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.