Evening primrose and its compounds of 1-Oxohederagenin and remangilone C ameliorate bleomycin-induced pulmonary fibrosis by regulating ß-catenin signaling.

ABSTRACT

BACKGROUND: Pulmonary fibrosis (PF) is a progressive and severe respiratory disease for which there is still a lack of satisfactory treatment methods other than lung transplantation. Evening primrose (EP) is widely used in Chinese folk medicinal herbs, especially for the treatment of lung-related diseases. However, the protective effect of evening primrose against PF has yet to be reported. PURPOSE: This study explores the pharmacological effect of EP and its possible active components against PF from the perspectives of lung function, histopathological staining, and molecular biology assays. METHODS: Establishing a rat pulmonary fibrosis model using bleomycin to detect lung function, pathological changes, and collagen deposition. TGF-ß1 was used to establish an in vitro model of PF in BEAS-2B cells, and the active ingredients in evening primrose were screened. Then, the therapeutic effects of 1-Oxohederagenin (C1) and remangilone C (C2) derived from EP were observed in an in vivo model of bleomycin-induced PF, and the differentially expressed genes between the C1 and C2 treatment groups and the model group were screened with transcriptome sequencing. Finally, TGF-ß1-induced damage to HFL1 cell was used to explore the specific mechanisms by which C1 and C2 alleviate PF and the involvement of ß-catenin signaling. RESULTS: Evening primrose extract showed some ameliorative effects on bleomycin-induced PF in rats, manifested as reduced pathological damage and reduced collagen deposition. The chemical components of C1 and C2 potently ameliorated BLM-induced PF in animals and effectively inhibited fibroblast activation by interfering with ß-catenin signaling. CONCLUSION: Evening primrose extract has certain ameliorative effects on PF. In addation, C1 and C2 might be related with the suppression of fibroblast activation by inhibiting ß-catenin signaling.