摘要
目的龙江医派知名医家陈景河先生的益脑通络方在临床上治疗缺血性中风效果明显,但是其治疗机制方面的研究尚浅。文章基于中医药整合药理学研究平台(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,TCMIP)探讨益脑通络方治疗缺血性中风的分子机制。方法利用该平台筛选方剂的活性成分并预测其靶点;基于方剂靶点与疾病靶点的匹配结果筛选方剂-疾病的关键靶点,并对关键靶点进行基因本体论(gene ontology,GO)功能、生物过程(Reactome)富集分析;通过构建蛋白互作网络(protein-protein interaction network,PPI)、构建“中药-成分-靶点-通路”网络,分析并筛选益脑通络方治疗缺血性中风的主要活性成分和核心靶点;进一步对核心靶点与主要活性成分进行分子对接,以虚拟验证其结合能力并分析其结合模式。对核心活性成分和核心靶点进行分子对接验证。结果获得益脑通络方治疗缺血性中风的主要活性成分40种,关键靶点18个,包括了APP、PIK3CA等,GO功能分析主要富集在对凋亡的调控上,Reactome信号通路涉及了凋亡途径、炎症途径、基因调控、血管通路、神经再生、突触传导、细胞自噬等多途径。分子对接结果显示主要活性成分与核心靶蛋白具有结合力,川芎的萘呋内酯结合能力最强。结论益脑通络方中的萘呋内酯等多种活性成分能够作用于APP、PIK3CA等多靶点、通过促红细胞生成素(erythropietin,EPO)激活的PI3K等多通路,在缺血性中风中主要发挥抗凋亡等作用。
Objective CHEN Jinghe,a well-known physician of the Longjiang School of Medicine,has shown significant therapeutic effects on ischemic stroke in clinical practice with his Yinao Tongluo Formula(益脑通络方).However,the research on its therapeutic mechanism is still limited.The article explored the molecular mechanism of Yinao Tongluo Formulatreating ischemic strokebased onIntegrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP).Methods TCMIP was used to search the active components and predict the targets of the formula.Based on the matching results of potential targets of the formula and the targets of the disease,the key targets of the formula against the disease were screened,and gene ontology(GO)function enrichment and Reactome pathway enrichment analysis of the key targets were performed.The main components and core targets of Yinao Tongluo Formula against the ischemic stroke were analyzed and screened by constructing protein-protein interaction network(PPI)network and Chinese medicine-component-target-pathway network.Furthermore,it verified the molecular docking between the main active components and the core targets.Results There were 40 core components and 18 key targets for Yinao Tongluo Formula against the ischemic stroke,including APP,PIK3CA,etc.The results of GO functional enrichment mainly focused on regulating apoptosis.The results of Reactome pathway enrichment mainly involved apoptosis pathway,inflammatory pathway,gene regulation,vascular pathway,nerve regeneration,synaptic conduction,autophagy and others.The results of molecular docking showed that the active components had some binding ability,of which the naphthofurolactone in Chuanxiong(Chuanxiong Rhizoma)displayed the best.Conclusion The various active ingredients in Yinao Tongluo Formula,such as naphthofurolactone,can act on multiple targets such as APP and PIK3CA,and activate multiple pathways such as PI3K activated by erythropietin(EPO).They mainly play an anti apoptotic role in ischemic stroke.
作者
黄丽娜
杨毅
王博
李斌
蒋希成
HUANG Lina;YANG Yi;WANG Bo;LI Bin;JIANG Xicheng(Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang,China)
出处
《辽宁中医杂志》
CAS
北大核心
2024年第3期11-16,I0002,I0003,共8页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(82174261,81673865)
黑龙江省自然科学基金面上项目(LH2021H084)。
关键词
益脑通络方
缺血性中风
分子机制
整合药理学
Yinao Tongluo Formula(益脑通络方)
ischemic stroke
molecular mechanism
integrated pharmacology
