目的 比较解表功效中药化学和收涩功效中药成分的重要理化性质、Murcko骨架结构特征并计算Bayesian距离,为中药功效和化学成分结构性质的研究提供参考。方法 首先将《中药学》收载的解表中药和收涩中药名作为关键词,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)、中药化学数据库(Traditional Chinese Medicine Database,TCMD)3个数据库中进行检索,得到化学成分,查重合并后下载成分的2D结构文件。然后使用Discovery Studio 4.5计算分子的重要性质、统计参数|u|和Bayesian距离。当|u|>1.96时,认为解表中药的成分与收涩中药的成分之间存在显著性差异。使用KNIME 4.3.2软件CDK算法包完成化学成分的加氢、去除糖基等,使用RDKit算法包完成Murcko骨架计算。结果 解表中药成分与收涩中药成分在芳香环数量、分子环数、相对分子质量、氢受体数量、水溶解性、极性表面积、氢给体数量、细胞色素P450 2D6、血脑屏障、脂水分配系数、血浆蛋白结合预测分数等11个理化性质方面都存在明显差异。苯环、黄酮、环己烯、环己烷骨架在解表中药成分中占比大一些,而羽扇豆烷骨架、联苯环辛烯类木脂素骨架和异喹啉类生物碱骨架在收涩中药成分中占比大一些。从Bayesian距离来看,固精缩尿止带成分-固表止汗成分、固表止汗成分-敛肺涩肠成分的相对距离大于发散风寒成分-发散风热成分。结论 中药功效和化学成分性质结构之间存在内在联系。不同功效中药包含的化学成分在理化性质、高频Murcko骨架等方面都有明显差别。

Objective To provide a reference for the study of the efficacy and structural properties of chemical components of traditional Chinese medicine, the important physical and chemical properties, Murcko skeleton and the Bayesian distance of the chemical components of exterior-relieving herbs and apocrustic herbs were compared. Methods First of all, the chemical components were obtained and the plane structure documents after duplicate checking and merging were downloaded by searching the keywords of traditional Chinese medicine for exterior-relieving and apocrustic efficacy in TCMSP, ETCM, TCMD databases. Then, Discovery Studio4.5 was used to calculate the important characters and statistical parameters of molecule|u|. When|u|>1.96, it indicated a significant difference between the components of exterior-relieving herb and apocrustic herb. The CDK package of KNIME4.3.2 was adopted to complete the process of hydrogenation and glycosylation removal and the RDKit package was used to calculate the Murcko skeleton. Results The components of exterior-relieving herbs and apocrustic herbs were obviously different in 11 physical and chemical properties, including the number of the aromatic rings, the number of molecular rings, molecular weight, the number of hydrogen receptors, water-solubility, polar surface area, the number of hydrogen donors, cytochrome P450 2D6, blood-brain barrier, ALogP, and the predictive fraction of plasma protein binding. Benzene ring, flavonoids, cyclohexene, cyclohexane skeleton were accounted for a larger proportion in the components of exterior-relieving herbs, while lupine alkane, dibenzocyclooctadiene lignans, and isoquinoline alkaloid skeleton were accounted for a larger proportion in the components of the apocrustic herbs. According to the Bayesian distance, the relative distance between securing essence and reducing urination components-consolidating exterior and antiperspirant components, and consolidating exterior and antiperspirant components- constraining lung and astringing intestine components was greater than those between wind-cold dispersing components-wind-heat dispersing components. Conclusion There was an internal relationship between the efficacy and structural properties of chemical components of traditional Chinese medicine. There are obvious differences in physicochemical properties and high frequency Murcko skeleton in chemical components of TCM with different functions.

R284.1

中国中医科学院基本科研业务费自主选题项目（ZZ140304）