基于"QCAR/3D-QSAR"的甘草抗HBV肝损伤多靶导向作用研究

乙型肝炎（HBV）肝损伤是目前仍未解决的世界性复杂慢性疾病。前期课题组开展了甘草化学成分及活性研究，并依据中药药效作用特点及相关文献报道，提出甘草抗HBV肝损伤活性是其三萜皂苷类成分"多靶点-低亲和"协同作用的结果；成分对靶点的亲和，以及靶点之间的影响呈现非线性对应关系。.针对以上科学问题，本课题拟以甘草三萜皂苷类成分/多组分-效应评价为实验体系，通过多重色谱分离技术定向分离甘草三萜皂苷，并以多个关键靶点（NA、HMGB-1及 PLA 2）的活性评价结合"QCAR/3D-QSAR"模拟计算技术，分别建立多组分与效应之间的人工神经网络模型和结构与靶点之间的C0MFA模型，阐释甘草抗HBV肝损伤"多靶点-低亲和"的协同对应关系，筛选高效低毒的活性化合物/组合物，为中药药效物质基础及活性筛选提供新的研究思路，并对中药新药的创制具有启迪和借鉴意义。

Hepatic damage induced by HBV is a complex and chronic disease around the world. Based on our priliminary experiments on chemical constituents and hepatoprotective effect of licorice, a hypothesis has been put forward that the hepatoprotective effect of licorice were result of licorice triterpene saponins via integration and synergistic action of "multicomponent, multitarget and lowaffinity". .This work will focus on screening and isolation of active ingredients of licorice for multitargeted hepatoprotective action involving single or multicomponent with the use of biological evaluation on target cells and several key target proteins (NA, HMGB-1 and PLA 2), quantitative composition activity relationship (QCAR) analysis and three dimensional quantitative structure activity relationship (3D-QSAR) analysis. It would be expected to set up artificial neural network model and C0MFA model for prediction of nonlinear dynamic relationship between compounds /multicomponent and bioactivity. Meanwhile this research would reveal the the hepatoprotective effect of licorice via synergistic action of "multicomponent, multitarget and lowaffinity" and find out high bioactive and low toxcity compounds /multi-component. To sum up, this work will provide us with a good method of screening and analyzing of the bioactive components in CMM and help to open up new areas of exploration for the creation of new drugs that could be use as a form of CMM.