基于拓扑指数的QSAR法探讨脑泰方中抗脑血栓关键活性成分簇  

Exploration of key active component clusters in Naotaifang for anticerebral thrombosis by QSAR method based on topological index

作　　者：张玉超 钟鹏英 夏凡 李世雄 李璎峪 葛金文 刘文龙[1,2] 张喜利 ZHANG Yu-chao;ZHONG Peng-ying;XIA Fan;LI Shi-xiong;LI Ying-yu;GE Jin-wen;LIU Wenlong;ZHANG Xi-li(College of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Key Laboratory of Druggability and Preparation Modification of TCM,Changsha 410208,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]中药成药性与制剂制备湖南省重点实验室,湖南长沙410208

出　　处：《中草药》2023年第3期877-885,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81874344);湖南省自然科学基金项目(2021JJ30514);湖南省中医药管理局项目(2021073),湖南省中医药管理局项目(2021204);长沙市自然科学基金项目(kq2208191)。

摘　　要：目的基于定量构效关系(quantitative structure-activity relationship,QSAR)法探讨脑泰方中抗脑血栓的关键活性成分簇。方法利用中药系统药理学数据库与分析平台(TCMSP)及检索国内外相关文献,整理脑泰方单味中药和抗血栓化学药的化学成分信息集,计算各类化学成分的0~8阶/8种子图类型的分子连接性指数(molecular connectivity index,MCI)并构建相应矩阵,运用夹角余弦法分别对脑泰方中成分与抗血栓化学药之间的MCI相似度进行评价,并利用Sybyl-X2.1软件将相似度排名前5的成分与核心靶点对接验证。结果脑泰方中所含成分与抗血栓化学药的MCI相似度在0.3006~0.9978,其中毛蕊异黄酮(0.9961)、洋川芎内酯M(0.9978)、白僵菌素(0.9969)、肌苷(0.9927)为脑泰方中相似度最大的成分簇,且与脑血栓相关蛋白的total score≥5,显示出较强的结合能力。推断出黄芪中的黄酮类化合物毛蕊异黄酮、川芎中的苯酞类化合物洋川芎内酯M、僵蚕中的氨基酸类化合物白僵菌素、地龙中的核苷类化合物肌苷为脑泰方中发挥抗血栓作用的主要活性分子簇。结论所建立的基于MCI相似度评价法能科学地高通量筛选中药及复方功效活性成分簇,与现有的网络药理学等研究方法相得益彰,也为中西药结合研究提供新的思路。Objective To explore the key active component clusters in Naotaifang(脑泰方)for anti-cerebral thrombosis based on quantitative structure-activity relationship(QSAR)method.Methods The chemical composition information set from single TCM in Naotaifang and antithrombotic western medicines were sorted out by using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and relevant literatures at home and abroad,and the molecular connectivity index(MCI)matrix of 0-8 order/8 seed map types of various chemical components was calculated.The MCI similarity between the components in Naotaifang and antithrombotic western medicines were evaluated by the included angle cosine method,and Sybyl-X2.1 software was used to verify the docking of the top five components with the core targets.Results The MCI similarity between the components contained in Naotaifang and antithrombotic western medicines ranged from 0.3006 to 0.9978.Among them,calycosin(0.9961),senkyunolide M(0.9978),beauvericin(0.9969)and inosine(0.9927)were the components with the highest similarity in Naotaifang,and the total score of cerebral thrombosis-related proteins was≥5,showing strong binding ability.It was inferred that calycosin of flavonoids in Huangqi(Astragali Radix),senkyunolide M of phthalide compounds in Chuanxiong(Chuanxiong Rhizoma),beauvericin of amino acid compounds in Jiangcan(Bombyx Batryticatus),and inosine of nucleoside compounds in Dilong(Pheretima)were the main active molecular clusters of Naotaifang for antithrombotic effect.Conclusion The MCI-based similarity evaluation method established in this paper can scientifically screen the active ingredient clusters of TCM and compound prescriptions with high throughput,which complements the existing research methods such as network pharmacology,and also provides new ideas for the combination of Chinese and Western medicine.

关 键 词：定量构效关系法 分子连接性指数 相似度评价 脑泰方 抗脑血栓 分子对接 毛蕊异黄酮 洋川芎内酯 白僵菌素 肌苷 

分 类 号：R285[医药卫生—中药学]