基于网络药理学和分子对接技术的天麻-川芎药对治疗高血压作用机制研究

Study on the mechanism of Gastrodiae Rhizoma-Chuanxiong Rhizoma herb pair in the treatment of hypertension based on network pharmacology and molecular docking technology

借助网络药理学和分子对接探究天麻-川芎药对治疗高血压活性成分的靶点和作用机制。通过中药系统药理学数据库(TCMSP),限制口服生物利用度和类药性范围获取天麻、川芎两味药的活性成分及靶点。通过Drugbank和CTD筛选出疾病高血压靶点,借助韦恩图筛选出药对治疗疾病的共同潜在靶点;通过Cytoscape 3.2.1软件构建药对-疾病-成分-靶点的网络图,进一步用STRING数据库构建蛋白互作图,最后进行基因本体(GO)分析以及京都基因与基因组百科全书(KEGG)分析;应用Discovery Studio 4.5软件对活性成分与关键靶点进行分子对接验证。天麻-川芎药对共筛选出107个有效成分,对应1010个靶点;高血压对应得到2268个靶点;最终筛选出活性成分70个,共同靶点为83个;药对-疾病-成分-靶点调控网络包含155个节点,1217条边;GO分析,主要途径有血液循环,循环系统过程,核受体活性,转录因子活性等。KEGG分析,主要涉及神经活性配体-受体相互作用、Ca^(2+)信号通路、癌症的途径、cAMP信号通路等。分子对接显示,核心靶点与间羟基苯甲酸、油酸、亚油酸乙酯、反式β-金合欢烯和十四烷有较强的亲和力。天麻-川芎药对治疗高血压可能是通过TNF、PTGS2、EDN1等关键靶点发挥作用,同时通过调控神经活性配体-受体相互作用通路、Ca^(2+)信号通路、癌症的途径等多种通路发挥作用。初步揭示了天麻-川芎药对是通过多成分、多途径和多靶点协同治疗高血压的作用机制,为筛选治疗高血压的药物提供理论依据。

This study aims to explore the active components and pharmacological mechanisms of Gastrodiae Rhizoma-Chuanxiong Rhizoma in promoting blood circulation and removing blood stasis by the network pharmacology and molecular docking.The chemical constituents and target genes of Gastrodiae Rhizoma-Chuanxiong Rhizoma herb pairs were screened by the systematic pharmacological analysis platform(TCMSP).The potential active components of Gastrodiae Rhizoma-Chuanxiong Rhizoma herb pairs were screened under the conditions of bioavailability(OB)≥30%and drug-like(DL)≥0.18.The disease target of hypertension was searched through Drugbank and CTD,which was mapped with the potential target of herb pair,and the Wayne diagram was drawn.The target gene of the mapped active component was introduced into Cytoscape 3.2.1 to construct the drug pair-disease-component-target network map.The protein interaction map was constructed with string database,and go function analysis and KEGG pathway enrichment analysis were performed;the results of active components and key targets were verified the molecular docking by Discovery Studio 4.5 software.A total of 107 active ingredients and 1010 targets were screened for the Gastrodiae Rhizoma-Chuanxiong Rhizoma herb pair.Hypertension corresponds to 2268 targets.Through mapping,70 active ingredients and 83 intersection targets were selected.The traditional Chinese medicine-active components-target regulation network contains 155 nodes and 1217 edges.GO function enrichment results mainly involve the blood circulation,circulatory system process,nuclear receptor activity,transcription factor activity,and so on;KEGG enrichment results mainly involve the neuroactive ligand-receptor interaction,pathways in cancer,cAMP signaling pathway,calcium signaling pathway,and so on.The results of molecular docking showed that the core targets had strong affinity with m-hydroxybenzoic acid,oleic acid,mandenol,trans-β-farnesene and tetradecane.Gastrodiae Rhizoma-Chuanxiong Rhizoma herb pair may play a role in the treatment of hypertension through TNF,PTGS2,EDN1 and other key targets,and through the regulation of neuroactive ligand-receptor interaction,Ca^(2+) signaling pathway,in cancer pathways and other signal pathways.This study reveals the pharmacological mechanisms of Gastrodiae Rhizoma-Chuanxiong Rhizoma on multi-component,multi-channel and multi-target synergistic in the treatment of hypertension from the perspective of network pharmacology.