Abstract Abstract: This article aims to explore the pharmacological mechanism of the kang-xian-miao-ling formula based on network pharmacology and animal experiments. Active ingredients and their targets from the formula were identified via database screening and were compared with targets associated with liver fibrosis to determine the core interaction targets. These core targets underwent enrichment analysis of protein-protein interaction (PPI) networks, gene ontology (GO) functions, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways. To validate the predictions derived from network pharmacology, a liver fibrosis model was established in rats using thioacetamide (TAA), with concurrent treatment using the formula. Histopathological changes in liver tissue were assessed through hematoxylin and eosin (HE) and Masson staining, while serum biochemical indicators and the expression of relevant genes in liver tissue were evaluated. The study identified 55 active ingredients in the kang-xian-miao-ling formula, with 98 interacting targets associated with liver fibrosis. PPI network analysis revealed 10 core targets, including AKT1, TNF, IL-6, TP53, IL-1β, MMP9, HIF1A, PTGS2, JUN, and ESR1, which are primarily implicated in cancer pathways, the PI3K/Akt signaling pathway, lipid metabolism, atherosclerosis, and TNF signaling pathways. Molecular docking experiments indicated that ingredients such as quercetin, gentianine, emodin, and luteolin exhibit favorable molecular binding affinity with core targets like AKT1 and PTGS2. Animal experiments demonstrated that, compared to the normal group, the model group rats exhibited significant fibrous collagen deposition and inflammatory cell infiltration in liver tissue, along with markedly increased serum levels of ALT, AST, and total bilirubin (TBIL). Additionally, inflammatory factors such as TNF-α, IL-6, and IL-1β were elevated, alongside increased mRNA expression levels of α-SMA, PIK3CA, AKT1, and TGF-β1 in liver tissue. In comparison to the model group, the treatment group exhibited improvements in liver tissue inflammation and collagen fiber deposition, alongside significantly reduced serum levels of ALT, AST, and TBIL. Additionally, there was a decrease in the expression of inflammatory factors and the mRNA levels of α-SMA, PIK3CA, and AKT1 in liver tissue. This study found that kang-xian-miao-ling formula may regulate the PI3K/Akt and TNF signaling pathways through the interaction of multiple components, targets, and pathways. It inhibits the release of inflammatory factors and promotes the degradation of collagen fibers, thereby effectively improving TAA-induced liver fibrosis in rats.
Key words: kang-xian-miao-ling formula; liver fibrosis; network pharmacology; PI3K/Akt signaling pathway; target molecule docking
（Acta Laser Biology Sinica, 2025, 34(3): 254-266）
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