Discussion on the Mechanism of Maguichaishi Formula in treating fever based on Network Pharmacology and Experimental Verification
Objective To explore the potential target of Maguichaishi formula in the treatment of fever by using network pharmacology,and to verify its antipyretic mechanism through molecular docking and experiments.Methods The compound components,latent targets and related targets of fever of each drug in Maguichaishi formula were searched through database and literature,and GO annotation,KEGG enrichment analysis and molecular docking were performed on the targets.The rat fever model was established by LPS,and the expression of TLR4/NF-κB/NOS2 signal pathway related genes and pathological changes of hypothalamic tissue with HE staining were observed to verify the results of network pharmacological analysis.Results 265 chemical constituents,435 potential targets and 110 cross targets with fever were screened out from Maguichaishi formula,involving mainly AGE-RAGE,IL-17,TNF,Toll like receptor signal pathway,etc.Molecular docking showed that NOS2,GABRA1,BCL2 and their corresponding active components could combine to form stable conformation.The experiment shows that Maguichaishi formula can significantly reduce the body temperature of febrile rats and inhibit TLR4,NF-κB p65,COX2,NOS2,GABRA1 mRNA gene expression and TNF-α,IL-1β,IL-6,NOS2,GABRA1serum level,further improve the inflammatory state of hypothalamic tissue.Conclusion Maguichaishi formula can play an antipyretic role through multiple components,multiple targets and multiple ways.The experiment confirmed that Maguichaishi formula can inhibit the relative expression of TLR4/NF-κB/NOS2 signal pathway mRNA,reduce the level of inflammatory factors in SD rats,and provide scientific basis for in-depth research on the objective diagnosis and treatment of Jingfang combination.
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