基于分子拓扑指数的中药宏观质量新模式研究

Quality of traditional Chinese medicine is the lifeline of clinical safety and therapeutic effect. At present, there are mainly two basic models of chemical composition and biological effect, which have both advantages and disadvantages, where lack a bridge to link both. However, there still demands a new model that can integrate the two models perfectly and characterize the macroscopic quality, which remains a breakthrough. The team found that "the total amount average first order MCI of all components in Houttuynia cordata thumb (HCT) is stable", when we studied the relationship between Chinese medicine quality and supramolecular chemistry. Therefore, the hypothesis is proposed that molecular topological index is a bridge between chemical components and biological effects of TCM, and its related topological index can scientifically characterize the macroscopic TCM. For this program HCT will be used as a model Chinese medicine, the structural formula and peak area of each component responded in GC-MS analysis will be obtained from 3 habitats 15 batches of HCT, and then one kinds of topological index series (molecular connectivity index) will be obtained by using AM1 algorithm. Then will study the correlation between the topological index and the bacteriostatic activity of HCT volatile oil, and the topological index related to the antibacterial activity will be screened by principal component analysis. The statistics (parameters) which can characterize the macroscopic quality of HCT will be obtained by regression analysis. This project will provide a novel idea and method for the study of macroscopic quality of Chinese medicine to impel TCM quality research.

中药质量是攸关临床安全性与疗效的生命线，其研究现主要以化学成分和生物效应两种模式为主，各有长短，但仍缺乏贯穿两者的桥梁，以整体表征中药宏观质量。本团队在中药质量与超分子化学研究中发现“单味中药总响应成分的总量平均一阶分子连接性指数趋向稳定”现象，故提出“分子拓扑指数是连接化学成分与生物效应的桥梁，其相关拓扑指数的统计量能科学表征中药宏观质量”假说。本研究以鱼腥草为模型药，首先开展3产地15批次鱼腥草总挥发油气质联用分析，获得每个响应成分的分子式与峰面积；然后利用AM1算法获得1类拓扑指数系列（分子连接性指数）；再用主成分分析展开拓扑指数与鱼腥草挥发油抑菌活性相关性研究，筛选出与抑菌活性相关性优的拓扑指数系列；作统计与回归分析，得出能定性定量表征鱼腥草宏观质量的统计量，最终获得一种中药宏观质量研究新模式，推进了中药质量的研究进程。

项目实施期间，本研究获得了不同产地不同采收时期的30批鱼腥草总挥发油、GC-MS指纹图谱、挥发性成分分子式及相对含量；应用总量统计矩法计算出指纹图谱总量零阶矩（AUCT）、总量一阶矩（MCRT）及总量二阶矩（VCRT）等一系列总量统计矩参数；使用程序软件计算得到3类拓扑指数系列：分子连接性指数（MCI）、分子形状属性（MSI）指数及电性拓扑状态（E-State）指数值；进行体外抑菌实验，获得30批鱼腥草挥发油对金黄色葡萄球菌、大肠杆菌的抑菌圈值和最小抑菌浓度值（MIC），及与抑菌圈大小呈正相关和负相关的组分、及其相对含量；以峰高、峰面积、各项拓扑指数作为参数进行主成分分析，得出各批鱼腥草挥发油的特征峰；对比不同拓扑指数下的特征峰对应化合物，与相应的同抑菌圈大小呈正或负相关组分对应的化合物并行比较，得出能表征抑菌活性相关的拓扑指数。最终得到能定性定量表征鱼腥草宏观质量的参数。本研究开创了一种中药宏观质量的定性定量表征新思路与新方法；培养了博士研究生1名，硕士生3名。在国内外发表学术论文19篇，其中 SCI 收录 1 篇、CSCD核心10篇、CSCD扩展6篇、其他2篇；进行专题报告2次。期间项目组获得湖南省中医药学会一等奖1项、中华中医药学会三等奖1项、湖南省自然科学一等奖1项。