基于活性成分群的肠吸收转运机制多维解析黄芩道地药材的“质-效”本质

Genuineness is a unique, comprehensive standard, which is used to evaluate the quality of traditional Chinese medicines for thousands of years. The essence problem of the material basis of the geoherbs is the bottleneck problem and has restricted the development of geoherbs, therefore, a long-term and scientific development must involve a multidisciplinary cooperation. Based on the hypothesis that the core material basis of the geoherbs is the unique ratio between the components in TCMs , we will carry out multi-dimensional association studies, and build the evaluation system of quality and efficacy for the geoherbs from three respects, including active ingredients, intestinal absorption and efficacy . Therefore, Scutellariae Radix will be investigated as a representative object. Pharmacological indices closely related to traditional efficacy will be studied. Caco-2 cell models will be used to study the mechanism of intestinal absorption of the active ingredients in geoherbs and non-geoherbs. And then the research will gradually analyze the components in the aqueous extract of Scutellariae Radix by chromatography and mass spectrometry technologies and find these components with the largest contribution to efficacy and intestinal absorption. At the same time the components with different proportions will be screened by the response surface designs, and the optimal flavonoid components with the best efficacy will be restored, integrated, and verified. The purpose of this study is to provide experimental data to clarify the essential connotation of the material basis of the geoherbs on one hand, and to provide a new idea for researching the material basis of the geoherbs on the other hand.

道地性是千百年来人们评价中药品质的独特的、综合性的“金标准”。道地药材物质基础本质问题一直是制约道地药材发展的“瓶颈”问题。道地药材想要长远、科学的发展，必须开展多学科交叉和交流，基于“道地药材的核心物质基础是组分之间独特的比例”的假说，从“活性成分群—肠吸收转运—药效”开展多维关联性研究，构建道地药材的“质-效”评价体系。本研究以代表性道地药材黄芩为示范对象，选择体现黄芩传统功效的药理指标，结合Caco-2细胞模型研究道地与非道地药材中活性成分群的肠吸收转运机制，采用色谱和质谱技术，逐步解析黄芩水提物中对肠吸收转运和药效综合贡献度大的组分。同时借助效应面设计，对不同比例组分进行组合筛选，还原并整合出疗效最佳的“黄酮优化组分”，进行验证实验。本研究目的，一方面为阐明黄芩道地药材“质优效佳”的物质基础本质内涵提供依据，另一方面为道地药材物质基础研究提供新思路。

道地性是千百年来人们评价中药品质的独特的、综合性的“金标准”。基于“道地药材的核心物质基础是组分之间独特的比例”的假说，本项目从“活性成分群—肠吸收转运—药效”开展多维关联性研究，构建道地药材的“质-效”评价体系。成分定性定量研究表明，不同产地黄芩样品中化学成分在种类上没有差异，均含有25个黄酮化合物；但从黄酮类成分含量特征来看，道地产区黄芩中苷类成分含量较高，相应苷元类成分含量较低，其结构比特征（汉黄芩苷、黄芩素、汉黄芩素含量结构比均以黄芩苷含量为基准值1）不同于其他产地，为1∶0.224∶0.111∶0.013。大鼠离体肠外翻实验结果表明，不同产地黄芩提取物中黄芩苷和汉黄芩苷在同一肠段的吸收没有显著性差异；同样，按各产地的成分构成比得到的模拟黄酮组分样品中黄芩苷和汉黄芩苷在同一肠段的吸收也没有显著性差异。在体外抗炎实验中，不同产地黄芩提取物和相应的模拟黄酮组分均能有效抑制巨噬细胞释放NO。在对呼吸道合胞病毒（RSV）的抑制实验中，不同产地黄芩提取物和相应的模拟黄酮组分均能有效抑制RSV病毒活性，抗病毒活性的强弱与各黄酮含量不成正比，但与黄酮成分的结构比密切相关。道地产区（河北滦平）样品的抗RSV病毒作用最佳，治疗指数是5.2；基于道地产区黄芩中成分结构比1∶0.224∶0.111∶0.013模拟得到黄酮组分，也显示出优于其他7种结构比的抗RSV病毒活性。.综上所述，可发现黄芩苷、汉黄芩苷、黄芩素、汉黄芩素含量的高低与肠吸收程度强弱、抗炎活性高低、抗病毒活性高低的相关性不大。样品中黄酮类组分的构成比对其肠吸收程度、抗炎活性大小影响不大；但能显著影响样品的抗RSV病毒活性的强弱。该研究结果可为阐明黄芩传统功效的物质基础提供研究思路，为黄芩药材的质-效评价提供参考。