18β-glycyrrhetinic acid ameliorates bleomycin-induced idiopathic pulmonary fibrosis via inhibiting TGF-β1/JAK2/STAT3 signaling axis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease with an unknown cause that has few treatment options. 18β-Glycyrrhetinic acid (18β-GA) is the main bioactive component in licorice, exhibiting anti-inflammatory and antioxidant effects, while also holding certain application value in the metabolism and regulation of steroids. In this study, we demonstrated that 18β-GA effectively alleviates bleomycin (BLM)-induced IPF by inhibiting the TGF-β1/JAK2/STAT3 signaling axis. In vivo experiments demonstrate that 18β-GA significantly attenuates pulmonary fibrosis progression by reducing lung inflammation, improving lung function, and decreasing collagen deposition. In vitro experiments reveal that 18β-GA inhibits the activation and migration of TGF-β1-induced fibroblasts. Furthermore, it regulates the expression of vimentin, N-cadherin and E-cadherin proteins, thereby inhibiting TGF-β1-induced epithelial-mesenchymal transition (EMT) in lung alveolar epithelial cells. Mechanistically, 18β-GA ameliorates pulmonary fibrosis by modulating the TGF-β1/JAK2/STAT3 signaling pathway in activated fibroblasts. Taken together, our findings demonstrate the potential and underlying mechanisms of 18β-GA in ameliorating IPF, emphasizing its potential as a novel therapeutic drug for the treatment of this devastating disease.