Combination Treatment of Timosaponin BII and Pirfenidone Attenuated Pulmonary Fibrosis Through Anti-Inflammatory and Anti-Fibrotic Process in Rodent Pulmonary Fibrosis Model and Cellular Epithelial–Mesenchymal Transition Model

Pulmonary fibrosis (PF) is a progressive lung disease with a poor prognosis. Pirfenidone (PFD) can slow down the decline of lung function, but defects in efficacy and accompanying side effects limit its application; hence, implementing methods including combination therapy might be a viable option. Given this, we hypothesized that combining timosaponin BII (TS BII) with PFD might offer a more effective treatment approach. Bleomycin-induced rodent PF model and TGF-β1-induced cellular epithelial-mesenchymal transition (EMT) model were applied in the study. The results showed that the combination of TS BII and PFD was more effective in reducing the production of IL-1β, TNF-α, collagen fibers, hydroxyproline, and MDA. Moreover, the combination treatment could better restore levels SOD and GSH-Px. In addition, TS BII combined with PFD could downregulate the expression of NF-κB and the ratio of p-IκBα/IκBα, and modulate the aberrant expression of epithelial-mesenchymal transition markers. In addition, the combination treatment could regulate the intestinal flora of PF mice. It is worth noting that among the above results, there were significant differences (<i>p</i> < 0.05) between the combination group and either the TS BII or PFD monotherapy group. These findings indicate that the combination of TS BII and PFD has a synergistic effect in the treatment of PF and represents a promising treatment strategy.