Targeting pulmonary fibrosis through Solanum xanthocarpum phytochemicals: A synergistic network pharmacology and docking investigation

BACKGROUND: Pulmonary fibrosis (PF) is a progressive, life-threatening disease characterized by excessive extracellular matrix deposition, leading to impaired lung function. Despite advancements in therapeutic interventions, the development of effective antifibrotic agents with minimal side effects remains a significant challenge. Solanum xanthocarpum (SLM) is a traditional medicinal plant used in multiple Ayurvedic formulations effective against cough, asthma, and inflammation. However, its molecular mechanisms are largely unexplored. OBJECTIVE: This study aims to identify potent phytochemicals from SLM with antifibrotic properties and elucidate their molecular mechanisms by targeting key regulatory proteins and pathways involved in PF through advanced computational approaches. METHODS: A systematic workflow was employed that incorporated network pharmacology, gene ontology, and pathway enrichment analysis. Databases such as IMMPT, GeneCards, DisGeNet, UniProt, SuperPred, and PubChem were used to identify targets and construct networks, including protein-protein interactions, pathway-target interactions, and phytochemical-pathway-target interactions. Key hub genes and pathways were identified, followed by molecular docking and MMGBSA binding free energy calculations to evaluate phytochemical-protein interactions, supplemented by 2D and 3D interaction analyses. RESULTS: A total of 131 overlapping targets (OLTs) between PF-related genes and phytochemical targets were identified. Pathway enrichment analysis revealed 14 critical signaling pathways, including PI3K-Akt, MAPK, and HIF-1. Molecular docking highlighted phytochemicals such as quercetin, apigenin, and solasonine, with high docking scores (-11.509, -10.104, and -9.189 kcal/mol, respectively) and strong binding free energies. These compounds demonstrated multiple interactions with key hub proteins, including MTOR, HIF1A, and NFKB1, as evidenced by detailed 2D interaction profiles involving critical amino acids. CONCLUSION: This study highlights the antifibrotic potential of Solanum xanthocarpum phytochemicals, including quercetin, apigenin, and solasonine, through their interactions with key proteins such as MTOR, HIF1A, and NFKB1, and their modulation of critical signaling pathways. The findings provide mechanistic insights and emphasize the role of computational tools in drug discovery, paving the way for future preclinical and clinical studies.