基于计算机模拟技术探讨当归活血和止痛作用的活性成分及其关联性  

Study on the Active Components of Angelica Sinensis in Promoting Blood Circulation and Relieving Pain,and Their Correlation Based on Computer Simulation Technology

作　　者：郑春松 段辛威 王圣杰 朱晓勤 付长龙 叶蕻芝 ZHENG Chunsong;DUAN Xinwei;WANG Shengjie;ZHU Xiaoqin;FU Changlong;YE Hongzhi(Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350122,China;Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fuzhou,Fujian 350122,China)

机构地区：[1]福建中医药大学中西医结合研究院,福建福州350122 [2]福建省中西医结合老年性疾病重点实验室,福建福州350122

出　　处：《福建中医药》2021年第8期1-4,13,共5页Fujian Journal of Traditional Chinese Medicine

基　　金：福建省自然科学基金项目(2019J01354)。

摘　　要：目的采用计算机模拟技术,从活性成分的角度探讨当归活血和止痛作用及其关联性。方法①从中药系统药理学数据库及分析平台(TCMSP)中,检索当归的化学成分125个,以凝血酶(Thrombin)、血栓素A2受体(TXA2R)、纤溶酶原激活物抑制物1型(PAI-1)、凝血因子Ⅸa(FactorⅨa)为活血功效的靶点,以p38、肿瘤坏死因子α(TNF-α)、诱导型一氧化氮合酶(iNOS)、磷酸二酯酶4A(PDE4A)为止痛功效的靶点,在蛋白质数据库(RCSB PDB)中下载有配体结合的蛋白复合物结构,代码分别为1AWH、6IIV、7AQF、3LC3、1OUY、2AZ5、4NOS和3TVX;利用分子对接技术,筛选大于蛋白复合物结构中的原配体的DOCK-SCORE高的化合物,视为当归中活血功效和止痛功效的活性成分。②构建当归活血功效和止痛功效的活性成分数据集,提取其全局指纹,计算其Tanimoto相似系数来反映两活性成分数据集的化学结构特征相似度。当相似系数值为0时,表示两数据集间没有相同的分子结构片段;当系数为1时,则表示有相同的字节编码,也就表示有相同的分子结构片断,即系数越接近1,代表两数据集在分子结构特征方面的关联性越好。③利用Cytoscape生物网络平台,构建当归活性成分与功效靶点相互作用的可视化网络,选择度值≥3的节点,视为网络中的重要活性成分和靶点。结果①从当归化学成分中筛选出8个活血功效的活性成分和17个止痛功效的活性成分,其中,活血和止痛功效的共同活性成分有6个,主要属于苯肽类、磷酯类、生物碱类、有机酸类等,75%的活血功效的成分具有止痛作用,但仅约35%的止痛功效的成分具有活血作用。②当归活血和止痛功效活性成分数据集全局指纹的Tanimoto相似系数为0.7736,显示两个功效活性成分之间在结构特征上具有很好的关联性。③当归活性成分-靶点网络显示了活性成分与功效靶点之间存在“一对多,多对一”的特Objective:To explore the functions of promoting blood circulation and relieving pain in Angelica sinensis and their correlation from the perspective of active components based on computer simulation technology.Methods:(1)125 chemical components of Angelica sinensis were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).Thrombin,thromboxane A2 receptor(TXA2R),plasminogen activator inhibitor type 1(PAI-1)and factor Ⅸ a were used as the targets of promoting blood circulation,and p38,tumor necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS)and phosphodiesterase 4A(PDE4A)were used as the targets of relieving pain.Their protein complex structures containing respective ligand were downloaded from the protein database(RCSB PDB),and the PDB identifications were 1AWH,6IIV,7AQF,3LC3,1OUY,2AZ5,4NOS and 3TVX,respectively.Molecular docking technology was used to screen active compounds with larger dock-score than the original ligand in the respective protein complex structure,which were regarded as the active components with promoting blood circulation and relieving pain in Angelica sinensis.(2)The active component datasets of Angelica sinensis for promoting blood circulation and relieving pain were constructed.Tanimoto similarity coefficient was calculated to reflect the similarity of chemical structure characteristics of the two molecular datasets after extracting their global fingerprints.When the similarity coefficient is 0,it means that there is no same molecular structure fragment between the two datasets;when the coefficient is 1,it means that there are the same byte codes,in other words,there are the same molecular structure fragments between the two datasets.Furthermore,the coefficient is closer to 1,the correlation between the two data sets is better in terms of molecular structure characteristics.(3)The visual networks of the interaction between active components and efficacy targets of Angelica sinensis were constructed by the biological network pl

关 键 词：当归 活血功效 止痛功效 活性成分 计算机模拟 

分 类 号：R285.5[医药卫生—中药学]