Acetylshikonin alleviates pulmonary fibrosis through inhibition of the STAT3 signaling pathway

Pulmonary fibrosis (PF) is a refractory lung disease characterized by excessive extracellular matrix (ECM) deposition accompanied by inflammatory injury. Acetylshikonin (ASH), a naphthoquinone derivative primarily sourced from the root of Lithospermum erythrorhizon, possesses a diverse array of biological properties, including antitumor and anti-inflammatory activities, yet its potential in mitigating PF remains unexplored. We found that ASH ameliorated bleomycin-induced lung dysfunction and reduced lung inflammation levels, Collagen deposition and Epithelial-mesenchymal transition (EMT) in mice. ASH also inhibited the TGF-β1-induced increase in ECM deposition and EMT and inhibited the migration of cultured cells. Notably, ASH inhibited STAT3 phosphorylation and nuclear translocation, and overexpression of STAT3 in MLE-12 cells reversed the effects of ASH on ECM deposition and cell migration. Collectively, our studies demonstrate that ASH alleviates PF through inhibition of the STAT3 signaling pathway and provide compelling evidence that ASH is a promising candidate drug for the treatment of PF.