气滞胃痛颗粒中白芍抗炎镇痛作用的构效组学

Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Paeoniae Radix Alba in Qizhi Weitong Granules

摘要:

目的 采用构效组学的研究方法，阐释白芍总苷发挥抗炎镇痛作用的药效物质。方法 在课题组前期体外药效筛选的基础上，采用甲醛致小鼠足肿胀模型，开展白芍总苷体内抗炎镇痛药效研究；运用中药系统药理数据库和分析平台（TCMSP），在线人类孟德尔遗传数据库（OMIM），检索互作基因（STRING）等网络数据库，获取并筛选白芍抗炎镇痛活性成分的核心靶点；采用计算机虚拟筛选技术将不同类型的白芍总苷与核心靶点进行对接，以各靶点与活性结构的综合评分总分为遴选原则，得到高结合活性的关键核心靶点，以靶点为桥梁，将白芍中一类或多类化学成分结构与药效紧密关联，通过白芍总苷各类结构与药效靶点结合规律，探讨分析构效关系。结果 白芍总苷在体内具有良好的抗炎镇痛药效，筛选得到23个白芍活性成分，其发挥抗炎镇痛作用的核心靶点为表皮生长因子受体（EGFR），信号传导及转录激活因子3（STAT3），血管内皮生长因子A（VEGFA），细胞肿瘤抗原p53（TP53），原癌基因转录因子（JUN）；按照母核进行结构归类，其中蒎烷单萜苷类成分16个，蒎烯单萜苷类成分4个，单萜内酯苷类成分2个，单萜酮类成分1个；经对接评分筛选得到关键核心靶点为EGFR、STAT3；通过活性结构与关键核心靶点的构效分析发现，母核上的酮基及苯环上基团的引入，会对结合活性造成影响。结论 该研究基于白芍总苷抗炎镇痛的药效作用，采用构效组学研究方法，可以分析白芍总苷抗炎镇痛的物质基础，为中药药效物质的阐释提供新思路新方法。

Abstract:

Objective To elucidate the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba from structure-activity omics.Method On the basis of the previous in vitro efficacy study by our research group， a mouse model of foot swelling was induced by methyl aldehyde and used to study the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba in vivo. The core targets of the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. Molecular docking was conducted for the total glucosides of Paeoniae Radix Alba with the core targets， and the key core targets with high binding affinity were screened out according to the comprehensive score of each target and active structure. The structure-activity relationship was analyzed with targets as a bridge through the combination of compound structures and pharmacological effects.Result The total glucosides of Paeoniae Radix Alba had good anti-inflammatory and analgesic effects in vivo. The core targets of 23 active components of Paeoniae Radix Alba were epidermal growth factor receptor （EGFR）， signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， cellular tumor antigen p53 （TP53）， and proto-oncogene transcription factor （JUN）. According to the structure of the parent nucleus， there were 16 pinane monoterpene glycosides， 4 pinene monoterpene glycosides， 2 monoterpene lactone glycosides， and 1 monoterpene ketone. The key core targets screened out by molecular docking were EGFR and STAT3. The structure-activity analysis of the active compound structures and the key core targets showed that the introduction of ketone group and benzene ring group on the parent nucleus affected the binding activity.Conclusion This study analyzed the material basis for the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba from structure-activity omics， providing new ideas and methods for revealing the pharmacodynamic substances in traditional Chinese medicine.