摘要
目的通过网络药理学、分子对接和细胞验证,探讨化浊行血汤(HZXXD)治疗缺血性脑卒中的作用机制。方法运用TCMSP、TCMID、BATMAN-TCM数据库和文献检索筛选HZXXD的化学成分及靶点蛋白,在GeneCards和OMIM数据库获取缺血性脑卒中相关靶点,通过Cytoscape构建中药-活性成分-靶点网络图和蛋白相互作用网络图,再利用DAVID数据库对作用靶点进行基因组百科全书(KEGG)通路富集。采用Western blot法研究HZXXD对氧糖剥夺/复氧细胞模型炎症相关核心靶点表达的影响。最后利用Autodock将关键有效成分和重要靶点进行分子对接,评估其结合活性。结果筛选出76个活性成分,33个活性成分-疾病共有靶点。KEGG富集结果涉及肿瘤坏死因子(TNF)、化学致癌-活性氧、HIF-1等多条炎症相关信号通路。通过氧糖剥夺/复氧细胞实验发现TNF-α是HZXXD发挥作用的核心靶点。通过中药-活性成分-靶点网络图和分子对接筛选得到山柰酚、芹菜素、芦荟大黄素、黄芩素、豆甾醇5个与TNF-α结合力最强的化合物。结论HZXXD可能通过下调核心靶点TNF-α的表达从而治疗缺血性脑卒中,其活性成分可能为山柰酚、芹菜素、芦荟大黄素、黄芩素和豆甾醇。
Objective The mechanism of Huazhuo xingxue decoction(HZXXD)in the treatment of ischemic stroke was explored through network pharmacology,molecular docking and cell validation.Methods TCMSP,TCMID,BATMAN TCM database and literature search were used to get the chemical components and related target proteins of Huazhuo Xingxue Decoction,and the targets of dementia,stroke and amnesia were obtained from Genecards database and OMIM database.The traditional Chinese medicine-active components-target-network and protein interaction map were constructed by using Cytoscape,and the target was enriched by KEGG pathway by David database.Western blot was used to investigate the effect of HZXXD on inflammation-related core targets expression using oxygen and glucose deprivation/reoxygenation cell model.Finally,Autodock was used for molecular docking of key active ingredients and important targets to evaluate their binding activity.Results 76 active molecules and 33 common targets of herb-disease were screened out.KEGG bioaccumulation results involve multiple inflammatory signal pathways such as TNF,chemical carcinogenesis-reactive oxygen species and HIF-1.TNF-αwas found to be the core target of HZXXD by oxygen glucose deprivation/reoxygenation cell experiments.Five compounds with the strongest binding ability to TNF-α,kaempferol,apigenin,aloe-emodin,baicalein and stigasterol,were screened by traditional Chinese medicine-active ingredient-target network map and molecular docking.Conclusion Huazhuo Xingxue Decoction may down regulate the expression of core target TNF-α,kaempferol,apigenin,aloe emodin,baicalein and stigasterol may be the main active substances for TNF-αbinding.
作者
陈萌
杜玥瑾
郭春莉
王娜娜
侯非
张雨辰
刁子朋
郑娟尔
付强
CHEN Meng;DU Yuejin;GUO Chunli;WANG Nana;HOU Fei;ZHANG Yuchen;DIAO Zipeng;ZHENG Juaner;FU Qiang(China National Institute of Standardization,Beijing 100191,China;Affiliated Hospital of Shandong Second Medical University,Weifang 261000,China;Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)
出处
《世界科学技术-中医药现代化》
北大核心
2025年第5期1461-1470,共10页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
中国中医科学院科技创新工程大攻关项目(CT2021A01303):脑卒中高危人群“血浊”证及化浊行中方干预方案研究,负责人:郭春莉
国家市场监督管理总局科技计划项目(2024MK203,602024Y-11434):防控未成年人短视频沉迷的服务设计关键技术及标准研究,负责人:郑娟尔。
关键词
化浊行血汤
缺血性脑卒中
网络药理学
分子对接
氧糖剥夺/复氧细胞模型
TNF-α
Huazhuo Xingxue Decoction
Ischemic stroke
Network pharmacology
Molecular docking
Oxygen glucose deprivation/reoxygenation cell model
TNF-α
