熏倒牛抗惊厥活性的网络药理学研究及验证  

Study on the anticonvulsant activity of Biebersteinia heterostemon based on network pharmacology and animal experiments

作　　者：李明珠 岳会兰[3] 曲江勇[1] 刘增根 LI Mingzhu;YUE Huilan;QU Jiangyong;LIU Zenggen(School of Life Science,Yantai University,Yantai,Shandong,264005 P.R.China;School of Pharmacy,Hubei University of Chinese Medicine,Wuhan,Hubei,430065 P.R.China;Key Laboratory of Tibetan Medicine Research of Qinghai Province,Northwest Institute of Plateau Biology,Chinese Academy of Sciences,Xining,Qinghai,810001 P.R.China)

机构地区：[1]烟台大学生命科学学院,山东烟台264005 [2]湖北中医药大学药学院,湖北武汉430065 [3]中国科学院西北高原生物研究所青海省藏药研究重点实验室,青海西宁810001

出　　处：《华西药学杂志》2025年第2期145-152,共8页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:32170394);中国科学院西部之光青年学者A类项目(2019)。

摘　　要：目的通过网络药理学、分子对接、分子动力学模拟和动物实验验证,探究熏倒牛抗惊厥的潜在作用机制。方法采用Lipinski′s five rules和Swiss Target Prediction数据库筛选活性成分及其靶点,利用在线网站和数据库获得目标化合物与抗惊厥活性的交集靶点。从String数据库获得蛋白相互作用信息,用Cytoscape构建蛋白互作网络、筛选核心化合物。在DAVID在线平台,进行基因本体和基因组百科全书分析,对核心靶点进行分子对接和分子动力学模拟,并进行动物实验验证。结果从熏倒牛中筛选出31个活性成分,225个药物疾病交集靶点。熏倒牛抗惊厥主要涉及蛋白自磷酸化、信号转导、基因表达的负调控等生物过程,相关通路包括PI3K-AKT通路、AGE-RAGE通路、磷脂酶D通路等。活性化合物(木犀草素、野黄芩素、棕矢车菊素、TDF等)与作用靶点(PTGS2、MMP9)结合较紧密(结合能≤-10 kcal·mol~(-1)),且RMSD和Rg值波动小。熏倒牛精细组分(BHE)中高、中(65、25 mg·kg~(-1))剂量组能显著减少小鼠惊厥数、缩短小鼠惊厥持续时间,使惊厥潜伏期显著延长。结论熏倒牛中的黄酮类化合物(木犀草素、8-羟基蓟黄素、DMS、TDF等)主要作用于AKT1、EGFR、MMP9等核心靶点来发挥抗惊厥作用,其机制可能与抑制PI3K-AKT、AGE-RAGE、磷脂酶D等与惊厥发生的信号通路有关。OBJECTIVE To explore the potential mechanism of anticonvulsant effect of Biebersteinia heterostemon Maxim.(BHM)by network pharmacology,molecular docking,molecular dynamics simulation and animal experimental verification.METHODS Lipinski’s rule of five and Swiss Target Prediction database were used to screen the active components and their targets.The online website and database were used to obtain the intersection targets of the target compounds and anticonvulsant activity.The protein interaction information was obtained from the String database,and the protein interaction network was constructed by Cytoscape to screen the core compounds.On the DAVID online platform,GO and KEGG enrichment analysis were performed,molecular docking and molecular dynamics simulation were performed on the core targets,and animal experiments were performed.RESULTS Thirty-one active components and 225 drug-disease intersection targets were screened from BHM.BHM anticonvulsant mainly involved biological processes such as protein autophosphorylation,signal transduction,and negative regulation of gene expression.The related pathways included PI3K-AKT pathway,AGE-RAGE pathway,and phospholipase D pathway.The active compounds(luteolin,scutellarin,cyanidin,TDF,etc.)were closely bound to the targets(PTGS2 and MMP9)(binding energy≤-10 kcal·mol-1),and the RMSD and Rg values fluctuated little.Animal experiments showed that BHE medium-high(65 mg·kg-1)and medium(25 mg·kg-1)dose groups significantly reduced the number of convulsions in mice,shortened the duration of convulsions in mice,and significantly prolonged the latency of convulsions.CONCLUSION The flavonoids in BHM(luteolin,8-hydroxystigmaxanthin,DMS,TDF,etc.)mainly act on core targets such as AKT1,EGFR,and MMP9 to exert anticonvulsant effects.The mechanism may be related to the inhibition of PI3K-AKT,AGE-RAGE,phospholipase D and other signaling pathways associated with convulsions.

关 键 词：熏倒牛 抗惊厥 基因本体 基因组百科全书 网络药理学 分子对接 分子动力学模拟 黄酮类化合物 

分 类 号：R96[医药卫生—药理学]