基于网络药理学与数据挖掘探讨中药调节细胞焦亡用药规律  

Study on Medication Laws of Chinese Materia Medica in the Regulation of Pyroptosis Based on Network Pharmacology and Data Mining

作　　者：但文超 刘金垒[1] 何庆勇 张辉[1] 李安琪[1,2] DAN Wenchao;LIU Jinlei;HE Qingyong;ZHANG Hui;LI Anqi(Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]北京中医药大学,北京100029

出　　处：《中国中医药信息杂志》2021年第9期36-43,共8页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：中央本级重大增减支项目(2060302);北京市科技新星计划(Z181100006218035)。

摘　　要：目的探索中药调节细胞焦亡的物质基础及用药规律。方法通过整合GeneCards、OMIM、TTD、DrugBank、DisGeNET数据库获取细胞焦亡的作用靶点,以ADME参数和Lipinski规则为筛选条件,利用中药系统药理学技术平台筛选可作用于靶点的化合物及中药,并构建靶点-化合物、化合物-中药、靶点-化合物-中药网络。匹配中药的性味归经等信息,对用药规律进行分析。借助AutoDock Vina将网络中核心靶点与成分进行分子对接,以评估网络中靶点与化合物的结合强度,并进一步挖掘潜在的化合物靶点组合。结果共获得81个细胞焦亡的作用靶点,其中16个靶点可匹配到候选化合物,共收集到90个候选化合物,462味中药。频数统计结果显示,能够干预细胞焦亡的中药药味以苦、辛、甘为主,药性以寒居多,主要归肝、肺二经。分子对接共获得网内组合53个,Affinity较佳的有CASP3-rutin、CASP3-hesperidin、AKT1-diosgenin等;获得网外新组合109个,Affinity较佳的有AKT1-hesperidin、AKT1-rutin、AKT1-β-sitosterol等。所得核心靶点包括CASP3、BCL2、AKT1、IL1B、STAT3、EGFR,较为重要的成分有金雀异黄酮,(-)-表没食子儿茶素没食子酸酯、槲皮素、熊果酸等,较为重要的中药有麻黄、葛根、虎杖。结论本研究通过系统探讨中药干预细胞焦亡的物质基础,总结中药调节细胞焦亡的一般规律,可为中西医结合临床及干预细胞焦亡药物开发提供思路。Objective To analyze the material basis and medication laws of Chinese materia medica in the regulation of pyroptosis.Methods The target of pyroptosis was collected by integrating the GeneCards,OMIM,TTD,DrugBank,DisGeNET database.Using ADME parameters and Lipinski rule as the screening conditions,TCM system pharmacology technology platform was used to screen compounds and Chinese materia medica that can act on the target,and construct target-compound,compound-Chinese materia medica,target-compound-Chinese materia medica networks.Medication laws were analyzed by matching information such as the property,flavor and channel tropism of Chinese materia medica.With the help of AutoDock Vina,the core targets and components in the network were docked to evaluate the binding strength of the targets and compounds in the network and to further explore potential compound target combinations.Results A total of 81 targets for cell pyrolysis were obtained,of which 16 targets could be matched to candidate compounds.A total of 90 candidate compounds and 462 kinds of Chinese materia medica were collected.The results of frequency statistics showed that the Chinese materia medica that can interfere with cell pyrolysis were mainly bitter,pungent,and sweet,and the properties were mostly cold,which were mainly attributed to the liver and lungs meridians.A total of 53 intranet combinations were obtained for molecular docking.The better Affinity combinations included CASP3-rutin,CASP3-hesperidin,AKT1-diosgenin,etc.;109 new off-net combinations were obtained,and the better Affinity combinations were AKT1-hesperidin,AKT1-rutin,AKT1-β-sitosterol and so on.The core targets obtained included CASP3,BCL2,AKT1,IL1B,STAT3,EGFR,and the more important components were genistein,(-)-epigallocatechin-gallate,quercetin,ursolic acid,etc.The important Chinese materia medica were Ephedrae Herba,Puerariae Lobatue Radix,and Polygoni Cuspidati Rhizoma et Radix.Conclusion Through systematically analyzing the material basis of Chinese materia medica intervent

关 键 词：细胞焦亡 网络药理学 用药规律 新药研发 

分 类 号：R285[医药卫生—中药学] R34[医药卫生—中医学]