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

Abstract

BackgroundPulmonary 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. PurposeThis 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. MethodsEstablishing a rat pulmonary fibrosis model using bleomycin to detect lung function, pathological changes, and collagen deposition. TGF-β1 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-β1-induced damage to HFL1 cell was used to explore the specific mechanisms by which C1 and C2 alleviate PF and the involvement of β-catenin signaling. ResultsEvening 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 β-catenin signaling. ConclusionEvening primrose extract has certain ameliorative effects on PF. In addation, C1 and C2 might be related with the suppression of fibroblast activation by inhibiting β-catenin signaling.