化学功效组学:中药现代研究的新方向——以止血药和活血化瘀药核心成分群研究为例

Chemical functiomics: a new direction for modern research on traditional Chinese medicine--a case study of core component group of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs

为了更好地解析中药化学成分与功效之间的复杂关系,该文首次提出“化学功效组学”(chemical functiomics)概念,通过止血药和活血化瘀药核心成分群的研究提出“化学功效组学”内涵和意义,为中药现代研究提供新方向。首先将《中药学》收载的止血药名和活血化瘀药名作为关键词,在中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)、中医药百科全书数据库(The Encyclopedia of Traditional Chinese Medicine, ETCM)、Natural Product Activity and Species Source Database(NPASS)3个数据库中进行检索得到化学成分。然后以MESH2021术语(中文版)为标准,规范止血药和活血化瘀药功效对应药理作用。最后使用Discovery Studio 4.5计算分子的ADMET(absorption、distribution、metabolism、excretion and toxicity)分子描述符,使用Origin 2021完成主成分分析和95%的置信椭圆计算,使用KNIME 4.3.2软件CDK算法和RDKit算法包完成化学成分的加氢和Murcko骨架计算。结果显示,止血药和活血化瘀药有404个共有成分,占总成分的17.3%。绘制止血药和活血化瘀药的化学功效图,可以看到药理作用组作为桥梁连接了功效组与化学成分组,药理作用的不同组合可以表达出不同的功效。止血药核心成分特有的Murcko骨架包括萘醌、四环三萜等,活血化瘀药核心成分特有Murcko骨架生物碱较多。该研究以止血药和活血化瘀药核心成分群的研究为例,为“化学功效组学”的研究提供了借鉴,也为中药功效物质基础研究提供支撑。

To analyze the complex relationship between chemical components and functions of traditional Chinese medicine, this study put forward the concept of "chemical functiomics" for the first time and defined the connotation and significance of "chemical functiomics" based on the research on the core components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs, which provided a new direction for modern research on traditional Chinese medicine. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Encyclopedia of Traditional Chinese Medicine(ETCM), and Natural Product Activity and Species Source Database(NPASS) were searched for the chemical components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs included in the Science of Chinese Materia Medica with the names of the above drugs as the key words. The pharmacological actions corresponding to the functions of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs were standardized with MESH2021 terms(Chinese version) as the standard. Discovery Studio 4.5 was used to calculate absorption, distribution, metabolism, excretion, and toxicity(ADMET) molecular descriptors. Principal component analysis and 95% confidence ellipse calculation were carried out using Origin 2021. Hydrogenation of chemical components and Murcko skeleton calculation were completed using the CDK algorithm and the RDKit algorithm packages in the KNIME 4.3.2. The results showed that there were 404 common components of hemostatic drugs and blood-activating/stasis-resolving drugs, accounting for 17.3% of the total components. The plotted chemical function diagrams of hemostatic drugs and blood-activating/stasis-resolving drugs showed that the pharmacological action group acting as a bridge connected the function group and the chemical composition group, and different combinations of pharmacological effects indicated different functions. The unique Murcko skeleton of the core components of hemostatic drugs mainly included naphthoquinone and tetracyclic triterpenes, while those of blood-activating/stasis-resolving drugs were mainly alkaloids. Based on the research on the core components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs, this study provides references for the study of "chemical functiomics" and support for the research on the functional material basis of traditional Chinese medicine.