Erchen decoction alleviates silicosis by attenuating ferroptosis and fibrosis in alveolar macrophages via modulating the P53/HMOX1 pathway

Ethnopharmacological relevance: Erchen decoction (ECD) has traditionally been employed as an adjunct therapy for respiratory diseases such as tracheitis, bronchitis, and chronic obstructive pulmonary disease (COPD) in China. However, its therapeutic effects and underlying mechanisms in treating silicosis remain unclear.

Aim of the study: This study aims to elucidate the protective mechanism of ECD against silica-induced pulmonary fibrosis, focusing specifically on Ferroptosis in alveolar macrophages (AMs).

Materials and methods: Silicosis animal and cellular models were established through silica (SiO₂) exposure to evaluate the therapeutic efficacy of ECD. The effects of ECD on fibrosis, polarization, and Ferroptosis in AMs were systematically evaluated using histopathology, cytokine assays, and Molecular Biology techniques.

Results: Animal experiments demonstrated that ECD significantly reduced silica-induced inflammatory infiltration, Collagen deposition, and fibrosis markers (α-SMA and Collagen-1) expression in mouse lung tissues. Metabolomic analysis identified active components in ECD serum, including quercetagitrin and hinokiol, which exhibited strong binding affinities with key Ferroptosis targets (P53 and HMOX1). Co-culture models confirmed that ECD suppressed fibroblast migration and activation via modulating AMs function, thereby reducing secretion of pro-inflammatory (IL-6) and pro-fibrotic (TGF-β) factors. Mechanistically, ECD inhibited silica-induced Ferroptosis in AMs, evident by reduced intracellular Fe²⁺, lipid peroxidation, and malondialdehyde (MDA) levels, increased GPX4 and xCT expression, and antioxidant activity mediated through the P53/HMOX1 axis.

Conclusions: ECD effectively ameliorates silica-induced silicosis progression by targeting Ferroptosis in AMs and regulating the P53/HMOX1 signaling pathway, highlighting its potential as an adjunct therapeutic option for silicosis.

Alveolar macrophages; Erchen decoction; Ferroptosis; Silicosis.