Cajanus scarabaeoides, a wild legume traditionally used in medicine, is reputed for its anti-inflammatory properties, yet its active compounds and mechanisms remain poorly understood. This study employed an integrative in silico approach to elucidate its pharmacological basis and identify potential bioactive molecules. A total of 259 phytochemicals were retrieved from literature and the IMPPAT 2.0 database. Compounds with oral bioavailability (≥30%) and drug-likeness (≥0.18) were screened, and their ADMET profiles were predicted using pkCSM. Target prediction was performed through SwissTargetPrediction and GeneCards, followed by protein-protein interaction (PPI) network analysis to identify key targets. Gene Ontology (GO) and KEGG pathway enrichment analyses were conducted to determine major biological pathways, while molecular docking using AutoDock Vina assessed binding affinities. Hierarchical clustering characterized compound-target interaction patterns. Seven compounds (six flavonoids and one steroid) satisfied the pharmacokinetic criteria, all exhibiting favorable ADMET profiles. Network analysis revealed 54 target genes and eight hub proteins: TNF-α, AKT1, GSK3B, MMP9, HIF1A, BCL2L1, IL2, and MDM2. Enrichment analysis highlighted the PI3K/Akt-NF- κ B, FoxO, and p 53 signaling pathways as key anti-inflammatory routes. Docking and simulation studies demonstrated high binding affinities, particularly between daucosterol and isoorientin with AKT1 (-11.5 and -10.6 kcal/mol, respectively). Clustering analysis distinguished daucosterol from flavonoids, suggesting distinct yet complementary mechanisms. Overall, this study supports the traditional use of C. scarabaeoides for inflammation and suggests that daucosterol, isoorientin, and isoorientin 3′-O-methyl ether may represent promising multitarget anti-inflammatory scaffolds that warrant further validation through in vitro and in vivo studies.
Rokkam et al. (Sun,) studied this question.