结合网络药理学与分子对接研究中药香囊干预慢性束缚应激诱导焦虑模型小鼠的作用机制  

Combining network pharmacology and molecular docking to investigate the effect mechanism of Chinese medicine sachet on a chronic restraint stress-induced anxiety model in mice

作　　者：徐智慧 于文欣 欧阳珺瑜 曾宇 XU Zhihui;YU Wenxin;OUYANG Junyu;ZENG Yu(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学中药学院,广东广州510006

出　　处：《广东药科大学学报》2024年第6期40-47,共8页Journal of Guangdong Pharmaceutical University

基　　金：广东药科大学2022年度广东省科技创新战略专项资金“攀登计划”(pdjh2022b0267);广西科技重大专项(桂科AA20302018-17)。

摘　　要：目的探究中药香囊对焦虑模型小鼠焦虑样行为的干预作用及其机制。方法采用慢性束缚应激法(CRS)建立焦虑小鼠模型,通过旷场、高架十字迷宫实验探讨中药香囊对小鼠焦虑样行为的影响,ELISA法检测小鼠海马和血清中5-羟色胺(5-HT)、皮质酮(CORT)水平。从TCMSP平台挖掘中药香囊活性成分作用靶点,OMIM、GeneCards、DisGeNET数据库获得焦虑疾病靶点。利用Venny平台获得成分-疾病的交集靶点,进行GO和KEGG富集,通过Cytoscape可视化分析构建“活性成分-靶点-通路”网络,并选取Degree较大的活性成分与关键靶点进行分子对接验证。结果中药香囊可以显著改善CRS小鼠的焦虑样行为,显著增加海马和血清中5-HT水平,显著降低血清中CORT水平。网络药理学结果显示中药香囊中多个活性成分(刺槐素、柚皮素、汉黄芩素等)可以作用于多个关键靶点(AKT1、SRC、ESR1、CASP3等),调控多条信号通路(癌症通路,PI3K-AKT信号通路等)发挥作用。分子对接结果显示活性成分(洋川芎醌、刺槐素、胡萝卜苷、芫花素、柚皮素、汉黄芩素)与关键核心靶点(SRC、ESR1、CASP3、EGFR)具有较高的结合活性。结论中药香囊可以改善CRS小鼠焦虑样行为和体内5-HT、CORT水平,可以通过多成分、多靶点、多通路干预焦虑症,为进一步的机制研究指明了方向。Objective To explore the intervention effect and mechanism of a Chinese medicine sachet on anxiety-like behavior in anxiety model mice.Methods The chronic restraint stress(CRS)method was used to establish an anxiety mouse model.Open field test and elevated plus maze investigated the effect of the Chinese medicine sachet on anxiety-like behavior in mice.The levels of 5-hydroxytryptamine(5-HT)and corticosterone(CORT)in the hippocampus and serum of mice were detected by ELISA.The targets of Chinese medicine sachet compounds were mined from the TCMSP platform,and the targets of anxiety diseases were obtained from OMIM,GeneCards,and DisGeNET databases.The Venny platform was used to obtain the component-disease intersection targets for GO and KEGG enrichment.The active ingredient-target-pathway network was constructed by Cytoscape.Active ingredients and key targets with larger Degree values were selected for molecular docking validation.Results Chinese medicine sachet significantly improved the anxiety-like behavior of CRS mice,increased the level of 5-HT in the hippocampus and serum,and reduced the level of CORT in serum.Network pharmacology showed that multiple active ingredients(acacetin,naringenin,wogonin,etc.)in the Chinese medicine sachet act on various key targets(AKT1,SRC,ESR1,CASP3,etc.)and regulate multiple signaling pathways(cancer pathway,PI3K-AKT signaling pathway,etc.).The molecular docking results showed that the active ingredients(senkyunone,acacetin,daucosterol,genkwanin,naringenin,and wogonin)have high binding activities to the key targets(SRC,ESR1,CASP3,and EGFR).Conclusion The Chinese medicine sachet can improve anxiety-like behavior and levels of 5-HT and CORT in CRS mice.It can intervene in anxiety through multiple components,targets,and pathways,providing direction for future mechanism research.

关 键 词：中药香囊 焦虑 慢性束缚应激模型 网络药理学 分子对接 

分 类 号：R965[医药卫生—药理学]