Oxymatrine attenuates pulmonary fibrosis via APE1‑mediated regulation of the PINK1/Parkin pathway.

Abstract

Pulmonary fibrosis (PF) is a chronic, progressive lung disease characterized by impaired gas exchange and respiratory difficulties, which can ultimately lead to respiratory failure and mortality. The present study explored the therapeutic effects and underlying mechanisms of oxymatrine (OMT) in an 8‑week‑old C57BL/6 mouse model of bleomycin‑induced PF. The results demonstrated that OMT alleviated lung tissue damage, inflammation and collagen deposition, while promoting autophagy and restoring mitochondrial function. OMT achieved these effects by upregulating apurinic/apyrimidinic endonuclease‑1 (APE1) and activating the PTEN‑induced kinase 1 (PINK1)/Parkin pathway, both of which are key for mitochondrial autophagy. Furthermore, Lewis lung carcinoma mouse lung cancer cells were transduced with an adeno-associated virus containing small interfering RNA APE1 and a negative control, and the silencing efficiency was validated by reverse transcription‑quantitative PCR and western blotting. The results revealed a significant reduction in APE1 expression in the APE1 knockdown group compared with that in the negative control knockdown group. Immunohistochemistry and immunofluorescence confirmed that OMT increased the expression of APE1, PINK1 and Parkin while reducing markers of fibrosis, such as α‑smooth muscle actin and collagen type I α 1. However, silencing APE1 or inhibiting mitochondrial autophagy with mitochondrial division inhibitor‑1 reversed the beneficial effects of OMT, suggesting a key role for APE1 and the PINK1/Parkin pathway in its mechanism of action. These findings provide insights into the antifibrotic potential of OMT and highlight its potential as a basis for the development of new therapies for PF.