Antifibrotic effect of AD-1 on lipopolysaccharide-mediated fibroblast injury in L929 cells and bleomycin-induced pulmonary fibrosis in mice

20(<i>R</i>)-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH₃-PPD, AD-1) is a dammarane ginsenoside that is isolated from <i>Panax notoginseng</i>. The present study aimed to explore its anti-pulmonary fibrosis (PF) effect <i>in vitro</i> and <i>in vivo</i>. L929 cells were treated with 10 μg mL^-1 lipopolysaccharide (LPS) to establish a PF model <i>in vitro</i> and mice were administered with 3.5 mg kg^-1 bleomycin (BLM) by endotracheal intubation to establish a PF model <i>in vivo</i> for investigating the anti-PF effect and its potential mechanism. The results demonstrated that AD-1 reduced the injury, extracellular matrix (ECM) buildup and α-smooth muscle actin (α-SMA) protein expression levels of L929 induced by LPS. Oral administration of AD-1 downregulated the expression of interleukins (such as IL-1β, IL-6 and IL-18), increased the expression of superoxide dismutase (SOD) and glutathione (GSH), reduced the lung coefficient and the content of hydroxyproline (HYP), and mediated the Bax/Bcl-2 protein ratio and P-p53, β-catenin and SIRT3 expression in the lung tissue of mice. Furthermore, AD-1 inhibited the expression levels of TGF-β1, TIMP-1 and α-SMA and reduced inflammatory cell infiltration and collagen deposition in the lung tissue of PF mice. These results indicated that AD-1 could alleviate PF both <i>in vitro</i> and <i>in vivo</i>, and the underlying mechanism may be related to the decrease in ECM deposition and inflammation, the enhancement of antioxidant capacity, and the mediation of lung cell apoptosis and the TGF-β1/TIMP-1/α-SMA signaling pathway, which provide a theoretical basis for the rehabilitation treatment of PF.