Network pharmacology and in vitro studies demonstrate modulation of fibrotic pathways by Swertia chirayita in pulmonary fibrosis.

Various biological processes contribute to pulmonary fibrosis, which results in fibrotic foci that impede the exchange of gases between alveoli and capillaries. This study investigates the therapeutic mechanism in fibrotic foci reconfiguring via the TNF signaling pathway by potential Swertia chirayita (SC) components to treat pulmonary fibrosis by network pharmacology, in silico, and in vitro studies. The targets of LC-MS/MS analyzed SC components were used to build a protein-protein interaction network in Cytoscape and predicted key targets and signalings. The molecular docking, dynamics (MD) simulation, and principal component analysis (PCA) were performed to predict the potential interactions between components and their targets. In vitro studies, such as cell migration, E-cadherin immune fluorescence assay, and western blot analysis were performed in NIH3T3 and A549 cells with or without TGFβ1 stimulation. The network pharmacology of SC revealed nine key targets, and the pathway analysis found that these targets are implicated in TNF-α signaling. The main components of SC have substantial binding affinities, as shown by molecular docking. Furthermore, MD simulation and PCA predict that bellidifolin, gentiopicroside, and mangiferin will substantiate the anti-fibrotic effect. SC inhibited fibroblast migration and differentiation, epithelial to mesenchymal transition, and TNF-α downstream markers like NF-κB/p-NF-κB. In vitro studies confirmed the network pharmacology and docking predictions that SC can modulate fibrotic foci by acting through the TNF-α signaling pathway.