Ginsenoside Rh4 alleviates idiopathic pulmonary fibrosis by enhancing the CXCL9–CXCR3 axis

Idiopathic pulmonary fibrosis (IPF), often likened to a “tumor-like disease,” proves more lethal than several malignancies. Although prior studies have demonstrated the lung-protective efficacy of ginsenosides, the precise mechanism underlying their alleviative effect on IPF remains elusive. In this study, we validated the efficacy of the ginsenoside Rh4 in alleviating IPF and delved into the underlying mechanisms. Our data showed that Rh4 intervention significantly reduced mortality and hydroxyproline (HYP) content in mice. It also alleviated the pathological process of IPF by ameliorating phenomena such as alveolar wall thickening induced by IPF. In addition, in vitro cellular experiments confirmed that ginsenoside Rh4 was effective in alleviating transforming growth factor-β1-induced IPF model. Further analysis showed that ginsenoside Rh4 significantly reduced collagen fiber production and deposition while inhibiting the coagulation cascade signaling pathway. In addition, ginsenoside Rh4 inhibited the epithelial-mesenchymal transition(EMT) pathway by promoting the CXCR3-CXCL9 axis, which ultimately alleviated IPF. In conclusion, our data strongly suggest that ginsenoside Rh4 has the potential to be an innovative prophylactic drug against IPF.