Bufei Huoxue capsule alleviates silicosis by inhibiting the activation of nucleotide-like receptor containing pyrin domain 3 inflammasome and macrophages polarization based on network pharmacology.

Objective: To predict the targets of Bufei Huoxue capsule (, BFHX) using network pharmacology analysis and to explore its effects and functional targets in a silicotic rat model.
Methods: The drug and disease targets were correlated through network pharmacology analysis to explore the targets and signaling pathways of BFHX affecting silicosis. NR8383 cells were cultured to verify the core genes and pathways. A rat model of silicosis was established to verify whether the mechanism behind SiO2-caused pulmonary fibrosis was alleviated by BFHX (0.82 g/kg) and how it affected key targets and pathways.
Results: Overlapping BFHX and silicotic gene targets produced 159 interactive targets, and 55 were screened by network topology analysis. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses suggested that BFHX could affect silicosis through the nucleotide-like receptor containing pyrin domain 3 (NLRP3) inflammasome. In NR8383 cells, the expression of core genes related to the NLRP3 inflammasome could be inhibited by BFHX treatment. BFHX reduced the degree of alveolitis and collagen deposition, attenuating pulmonary fibrosis in SiO2-induced rat model. Pulmonary macrophage pyroptosis after SiO2 exposure was observed under transmission electron microscopy. BFHX alleviated the morphological characteristics of pyroptosis. BFHX also reduced the expression of NLRP3, caspase-1, interleukin-1 beta (IL-1β), IL-18, IL-6, and tumor necrosis factor-alpha in lung tissues of silicotic rat model. BFHX affected the K ion content in bronchoalveolar lavage fluid when assessed by energy dispersive spectrometer testing. The expression of CD68+ and CD206+ were also reduced after BFHX intervention.
Conclusion: NOD-like receptor signaling is vital for BFHX's effects on silicosis. It exerts anti-pulmonary fibrosis effects by inhibiting pulmonary macrophage pyroptosis and polarization through NLRP3 inflammasome activation.