Astragaloside IV combined with quercetin attenuates silica-induced pulmonary fibrosis by promoting autophagy and suppressing pyroptosis.

BACKGROUND: Silicosis, a prevalent occupational disease caused by exposure to silica particles, currently lacks effective treatment. Traditional Chinese medicine (TCM), with its millennia of clinical application, offers potential therapeutic solutions. This study aimed to investigate the therapeutic effects of astragaloside IV (ASV) combined with quercetin (QUE) in silicosis, particular focus on their possible mechanisms involving autophagy modulation and pyroptosis regulation. METHODS: Rat silicosis models were established through silica particle exposure to evaluate the therapeutic effects of ASV and QUE coadministration over 28 days. We assessed pulmonary inflammatory and fibrotic markers while simultaneously analyzing autophagy and pyroptosis-related indicators to elucidate the underlying mechanism. RESULTS: The ASV and QUE combination therapy significantly ameliorated silicosis pathology, demonstrating marked anti-inflammatory effects through the reduction of tumor necrosis factor alpha (TNF-α), transforming growth factor β1 (TGF-β1) and high mobility group box-1 (HMGB1) levels, while effectively attenuating pulmonary fibrosis as shown by decreased α-smooth muscle actin (α-SMA) and hydroxyproline (HYP) concentrations following 28 days of treatment. Mechanistic investigations revealed enhanced autophagy activity, evidenced by upregulated microtubule-associated protein 1 light chain 3 (LC3) II/I ratio and Beclin1 expression coupled with downregulated sequestosome 1 (SQSTM1/P62), along with suppressed pyroptosis as indicated by reduced interleukin-1β (IL-1β), interleukin-18 (IL-18), and Caspase-1 levels. CONCLUSION: ASV combined with QUE could alleviate silica-induced pulmonary inflammation and fibrosis in rats, with the protective mechanism potentially mediated through enhanced autophagy activation and suppressed pyroptosis pathway.