基于专利网的中药治疗偏头痛方剂核心药物 配伍规律及分子作用机制研究

Analysis of core medication rules and molecular mechanism of traditional Chinese medicine formula in the treatment of migraine according to patent information search platform

[目的]应用数据挖掘分析中药专利治疗偏头痛的组方规律,从“疾病-药物-化学成分-关键靶点-功能分析”角度,分析中药治疗偏头痛的核心药物配伍规律及潜在的分子作用机制,为临床用药提供依据。[方法]筛选中药专利治疗偏头痛的有效方剂,统计中药使用频次、四气五味、归经、功效和功效分类频次;对有效方药进行关联规则分析及系统聚类统计。筛选预测得到的高频方剂的有效成分,构建药物-疾病交际靶点,构建药物-成分-靶点网络图及蛋白互作网络图,进行GO功能和京都基因和基因组百科全书(KEGG)通路富集分析。[结果]共纳入512个中药处方,6148味中药,使用频数>40次的有34味,药性以温、平为主,药味以辛、甘为主,归经以肝、肺、脾经为主,分类以祛风止痛为首。关联规则统计21条药对,主要以行气活血,祛风止痛,清利头目功效的药对为主。聚类分析4类,其中由菊花、蔓荆子、川芎、白芷、防风、羌活、细辛、薄荷聚类组成的药物处方为高频药物组方,可用以治疗风热型偏头痛。白细胞介素(IL)-1B,血管内皮生长因子A(VEGFA)、前列素内环氧化物合酶2(PTGS2)、肿瘤坏死因子(TNF)、表皮生长因子受体(EGFR)、IL-6、丝裂原活化蛋白激酶3(MAPK3)可能为该方剂治疗偏头痛的关键靶点,MAPK信号通路在核心靶点、功能富集及通路富集中均有显示,可能为该方剂治疗风热型偏头痛的关键通路。[结论]临床治疗偏头痛以行气活血,祛风止痛,清利头目功效药物为主,新的高频药物组方可治疗风热所致的偏头痛,MAPK信号通路可能为其关键信号通路。

[Objective]To apply data mining to analyze the composition rules of Chinese medicine patent in the treatment of migraine,from the perspective of“disease-drug-chemical components-key target-function analysis”,to analyze the core drug compatibility rules and potential molecular mechanisms of traditional Chinese medicine(TCM)in the treatment of migraine,in order to provide the basis for clinical medication.[Methods]Screening effective information of TCM patent in the treatment of migraine,counting the frequency of traditional Chinese medicine,four qi and five flavors,meridian and efficacy classification frequency,analyze the association rules of effective prescriptions,cluster the Chinese drugs.The active ingredients of the predicted high-frequency prescriptions were screened,and the drug-disease interaction targets were constructed.The drug-ingredient-target network diagram and the protein interaction network diagram were constructed and GO functional and KEGG pathway enrichment analysis were analyzed.[Results]A total of 512 prescriptions were included,including 6148 herbs,34 herbs with frequency>40 times.The medicinal properties were mainly warm,flat,and the flavors were mainly pungent,sweet.The meridian distribution were mainly liver,lung and spleen meridians,and the classification was given priority to dispelling wind and relieving pain.Association rules showed 21 drug groups,cluster analysis showed 4 categories.The new drug prescription composed of Dendranthema morifolium,Vitex trifolia L.,Ligusticum chuanxiong hort,Angelica dahurica,Radix saposhnikoviae,Notopterygium incisum,Asarum sieboldii Miq.andMentha piperitawhich were the high-frequency drugs.IL-1B,VEGFA,PTGS2,TNF,EGFR,IL-6,and MAPK3 may be the key targets in the treatment of migraine with this prescription.The MAPK signaling pathway has been shown in the core targets,functional enrichment and pathway enrichment,which may be the key pathway for the prescription to treat wind-heat migraine.[Conclusion]The clinical treatment of migraine mainly focuses on activating qi and promoting blood circulation,expelling wind and relieving pain,and clearing the head.The new high-frequency prescription may treat the migraine caused by wind-heat via the key signal pathway that is MAPK signal pathway.