Mechanism of Fuzheng Jiedu Huayu Decoction in the Treatment of Sepsis based on Network Pharmacology and Molecular Docking

Objective: Using network pharmacology and molecular docking techniques, we explored the active ingredients in Fuzheng Jiedu Huayu Decoction (FJHD) and predicted its potential mechanisms of action in treating sepsis, providing a theoretical basis for the clinical application of FJHD. Methods: Using the TCMSP platform to screen for active ingredients and their targets in FJHD; obtaining sepsis-related target genes using the GeneCards, OMIM, and TTD databases; intersecting drug targets with disease-related targets using the Venny 2.1.0 platform; constructing drug-active ingredient-target networks using Cytoscape 3.10.3 software; analyzing protein-protein interactions using the STRING platform to identify core targets; performing GO function and KEGG pathway enrichment analysis on the intersected targets using the DAVID database; and validating the binding affinity of key active ingredients with core targets through molecular docking using AutoDock Vina software. Results: A total of 86 active ingredients were screened out, including quercetin, β-sitosterol, kaempferol, stigmasterol and luteol. There are 122 intersecting targets of drug components and diseases, of which the core targets are TP53, TNF, AKT1, JUN and IL6. GO function and KEGG pathway enrichment analysis showed that the effect of FJHD on sepsis mainly involved in RNA polymerase II-mediated transcription, positive regulation of gene expression, and negative regulation of apoptosis. cellular components such as cytoplasmic matrix, extracellular matrix and extracellular region; Molecular functions such as protein binding, identical protein binding, and enzyme binding; Cancer pathways, lipid and atherosclerosis mechanisms, and AGE-RAGE signaling pathways are the main pathways. Molecular docking technology found that the minimum binding energy of the core active ingredient and the core target protein of the drug was <-5 kcal/mol. Conclusions: FJHD may exert its therapeutic effects on sepsis through a mechanism involving multiple components, multiple targets, and multiple pathways. Among these, quercetin, luteolin, stigmasterol, β-sitosterol, and kaempferol may be the primary active ingredients responsible for the therapeutic effects of FJHD. JUN, TP53, and IL6 may be the potential therapeutic targets for the decoction in treating sepsis. The main pathways through which FJHD may exert its effects on sepsis could include pathways in cancer, lipid and atherosclerosis mechanism, and the AGE-RAGE signaling pathway.