基于网络药理学及分子对接技术探讨“柴胡-香附”药对“异病同治”阿尔茨海默病和癫痫的研究  

Exploring Effects of “Chaihu(Bupleuri Radix)-Xiangfu(Cyperi Rhizoma)” on Alzheimer's Disease and Epilepsy Based on Network Pharmacology and Molecular Docking Technology

作　　者：朱小敏 陈炜[2] 洪煌忠 廖乃彬 ZHU Xaomin;CHEN Wei;HONG Huangzhong;LIAO Naibin(Guangxi University of Chinese Medicine,Nanning 530001,Guangxi,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi,China)

机构地区：[1]广西中医药大学,广西南宁530001 [2]广西中医药大学第一附属医院,广西南宁530023

出　　处：《实用中医内科杂志》2023年第11期8-13,I0002-I0005,共10页Journal of Practical Traditional Chinese Internal Medicine

基　　金：国家自然科学基金项目地区项目(82060844);广西中医药大学研究生教育创新计划项目(YCSY2022018);广西中医药大学第一附属医院学术团队建设项目(院字[2018]146号);广西高等学校高水平创新团队及卓越学者计划项目(桂教人才[2020]6号);广西中医脑病临床医学研究中心项目(桂科AD20238028)。

摘　　要：目的 采用网络药理学及分子对接的方法探究“柴胡-香附”药对治疗阿尔茨海默病(alzheimer disease,AD)和癫痫(epilepsy,EP)的作用机制,为“柴胡-香附”药对“异病同治”AD和EP提供循证医学依据。方法 通过中药系统药理学数据库与分析平台(TCMSP)检索柴胡与香附药物有效成分,并通过UniProt数据库得到药物靶点,利用GeneCards、OMIM数据库分别得到AD、EP相关疾病靶点,使用Cytoscape 3.7.2构建疾病-药物-成分-靶点网络;通过R语言对靶点进行GO富集分析和KEGG通路富集分析。将疾病-药物-成分-靶点网络的关键成分与交集靶点PPI网络关键靶点运用Pymol软件进行分子对接。结果 筛选得到柴胡-香附药对的有效成分31种(重复成分4种),相关药物靶点814个;AD疾病靶点1916个,EP疾病靶点2782个;药物与AD、EP直接相关的交集靶标分别为125、85个;柴胡-香附可能主要通过调控IL-17信号通路、AGE-RAGE信号通路及TNF通路等作用于AKT1、CASP3、TP53、VEGFA、ESR1、FOS、IL6、TNFH等靶点对阿尔茨海默病和癫痫发挥作用,关键靶点与核心成分分子对接大多可形成稳固结构。结论 柴胡-香附通过多靶点、多通路发挥了对AD和EP“异病同治”的药效作用。Objective To explore the mechanism of action of “Chaihu(Bupleuri Radix)-Xiangfu(Cyperi Rhizoma)” in the treatment of alzheimer disease(AD) and epilepsy(EP) by means of network pharmacology and molecular docking so as to provide a basis for “Chaihu(Bupleuri Radix)-Xiangfu(Cyperi Rhizoma)” for “homotherapy for heteropathy” of AD and EP.Method Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to retrieve the active ingredients of Chaihu(Bupleuri Radix) and Xiangfu(Cyperi Rhizoma),and got the drug target through the UniProt database.GeneCards and OMIM databases were used to obtain AD and EP related disease targets,respectively.And it constructed a disease-drug-ingredient-target network by using Cytoscape 3.7.2.GO enrichment analysis and KEGG pathway enrichment analysis of targets were performed by R language.The key components of the disease-drug-component-target network and the key targets of the intersection target PPI network were molecularly docked by using Pymol software.Results A total of 31 kinds of active ingredients(4 kinds of duplicate ingredients) of Chaihu(Bupleuri Radix)-Xiangfu(Cyperi Rhizoma) were screened,containing 814 related drug targets,1916 disease targets for AD and 2782 disease targets for EP.The intersection targets of drugs directly related to AD and EP were 125 and 85,respectively.Chaihu(Bupleuri Radix)-Xiangfu(Cyperi Rhizoma) may play a role in treating AD and EP mainly through regulating IL-17 signaling pathway,age-rage signaling pathway and TNF signaling pathway and acting on AKT1,CASP3,TP53,VEGFA,ESR1,FOS,IL6,TNFH and other targets.Most of the key targets and key components molecular docking can form a stable structure.Conclusion Chaihu(Bupleuri Radix)-Xiangfu(Cyperi Rhizoma) has exerted the pharmacodynamic effect of “homotherapy for heteropathy” on AD and EP through multiple targets and multiple pathways.

关 键 词：柴胡-香附 异病同治 阿尔茨海默病 癫痫 网络药理学 分子对接 

分 类 号：R271.43[医药卫生—中医妇科学]