Salidroside alleviates the progression of idiopathic pulmonary fibrosis by regulating ferroptosis

红景天苷通过调节铁死亡来缓解特发性肺纤维化的进展。

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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 idiopathic pulmonary fibrosis (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 gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, suggests that ferroptosis may play a role in the development of pulmonary fibrosis. To test this hypothesis, transforming growth factor beta 1 (TGF-β1) was used to induce fibrosis in vitro, and levels of pulmonary fibrosis markers such as alpha-smooth muscle actin (α-SMA), fibronectin (FSN), and collagen (COL) were measured by enzyme-linked immunosorbent assay (ELISA). The results confirmed successful establishment of the pulmonary fibrosis model in vitro and indicated increased levels of ferroptosis markers, including glutathione (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 expression of phospholipase A2 group IVA (PLA2G4A) in the fibrosis model, which was reduced by salidroside, indicating that salidroside may regulate ferroptosis via the PLA2G4A gene.

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