Objective To explore the mechanism of Shipi Yin for the treatment of liver cirrhosis based on network pharmacology, and to validate it through molecular docking technology and animal experiments. Methods (1) The effective active components and effect targets of Shipi Yin were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and liver cirrhosis⁃related targets were retrieved from the GeneCards® and OMIM® databases to identify intersection targets of the two. Cytoscape software was adopted to construct a “drug⁃component⁃effect target” network. For the intersection targets, protein⁃protein interaction network analysis (acquiring the core targets), Gene Ontology functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. Molecular docking validation was conducted between the effective active components and core target proteins. (2) Thirty⁃two rats were randomly divided into blank group or modeling group. The blank group received normal feeding, while the modeling group underwent liver cirrhosis modeling using a composite factor method. Successfully modeled cirrhotic rats models were randomly assigned to model group or treatment group. The treatment group received intragastric administration of Shipi Yin, while the blank and model groups received intragastric administration of equivalent normal saline, for a 4⁃week administration in total. Serum levels of four liver fibrosis indicators with respect to hyaluronidase (HA), type Ⅲ procollagen (PC⁃Ⅲ), type Ⅳ collagen (Ⅳ⁃C), laminin (LN), inflammatory factors in terms of interleukin (IL)⁃6, IL⁃1β, tumor necrosis factor (TNF)⁃α, and liver tissue oxidative stress factors including superoxide dismutase (SOD), glutathione peroxidase (GSH⁃Px) in liver tissues of rats were detected by ELISA. Real⁃time fluorescent quatitative PCR was used to measure the mRNA expressions of IL⁃6, IL⁃1β, AKT serine/threonine kinase 1 (AKT1), and TNF⁃α in liver tissues of rats. Results (1) A total of 118 effective active components and 197 corresponding effect targets were identified for Shipi Yin, along with 6483 liver cirrhosis⁃related targets, resulting in 158 intersection targets. The effective active components of Shipi Yin against liver cirrhosis included quercetin, kaempferol, naringenin, formononetin, 7⁃methoxy⁃2⁃methyl isoflavone, etc. The core targets of Shipi Yin for treating liver cirrhosis included IL⁃6, AKT1, IL⁃1β, TNF, TP53, STAT3, EGFR, JUN, MYC, Caspase⁃3. Shipi Yin against liver cirrhosis involved in biological processes such as positive regulation of gene expression, negative regulation of apoptotic process, positive regulation of cell proliferation, and inflammatory response, in cellular components including cytosol, nucleus, cytoplasm, plasma membrane, nucleoplasm, in molecular functions such as protein binding, identical protein binding, enzyme binding, DNA binding, protein homodimerization activity, and in signaling pathways like lipid and atherosclerosis, pathways in cancer, advanced glycation end product⁃receptor for advanced glycation end product signaling pathway in diabetic complications, and hepatitis B. A favorable binding activity was identified between the effective active components (quercetin, kaempferol, naringenin, formononetin, 7⁃methoxy⁃2⁃methyl isoflavone) and the core target proteins (IL⁃6, AKT1, IL⁃1β, TNF). (2) Compared with the model group, the treatment group exhibited decreased serum levels of HA, PC⁃Ⅲ, Ⅳ⁃C, LN, IL⁃6, IL⁃1β, TNF⁃α, whereas increased levels of SOD and GSH⁃Px in liver tissues, and downregulated mRNA expressions of IL⁃6, IL⁃1β, AKT1, and TNF⁃α in liver tissues (P<0.05). Conclusion Shipi Yin treats liver cirrhosis through multiple components, targets, pathways, and links, potentially by regulating processes such as inflammation, oxidative stress, ferroptosis, apoptosis, and autophagy.

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