Network pharmacology, molecular docking, and molecular dynamics simulation study of phytoconstituents from Baliospermum solanifolium roots for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Background Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), recently reclassified as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), are progressive metabolic-inflammatory disorders with limited therapeutic options. The roots of Baliospermum solanifolium (Burm.) Suresh have traditionally been used to treat hepatic disorders, although the molecular mechanisms underlying this use remain unclear. Purpose This study investigated the potential multi-target mechanisms of phytoconstituents from B. solanifolium roots in NAFLD and NASH using an integrated approach combining network pharmacology, transcriptomic analysis, molecular docking, and molecular dynamics simulations. Methods Twenty-three phytoconstituents isolated and structurally characterized from B. solanifolium roots were identified through a systematic review, and 575 unique targets were predicted. These targets were intersected with 829 upregulated genes obtained from human liver transcriptomic datasets (GSE130970, GSE135251, and GSE162694). Overlapping targets were analyzed using protein-protein interaction (PPI) networks and GO/KEGG enrichment analyses, followed by molecular docking and molecular dynamics simulations. Results Fifty overlapping targets were identified. PPI analysis revealed key hub targets, including PTGS2, CCR2, LGALS3, and FPR1, which are associated with inflammation, immune regulation, extracellular matrix remodeling, and fibrogenesis. Functional enrichment analysis identified biological processes related to cellular stress responses and inflammation. Molecular docking revealed favorable predicted binding affinities, particularly for baliosolanone B, baliospermin A, spruceanol, and baliospermin B toward PTGS2, LGALS3, FPR1, and CCR2, respectively. Molecular dynamics simulations supported the structural stability of prioritized complexes over 100 ns, particularly baliosolanone B-PTGS2 and baliospermin A-LGALS3 complexes. Conclusion Phytoconstituents from B. solanifolium roots may represent candidate contributors to the predicted modulation of inflammatory, immune, and fibrotic pathways involved in NAFLD/NASH progression, requiring experimental validation.