Decoding Host Immune Modulation by Mimusops elengi Using Integrated Computational Approaches

Background Tuberculosis (TB) remains a major global threat, intensified by rising multidrug-resistant strains of Mycobacterium tuberculosis (Mtb). Host-directed therapies (HDTs) offer a promising approach to enhance immunity and improve treatment outcomes. Methods Mimusops elengi Linn., rich in triterpenoids, flavonoids, phenolics, and tannins, was investigated for its HDT potential using an integrated computational workflow. Network pharmacology identified key host immune and signaling targets, while enrichment analysis highlighted involvement in TB pathways. Molecular docking and 200-ns MD simulations were used to evaluate interaction stability. Results Network pharmacology identified targets—AKT1, MAPK14, IL6, TNF, STAT3, NFKB1, TLR2, TLR4, and CASP3—linked to TB pathogenesis. Enrichment analysis highlighted involvement in the TB pathway, PI3K–Akt, MAPK signaling, apoptosis, and mycolic-acid biosynthesis. Quercetin, myricetin, betulinic acid, friedelin, and lupeol were strong interactors, and MD simulations confirmed stable binding of the lead compound–PPARγ complex. Conclusion These findings suggest that M. elengi phytoconstituents possess multi-target, multi-pathway activity and hold promise as host-directed adjuncts for TB therapy, warranting further experimental validation.