The compound artemisinin-hydroxychloroquine ameliorates bleomycin-induced pulmonary fibrosis in rats by inhibiting TGF-β1/Smad2/3 signaling pathway

Abstract

Pulmonary fibrosis (PF) is a lethal disease characterized by a progressive decline in lung function. Currently, lung transplantation remains the only available treatment for PF. However, both artemisinin (ART) and hydroxychloroquine (HCQ) possess potential antifibrotic properties. This study aimed to investigate the effects and mechanisms of a compound known as Artemisinin-Hydroxychloroquine (AH) in treating PF, specifically by targeting the TGF-β1/Smad2/3 pathway. To do this, we utilized an animal model of PF induced by a single tracheal drip of bleomycin (BLM) in Sprague-Dawley (SD) rats. The PF animal models were administered various doses of AH, and the efficacy and safety of AH were evaluated through pulmonary function testing, blood routine tests, serum biochemistry tests, organ index measurements, and pathological examinations. Additionally, Elisa, western blotting, and qPCR techniques were employed to explore the potential molecular mechanisms of AH in treating PF. Our findings reveal that AH effectively and safely alleviate PF by inhibiting BLM-induced specific inflammation, reducing extracellular matrix (ECM) deposition, and interfering with the TGF-β1/Smad2/3 signaling pathway. Notably, the windfall for this study is that the inhibition of ECM may initiate self-healing in the BLM-induced PF animal model. In conclusion, AH shows promise as a potential therapeutic drug for PF, as it inhibits disease progression through the TGF-β1/Smad2/3 signaling pathway.