Analysis of Mechanism of Shenfu Injection in the Treatment of Sepsis-Associated Acute Kidney Injury Based on Network Pharmacology and Molecular Docking Technology
Abstract:Objective:To analyze the mechanism of Shenfu Injection in the treatment of sepsis-associated acute kidney injury( SA-AKI) based on network pharmacology and molecular docking technology. Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to predict the potential targets of Shenfu Injection. Disease targets for SA-AKI were retrieved from The Human Gene Database (GeneCards), Online Mendelian Inheritance in Man( OMIM),Pharmacogenetics and Pharmacogenomics Knowledge Base( PharmGKB), Therapeutic Target Database (TTD),and DisGeNET databases. Overlapping targets between Shenfu Injection and SAAKI were identified to determine the potential therapeutic targets of Shenfu Injection for this condition. Cytoscape 3.8.0 software was used to construct a "drug-component-target" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was employed to establish a protein-protein interaction (PPI) network of the key targets. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the therapeutic targets using R language. Molecular docking verification was also conducted. Results: A total of 89 active components and 89 corresponding targets of Shenfu Injection were obtained. There were 4 017 disease targets related to SA-AKI, resulting in 61 overlapping drug-disease targets. The core targets included estrogen receptor 1 (ESR1),interleukin (IL)-6,tumor necrosis factor (TNF),IL-1β,tumor protein p53 (TP53),prostaglandin-endoperoxide synthase 2 (PTGS2),caspase-3 (CASP3),and B-cell lymphoma 2 (BCL-2). The main active components were β-sitosterol, ginsenoside Rh2, β-elemene, palmitic acid, and salsolinol. KEGG pathway analysis involved key signaling pathways such as apoptosis, phosphatidylinositol-3- kinase (PI3K)/protein kinase B (Akt), TNF, and IL-17. Molecular docking results indicated good binding affinity between ginsenoside Rh2 and CASP3,TNF,and PTGS2. Conclusion:Shenfu Injection exerts its therapeutic effects on SA-AKI through a multi-component, multi-target, and multi-pathway synergistic mechanism, including mitigating the cytokine storm,inhibiting cell apoptosis,and ameliorating oxidative stress.