SALIDROSIDE ALLEVIATES THE PROGRESSION OF IDIOPATHIC PULMONARY FIBROSIS THROUGH REGULATING FERROPTOSIS

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial pneumonia of unknown etiology, characterized by recurrent acute lung injury. This leads to worsening dyspnea and lung function decline. Patients with IPF generally have a poor prognosis, often succumbing within 2-3 years of diagnosis, and the five-year survival rate is below 40%. Analysis of gene differences between raw and normal samples in the database, along with GO enrichment and KEGG analysis, suggests that ferroptosis may play a role in the development of pulmonary fibrosis. To test this hypothesis, TGF-β1 was used to induce fibrosis in vitro, and levels of pulmonary fibrosis markers α-smooth muscle actin (α-SMA), FSN, and Collagen (COL) were measured by ELISA. The results confirmed successful establishment of the pulmonary fibrosis model in vitro and indicated increased levels of ferroptosis markers GSH and iron accumulation. Salidroside, an extract from Rhodiola rosea, has been found to enhance glutathione levels in lung tissue, reduce oxidative stress, and decrease levels of α-SMA, FSN, COL, GSH, and iron in the model. These findings suggest that salidroside can mitigate pulmonary fibrosis by reversing ferroptosis. Additionally, we observed high PLA2G4A expression in the fibrosis model, which was reduced by salidroside, indicating that salidroside may regulate ferroptosis via the PLA2G4A gene.