Targeting MMP-7 in idiopathic pulmonary fibrosis: An integrative in vivo and in silico evaluation of the therapeutic potential of Tylophora indica

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a degenerative pulmonary condition marked by a substantial accumulation of extracellular matrix and chronic inflammation. Matrix metalloproteinase-7 (MMP-7) is integral to fibrosis and likely a curative focus. This study investigates the therapeutic potential of Tylophora indica (T. indica) plant extract for treating IPF, utilizing in vivo and in silico approaches that target MMP-7. METHODS AND MATERIALS: T. indica extract was administered to a bleomycin-induced IPF mouse model at 200 and 300 mg/kg/day doses. Efficacy was evaluated through histological analysis and quantitative RT-PCR to measure MMP-7 expression. In silico molecular dynamics simulation and molecular docking identified bioactive compounds from T. indica that could inhibit MMP-7. ADMET profiling was used to evaluate these substances' pharmacological potential and safety. RESULTS: T. indica extract at 300 mg/kg/day significantly reduced fibrosis and inflammation, improving histopathological scores and lowering MMP-7 expression. In silico analysis identified pergularinine, tylophorine, quercetin, kaempferol, and tylophorinidine as potent MMP-7 inhibitors with stronger binding affinities than pirfenidone, a standard anti-fibrotic drug. Molecular dynamics simulations confirmed the stability of these interactions, and the compounds showed favorable safety profiles in ADMET assessments. CONCLUSION: T. indica extract demonstrated significant antifibrotic activity by downregulating MMP-7 expression and improving lung histopathology in the IPF mouse model. The identified phytochemicals show strong potential as natural MMP-7 inhibitors, suggesting T. indica as a prospective therapeutic agent for IPF. Additional clinical studies are required to validate these results.