Unveiling the Immunopharmacological Mechanisms of Biejiajian Pills (BJJP) Underlying the Treatment of Hepatic Fibrosis: Insights From Network Pharmacology and Experimental Validation.

Biejiajian Pills (BJJP) have demonstrated certain therapeutic effects in the treatment of hepatic fibrosis (HF) in Traditional Chinese medicine practice. However, their underlying mechanism of action remains unclear. This study aimed to investigate the primary compounds of BJJP and their potential mechanisms in treating HF through network pharmacology and experimental validation. By integrating network pharmacology with RF, SVM-RFE, and LASSO algorithms, this study identified that the therapeutic effect of BJJP on HF may be mediated by two signature genes, LYN and CFTR, which were further validated using a validation set. Molecular docking results showed that the main compounds of BJJP, including six compounds such as kaempferol and baicalein, have a strong binding affinity with LYN and CFTR. Through the ssGSEA algorithm, we found that the proportions of six immune cell subsets, including M1 macrophages, M2 macrophages, and resting memory CD4+T cells, showed directional changes between the HF group and the control group, and these changes were significantly correlated with the expression of LYN and CFTR. Furthermore, 133 compounds in BJJP were characterized using UHPLC-HRMS. In vivo experiments confirmed that BJJP effectively ameliorated liver function-related biochemical indices and histopathological alterations in mice with HF, downregulated the expression levels of LYN and CFTR, reduced the infiltration of CD45+, CD8+, CD68+, and TNF-α+ cells, and elevated the proportions of CD4+ and CD163+ cells. Bioinformatics analyses combined with experimental validation have demonstrated that BJJP exerts therapeutic effects on HF by downregulating the expression of LYN and CFTR and modulating immune function.