摘要
目的采用网络药理学方法对川芎治疗偏头痛的机制进行分析,为深入研究川芎在治疗偏头痛方面的作用机制奠定基础。方法通过中药系统药理学数据与分析平台(TCMSP)平台筛选结合文献检索获得川芎的化学成分和作用靶点,并通过SWISSTARGET数据库筛选和预测作用靶点。通过Genecards、DrugBank等数据库筛选出治疗偏头痛的靶标。取药物疾病交集基因通过软件Cytoscape 3.8.0构建药物—有效成分—疾病靶点网络并筛选关键药效分子及药物核心靶点。基于STRING数据库构建PPI蛋白互作网络,通过cytoNCA插件筛选PPI核心靶点。通过DAVID生物信息学资源数据库对药物核心靶点及PPI核心靶点进行GO功能富集分析,运用KOBAS 3.0对药物核心靶点及PPI核心靶点进行KEGG子通路富集分析。将关键药效分子与对应的度值较高的药物核心靶点及PPI核心靶点进行分子对接验证药物分子与靶点作用情况,选择评分较高的结果进行可视化。结果网络中包含Myricanone(杨梅酮)、Mandenol(亚麻油酸乙酯)等11个化合物,作用于169个作用靶点。生物学过程GO功能富集分析得到997个GO条目(P<0.01),KEGG通路富集得到76条信号通路(P<0.01),主要涉及循环系统血管过程、血管管径调节、胞内钙离子浓度调节、细胞内钙离子稳态、肽基-酪氨酸磷酸化、5-HT受体活性等生物过程及信号通路。分子对接结果显示Mandenol、Wallichilide、Senkyunone是关键药效分子中的核心成分,环加氧酶2(PTGS 2)与丝裂原激活蛋白激酶14(MAPK 14)是川芎治疗偏头痛较为关键的靶点蛋白。最后通过动物实验及指标检测对关键药效分子中的Mandenol对涉及的主要生物过程作用进行初步验证,结果Mandenol可以显著降低偏头痛大鼠血清中NO水平及iNOS活性(P<0.05),从而进一步影响循环系统血管过程及血管管管径调节过程。结论该研究初步揭示了川芎通过多成分多靶点多通路治疗偏头痛的作用机制,川芎可能主要通过循环系统血管过程、血管管径调节等过程发挥其活血化瘀功效来改善和治疗偏头痛。
Objective To investigate the mechanism of Chuanxiong Rhizoma in the treatment of migraine based on network pharmacology and molecular docking to provide references for further research.Methods The chemical constituents and action targets of Chuanxiong Rhizoma were obtained by TCMSP combined with literature retrieval,and the action targets were screened out and predicted by SwissTarget.The targets against migraine were selected from GeneCards and DrugBank.Cytoscape 3.8.0 was used to construct a drug-active component-disease target network based on the drug-disease common genes,and the key active molecules and drug core targets were screened out.The protein-protein interaction(PPI)network was constructed using STRING,and core PPI targets were screened out by the CytoNCA plug-in.Drug core targets and PPI core targets underwent GO function enrichment analysis and KEGG subpathway enrichment analysis by DAVID and KOBAS 3.0,respectively.The interaction of drug molecules and targets was verified by molecular docking of key active molecules with corresponding drug core targets and PPI core targets with higher degree values,and the results with higher scores were selected for visualization.Results There were 11 compounds including myricanone and mandenolin the disease-target network,acting on 169 targets.GO function enrichment analysis obtained 997 GO entries(P<0.01),and KEGG pathway enrichment analysis obtained 76 signaling pathways(P<0.01),mainly involving vascular processes in the circulatory system,vascular diameter regulation,intracellular calcium concentration regulation,intracellular calcium homeostasis,peptidyl-tyrosine phosphorylation,5-HT receptor activity,and other biological processes and signaling pathways.The results of molecular docking showed that mandenol,wallichilide,and senkyunone were the core components of the key active molecules,and PTGS2 and MAPK14 were the key target proteins of Chuanxiong Rhizoma in the treatment of migraine.As revealed by animal experiments and index detection,the effect of mandenol in the key active molecules on the main biological processes involved was preliminarily verified.The results showed that mandenol could significantly reduce the serum NO level and blunt iNOS activity in migraine rats(P<0.05),thereby further affecting the vascular processes in the circulatory system and the process of vascular diameter regulation.Conclusion This study preliminarily revealed the mechanism of Chuanxiong Rhizoma in the treatment of migraine through multiple components,targets,and pathways.Chuanxiong Rhizoma may be effective in promoting blood circulation and removing blood stasis through the vascular processes in the circulatory system and the regulation of vascular diameter to treat migraine.
作者
王玉瑶
王青
刘美斯
左阳
王力苇
赵仕博
石博文
赵永烈
WANG Yu-yao;WANG Qing;LIU Mei-si;ZUO Yang;WANG Li-wei;ZHAO Shi-bo;SHI Bowen;ZHAO Yong-lie(Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029;Beijing University of Chinese Medicine,Beijing 100029)
出处
《世界中西医结合杂志》
2022年第6期1133-1142,共10页
World Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金项目(81873256)。
关键词
川芎
偏头痛
网络药理学
分子对接
Chuanxiong Rhizoma
Migraine
Network Pharmacology
Molecular Docking
