pathway, and rheumatoid arthritis. The docking study predicted the significant binding affinity between the top four active constituents (linoleic acid, 9-octadecenoic acid, 11,12,13-trihydroxy-9-octadecenoic acid, and rhamnetin-3- O -rhamnoside) and the selected target proteins (TNF and AKT1). The findings highlight PFE as a promising drug lead for controlling inflammation.