Qingzao Jiufei Decoction in the Regulation of TGF-β/Smad Signaling in Idiopathic Pulmonary Fibrosis

This study aimed to investigate the therapeutic effects of Qingzao Jiufei Decoction (QJD) on idiopathic pulmonary fibrosis (IPF) and its regulatory mechanism involving the TGF-β/Smad signaling pathway. Rats were divided into six groups: control, model, pifenidone (PFD), QJD Low Dose (QJD-L), QJD Medium Dose (QJD-M), and QJD High Dose (QJD-H). IPF was induced using bleomycin. Histopathological and ultrastructural changes in the lung tissue were analyzed. Levels of α-smooth muscle actin (α-SMA), collagen I (COL-1), fibronectin (FN1), TGF-β1, Smad2/3, and p-Smad2/3 proteins were measured. A TGF-β1-induced HFL-1 cell model was used to investigate the effects of QJD on the expression of α-SMA, COL-1, and FN1. Additionally, the TGF-β1 signaling agonist SRI-011381 was used to further determine the role of the TGF-β/Smad signaling pathway. Results: In vivo, compared with the control group, rats in the model group showed significantly reduced dietary and water intake, along with an increased lung coefficient. Lung tissue showed infiltration of inflammatory cells, thickening of alveolar walls, and marked signs of fibrosis. Additionally, edematous alveolar type II epithelial cells with severe fibrosis were observed, characterized by swollen and deformed intracellular organelle structures and a reduced number of rough endoplasmic reticulum. Levels of α-SMA, COL-1, FN1, TGF-β1, and p-Smad2/3 were significantly elevated. Treatment with QJD or PFD markedly alleviated BLM-induced symptoms. In vitro, whereas TGF-β1 induction significantly upregulated the expression of FN1, COL-1, and α-SMA, these effects were significantly attenuated by QJD treatment. Activation of the TGF-β/Smad signaling pathway with the TGF-β1 agonist SRI-011381 increased FN1, COL-1, and α-SMA expression and aggravated pulmonary fibrosis. However, QJD reversed the fibrotic effects induced by SRI-011381, suggesting that QJD ameliorates pulmonary fibrosis by inhibiting TGF-β/Smad signaling pathway. The findings of this study suggest that QJD attenuates and reverses the progression of pulmonary fibrosis by modulating the TGF-β/Smad signaling pathway.