The protective effect of Hederagenin on pulmonary fibrosis by regulating the Ras/JNK/NFAT4 axis in rats.

As a respiratory disease with high morbidity and mortality, pulmonary fibrosis (PF) has been a serious threat to people's health. Hederagenin (HDG) is a pentacyclic triterpenoid saponin widely distributed in various plants. This study explored the role of HDG in Bleomycin (BLM)-induced PF and the molecular mechanism. The results showed that HDG reduced BLM-induced pulmonary dysfunction, pathological damage in a dose-dependent manner. Besides, HDG reduced BLM-induced collagen deposition by decreasing the levels of α-SMA, Collagen I and hydroxproline. Furthermore, HDG reduced the levels of inflammatory cytokines (TNF-α and IL-6), TGF-β1 and connective tissue growth factor (CTGF) in bronchoalveolar lavage fluid (BALF) or serum. Further mechanism analysis indicated that HDG inhibited the expression of Ras and phosphorylation of JNK and NFAT4 in a dose-dependent manner. However, the JNK pathway activator Anisomycin reversed this inhibitory effect. In conclusion, these findings suggest that HDG may be a potential target drug for PF therapy.