To explore the core targets,main active components and mechanism of Huanglian Jiedu Decoction in the treatment of sepsis.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was searched,with 黄连(Rhizoma Coptidis),黄芩(Radix Scutellariae),黄柏(Cortex Phellodendri),and栀子(Fructus Gardeniae) as keywords.According to bioavailability(OB)≥30% and drug-likeness(DL)≥0.18,the active components and targets of each Chinese medicinal material in Huanglian Jiedu Decoction were obtained.Online Mendelian Inheritance in Man(OMIM),GeneCards,and Therapeutic Target Database(TTD) were used to screen the targets of sepsis.Then the obtained predicted components and disease targets were input in Cytoscape to construct the network of Chinese medicinal material-components-disease-targets,and the core targets and main active components were screened.The protein protein interaction(PPI) network was plotted via STRING combined with Cytoscape and topological analysis was performed.After R language running,GO analysis and KEGG pathway annotation analysis were conducted on the core targets,with the thresholds of P<0.05 and Q<0.05,to screen the biological processes and signaling pathways with significant differences.Results:A total of 78 components and 841 targets of Huanglian Jiedu Decoction were screened,and 147 biological pathways were involved,including metabolic pathways such as tumor necrosis factor(TNF),chemokine,hypoxia-inducible factor 1(HIF-1),and apoptosis signaling pathways,and pathways related to the endocrine system such as AGE-RAGE signaling pathway in diabetic complications and endocrine resistance.Conclusion:Berberine,quercetin,kaempferol and other components in Huanglian Jiedu Decoction synergistically acted on the AGE-RAGE signaling pathway,TNF signaling pathway,etc.,which preliminarily revealed the complex multi-component,multi-pathway and multi-target synergistic mechanism of Huanglian Jiedu Decoction in the treatment of sepsis,and laid a theoretical foundation for future experimental verification.