YF Reduces Alveolar Epithelial Cell Apoptosis and PF by Inactivating JAK2/STAT3

Pulmonary fibrosis (PF) is a chronic pulmonary disorder with unknown etiology and an irreversible course. Traditional Chinese medicine (TCM) possesses promising clinical benefits for PF treatment through a multi-component and multi-target approach. This study evaluates the efficacy of Yangyin Yifei Tongluo Wan (YF), a traditional formulation, in the treatment of PF, and further explores the underlying mechanism.

A bleomycin (BLM)-induced PF mouse model was established. Mice were administered with low-, medium-, and high-dose YF (1.5, 3, and 6 g/kg/d, respectively). The fibrosis degree of mouse lung tissues was evaluated by morphometric measurements and hydroxyproline (HYP) analysis. Network pharmacology-based bioinformatics were employed for constructing a network involving components, targets, and disease, and YF's potential mechanism and molecular targets for PF therapy were explored. This was further validated by TUNEL staining, Western blot, RT-qPCR, and ELISA in BLM-treated mice.

YF could relieve PF in BLM-treated mice in a dose-dependent manner, evidenced by a notable decrease in collagen deposition, and collagen I and III, HYP, fibronectin, vimentin, and α-SMA expressions. Network pharmacology revealed that JAK2/STAT3 signaling pathway-mediated alveolar epithelial cell apoptosis may be a potential therapeutic target for YF in treating PF. In vivo assays confirmed that YF's antifibrosis effect on BLM-induced PF was ascribed to the suppression of alveolar epithelial cell apoptosis and disruption of the JAK2/STAT3 signaling pathway.

YF can block alveolar epithelial cell apoptosis through inactivation of the JAK2/STAT3 signaling, subsequently enhancing the resolution of PF.

YF may be a promising therapeutic candidate for PF treatment.