基于网络药理学和分子对接探讨太白楤木皂苷治疗缺血性脑卒中的药效物质及作用机制  

Material basis and mechanism of saponins from Aralia Taibaiensis for ischemic stroke by network pharmacology and molecular docking

作　　者：陶星茹 刘珂娣 赵石 李伟红 陈海霞 董泰玮 卫培峰[3] 段佳林 奚苗苗 TAO Xing-ru;LIU Ke-di;ZHAO Shi;LI Wei-hong;CHEN Hai-xia;DONG Tai-wei;WEI Pei-feng;DUAN Jia-lin;XI Miao-miao(College of Pharmacy,Shaanxi University of TCM,Xianyang Shaanxi 712046;Department of Pharmacy,Xijing Hospital,Air Force Military Medical University,Xi’an 710032;National Drug Clinical Trial Institute,the Second Affiliated Hospital,Shaanxi University of TCM,Xianyang Shaanxi 712000;Institute of Medicine,Northwestern Polytechnical University,Xi’an 710072;TANK Medicinal Biology Institute of Xi’an,Xi’an 710032)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046 [2]空军军医大学西京医院药剂科,西安710032 [3]陕西中医药大学第二附属医院国家药物临床试验机构,陕西咸阳712000 [4]西北工业大学医学研究院,西安710072 [5]西安天工生物医药研究所,西安710032

出　　处：《中南药学》2021年第11期2253-2262,共10页Central South Pharmacy

基　　金：国家自然科学基金(No.81470174,No.81903832);陕西中医药大学第二附属医院学科创新团队建设项目(No.2020XKTD-A04)。

摘　　要：目的基于网络药理学及分子对接初步探讨太白楤木皂苷(sAT)治疗缺血性脑卒中(IS)的药效物质及作用机制。方法通过文献收集sAT化学成分,并获取化学成分作用靶标;通过数据库获取IS疾病靶标,用Veen在线工具取交集,即sAT化学成分治疗IS靶标;利用Cytoscape 3.7.6软件中CytoHubba插件获得核心靶标;利用DAVID数据库进行GO及KEGG富集分析;利用AutoDock Vina软件对sAT化学成分与部分核心靶标进行分子对接验证;通过构建氧糖剥夺/复糖复氧(OGD/R)人脐静脉内皮细胞(HUVECs)模型,CCK-8法检测细胞活性,ELISA法检测VEGF水平,Western blot检测VEGF蛋白表达,对网络药理学及分子对接结果进行初步验证。结果共收集31种sAT化学成分,治疗IS靶标71个;GO功能和KEGG通路富集分析提示sAT化学成分治疗IS主要与血管内皮调节、细胞凋亡、炎症反应、钙离子通道生物过程有关;分子对接结果显示楤木皂苷D、去葡萄糖竹节参皂苷Ⅳa、竹节参皂苷Ⅰb能与部分核心靶标强烈结合;细胞实验结果表明,去葡萄糖竹节参皂苷Ⅳa显著提高HUVECs活性、促进VEGF释放、上调VEGF蛋白表达且呈剂量-效应依赖关系。结论sAT化学成分治疗IS呈多成分、多靶标、多通路协同作用特点,提示sAT可能通过促进血管新生,进而发挥脑保护作用,实验验证结果与网络药理学及分子对接预测结果一致,提示有效应用网络药理学及分子对接技术可为中药药效物质和作用机制研究提供依据。Objective To determine the material basis and molecular mechanism of saponins from Aralia Taibaiensis(sAT)for ischemic stroke(IS)based on network pharmacology and molecular docking technique.Methods Through literature search,we collected ingredients isolated from the sAT and obtained the targets of the ingredients.IS related targets were gained in the disease database.That was the common targets of the sAT and IS were obtained through the online tool Veen.The core targets were obtained with the CytoHubba plug-in in Cytoscape 3.7.6 software.DAVID database was used for GO enrichment analysis and KEGG pathway enrichment analysis.Besides,molecular docking of ingredients with some targets was verified by AutoDock Vina program.The oxygen and glucose deprivation/reperfusion(Oxygen and Glucose Deprivation/Reperfusion,OGD/R)human umbilical vein endothelial cell(human umbilical vein endothelial cells,HUVECs)models were replicated.The cell activity was detected by CCK-8 assay.The VEGF level was detected by ELISA.VEGF protein expression was detected by Western blot,and the network pharmacology and molecular docking results were preliminarily verified.Results Totally 31 ingredients and 71 overlapped genes related to IS and sAT were obtained.GO and KEGG enrichment analysis suggested that the treatment of IS was mainly related to such biological processes as vascular endothelial regulation,cell apoptosis,inflammatory response and calcium channels.The molecular docking showed that araloside D,deglucose-chikusetsu saponinⅣa and chikusetsu saponinⅠb were strongly combined with some of the core targets.Cell experiments showed that the deglucose-chikusetsu saponinⅣa significantly increased the HUVECs activity,promoted the release of VEGF,and up-regulated VEGF protein expression in a dose-dependent manner.Conclusion sAT shows a synergistic multi-molecular,multi-target and multi-pathway mechanism in the treatment of IS.The effective application of network pharmacology and molecular docking technology provide a basis for the stud

关 键 词：太白楤木皂苷 缺血性脑卒中 网络药理学 分子对接 血管新生 

分 类 号：R285[医药卫生—中药学]