To systematically investigate the mechanism of Jisheng Shenqi Pills (JSP) in treating chronic renal failure (CRF) with network pharmacology and molecular docking methods.

Step 1, Component and target screening: The active ingredients and their corresponding targets of JSP were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and the High-throughput Experiment and Referenced Bioinformatics (HERB) database. Disease-related targets for CRF were retrieved from the Gene Cards (GeneCards), Online Mendelian Inheritance in Man (OMIM), and Disease Gene Network (DisGeNET) databases. And the intersecting targets between the drugs and the disease were identified. Step 2, Network construction and enrichment analysis: The protein-protein interaction (PPI) network was constructed using the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) database to identify core target genes. And the "herb-component-target-disease" network was visualized using the Cytoscape software. Functional enrichment analysis was then performed with the Gene Ontology (GO) database, and pathway enrichment with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Step 3, Validation by molecular docking: The molecular docking validation between the key active ingredients and core targets was performed using the AutoDock Vina software.

A total of 102 active ingredients of JSP were identified, corresponding to 232 potential targets. A total of 2, 153 targets were associated with CRF, resulting in 138 overlapping targets between the drug and the disease. Network analysis revealed that quercetin, kaempferol, wogonin, baicalein, and oleic acid were the key active ingredients. The core targets primarily included AKT1, TNF, IL6, MAPK1, TP53, CASP3, and BCL2. GO analysis suggested that the targets were mainly involved in inflammation, oxidative stress, apoptosis, and immune regulation. KEGG analysis showed enrichment in pathways related to AGE-RAGE, TNF, IL-17, PI3K-Akt, and lipids-atherosclerosis. Molecular docking confirmed the strong binding affinity between key components and core targets.

JSP may delay CRF progression by regulating key targets (AKT, MAPK, TNF) and signaling pathways (AGE-RAGE, PI3K-Akt) via flavonoid ingredients (quercetin, kaempferol), thereby exerting anti-inflammatory, antioxidant, inhibiting-apoptosis, and immunomodulatory effects. This illustrates the multi-component, multi-target, and multi-pathway advantages of traditional Chinese medicine (TCM) formulas, providing a theoretical basis for further mechanistic studies.