Uncovering mechanisms of Baojin Chenfei formula treatment for silicosis by inhibiting inflammation and fibrosis based on serum pharmacochemistry and network analysis

Background: Baojin Chenfei formula (BCF), a Chinese herbal formula, has significant effects on improving the clinical symptoms of patients with silicosis. However, its active compounds and the underlying mechanisms have not yet fully been elucidated. Purpose: This study aimed to explore the underlying mechanisms of BCF in treating silicosis. Methods: The rat model of silicosis was developed via a single intratracheal instillation of SiO2 suspension to examine the therapeutic impacts of BCF on silicosis. Subsequently, the active compounds, targets, and mechanisms of BCF were analyzed based on serum pharmacochemistry and network analysis. Finally, the underlying mechanisms of representative compounds of BCF were validated in vitro experiments. Results: BCF significantly alleviated SiO2-induced silicosis in rats, evidenced by improved lung function, decreased pathological injury, and reduced inflammatory response and fibrosis. 19 active compounds were identified from the rat serum samples after BCF gavage. Subsequently, 299 targets for these 19 compounds in BCF and 257 genes related to silicosis were collected. 26 overlapping targets, including AKT1, TNF, IL6, MAPK3, EGFR, and others, were obtained from the intersection of the 299 BCF-related targets and 257 silicosis-associated genes. These overlapping targets mainly corresponded to glycyrrhetic acid and paeoniflorin and were mainly associated with positive regulation of smooth muscle cell proliferation, positive regulation of MAP kinase activity, and inflammatory response. In vitro experiments also demonstrated that the representative compounds of BCF (glycyrrhetic acid and paeoniflorin) could suppress inflammatory response by the MAPK pathway, and also inhibited fibroblast activation by the EGFR-PI3K-AKT pathway. Conclusion: Active compounds of BCF, such as glycyrrhetic acid and paeoniflorin, could suppress inflammatory response by the MAPK pathway and suppress fibroblast activation by the EGFR-PI3K-AKT pathway. These might be the mechanisms of BCF in treating silicosis.