空军军医大学学报2025，Vol.46Issue(11)：1433-1441,9.DOI:10.13276/j.issn.2097-1656.2025.11.006
基于网络药理学探讨加减解毒汤治疗流行性乙型脑炎的分子机制
Exploring the molecular mechanism of Jia-Jian-Jie-Du Decoction in the treatment of Japanese encephalitis based on network pharmacology
摘要
Abstract
Objective To investigate the therapeutic effect of Jia-Jian-Jie-Du Decoction on Japanese encephalitis(JE)and to identify the active ingredients and potential mechanisms of action of Jia-Jian-Jie-Du Decoction in the treatment of JE by using network pharmacology.Methods SPF-grade 6-week-old C57BL/6J mice were injected with the Japanese encephalitis virus(JEV)-P3 strain via the plantar surface to establish a JEV-infected mouse model.The model mice were randomly divided into three groups:the control group,the model group,and the treatment group.During the treatment period,the body mass,survival rate,and clinical symptoms of mice were evaluated.Mice were euthanized 2 h after the final administration,and histopathological changes were observed via HE staining.TNF-α and IL-6 levels in brain tissue were detected via ELISA,and JEV expression levels in brain tissue were detected via qRT-PCR.Subsequently,compounds from Jia-Jian-Jie-Du Decoction were screened based on the TCMSP and BATMAN-TCM databases,and the action targets of the components were predicted using the TCMSP platform.Resources from the GeneCards,DisGeNET,and OMIM databases were integrated to collect JE-related disease targets,and common targets between the components of Jia-Jian-Jie-Du Decoction and the disease were extracted using the bioinformatics online tool.Finally,a three-dimensional interaction network model incorporating traditional Chinese medicine,active ingredients,and action targets was constructed by using Cytoscape 3.8.2 software.The STRING database and Cytoscape 3.8.2 were used to construct a protein-protein interaction(PPI)network,screen core targets,and construct a network diagram.Metascape was used to perform GO and KEGG enrichment analysis on common targets.Results Compared with the control group,the mice in the model group exhibited significant decreased body mass and clinical symptoms,with all mice dying on the 16th day after modeling.Viral load and inflammatory factor levels in brain tissue were significantly elevated,and pathological changes were observed in HE-stained brain tissue.Compared with the model group,the treatment group significantly inhibited JEV-induced phenotypic changes in mice and suppressed viral load and inflammatory factor levels in brain tissue,with marked improvement in the pathological status of brain tissue(P＜0.05).Further screening identified 234 active ingredients in Jia-Jian-Jie-Du Decoction,with 141 common targets between the components and the disease.Core active ingredients included indirubin,diosgenin,β-sitosterol,quercetin,oroxylin A,irisolidone,isovitexin,kaempferol,etc.Ten core targets were screened from the PPI network,including ALB,AKT,TNF,IL-6,IL-1β,TP53,PTGS2,JUN,MMP9,and CASP3.GO and KEGG analyses revealed that it mainly involved inflammatory signaling pathways such as JAK-STAT,TNF,and IL-17.Conclusion The Jia-Jian-Jie-Du Decoction alleviates JEV-induced inflammatory responses and apoptosis through a multi-target and multi-pathway mechanism of action,thereby treating JE.关键词
流行性乙型脑炎/中药复方/加减解毒汤/药效评价/网络药理学/活性成分/作用机制/分子对接Key words
Japanese encephalitis/Chinese herbal formula/Jia-Jian-Jie-Du Decoction/efficacy evaluation/network pharmacology/active ingredients/mechanism of action/molecular docking分类
医药卫生引用本文复制引用
齐雯卉,李成文,李小强,宋凡..基于网络药理学探讨加减解毒汤治疗流行性乙型脑炎的分子机制[J].空军军医大学学报,2025,46(11):1433-1441,9.基金项目
国家自然科学基金面上项目(82270357) （82270357）
陕西省科技厅科技创新项目(2024RS-CXTD-71) （2024RS-CXTD-71）
空军军医大学博士学位论文课题(2024D11) （2024D11）
