Utilising Network Pharmacology to Explore Underlying Mechanism of Astragalus membranaceus in Improving Sepsis-Induced Inflammatory Response by Regulating the Balance of IκBα and NF-κB in Rats

OBJECTIVE: The purpose of the present study was to explore the mechanism of Astragalus membranaceus in the treatment of sepsis. METHODS: We searched the active components and targets of Astragalus membranaceus using the TCMSP and BATMAN databases. Then, the GeneCards, MalaCards, and OMIM databases were used to screen out relevant targets of sepsis. The common targets of the former two gene sets were uploaded to the STRING database to create an interaction network. DAVID was used to perform KEGG enrichment analysis of the core targets. Based on the results of KEGG and previous studies, key pathways for the development of sepsis were identified and experimentally validated. RESULT: We obtained 3,370 sepsis-related targets in databases and 59 active components in Astragalus membranaceus through data mining, corresponding to 1,130 targets. The intersection of the two types of targets led to a total of 318 common targets and 84 core targets were obtained after screening again. The KEGG and previous studies showed that these 84 core targets were involved in sepsis by regulating TNF, MAPK, and PI3K pathways. TNF, MAPK8, NF-κB, and IκBα are crucial in sepsis. Experimental validation demonstrated that some markers in sepsis model rats were improved after the intervention with Astragalus granules and their chemical components. Among them, IL-1β, IL-6, and TNF-α in rat serum were reduced. The mRNA and protein expression of TNF-α, IL-6, MMP9, MAPK8, and NF-κB were reduced in rat blood. However, the mRNA and protein expression of IκBα and PI3K were increased in rat blood. CONCLUSION: The AST could affect the TNF, PI3K, and MAPK pathway cascade responses centred on IκBα and NF-κB, attenuate the expression of IL-6 and MMP9, and interfere with the inflammatory response during sepsis.