目的基于超分子“印迹模板”理论,首创因子旋转法与分子连接性指数(molecular connectivity index,MCI)耦合策略,系统解析活血化瘀中药的共性物质基础及其“结构-功能”关联机制,为中药质量标志物(quality markers,Q-Marker)筛选提供新...目的基于超分子“印迹模板”理论,首创因子旋转法与分子连接性指数(molecular connectivity index,MCI)耦合策略,系统解析活血化瘀中药的共性物质基础及其“结构-功能”关联机制,为中药质量标志物(quality markers,Q-Marker)筛选提供新范式。方法采用UPLC法建立13味活血化瘀中药(川芎、丹参、桃仁、马鞭草、红花、延胡索、月季花、牛膝、益母草、三七、白芍、赤芍、当归)及3种经典复方(补阳还五汤、桃红四物汤、血府逐瘀汤)的指纹图谱,通过匹配频数法划分26个“印迹模板”成分簇作为结构性“物质单元”;利用因子旋转法对成分簇进行降维整合,提取6个功能性“物质单元”(累积方差贡献率88.37%),结合归一化评分评估给药性“物质单元”的综合效应;借助中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)数据库计算MCI,量化成分簇结构相似性,并通过急性血瘀大鼠模型验证核心成分的药效贡献。结果发现活血化瘀中药的“印迹模板”成分簇可划分为6个功能性“物质单元”,其中前3个功能性“物质单元”(累积贡献率66.85%)以黄酮类、生物碱类及萜类为核心,主导活血化瘀效应;补阳还五汤因黄酮类、生物碱类及萜类的高丰度匹配,综合评分(2.44)显著优于其他方剂,证实其“印迹模板”与靶点空间结构的最佳适配性;黄酮类、萜类、生物碱类的MCI相似度达0.9887、0.9701、0.9407,且10个对照品与中药群体的一阶矩RSD仅1.794%,验证其“印迹模板”特征;动物实验证实,功能性“物质单元”可显著改善急性血瘀大鼠血液流变学指标(低切与中切全血黏度均显著降低,P<0.01)及凝血功能[活化部分凝血酶原时间(activated partial thromboplastin time,APTT)显著延长,P<0.01]。综合评分最高的给药性“物质单元”来源方剂(补阳还五汤组)在改善血液流变学及凝血功能的多个方面,效果均优于评分最低的来源(白芍组),体现多成分协同增效特性。结论首次构建“个体-结构-功能-给药”四维解析体系,揭示黄酮类、生物碱类及萜类成分,通过超分子“印迹模板”动态识别机制,介导活血化瘀效应的核心途径。该研究为中药复杂体系的质量评价与作用模式解析提供了量化工具,推动中药现代化研究从“单一成分”向“结构簇协同”范式转变。展开更多
Molecular imprinting has become a powerful method for the preparation of robust materials that have the ability to recognize a specific chemical species. The stability,ease of preparation and low cost of these materia...Molecular imprinting has become a powerful method for the preparation of robust materials that have the ability to recognize a specific chemical species. The stability,ease of preparation and low cost of these materials have led to their assessment as substitutes for antibodies or enzymes in chemical sensors,catalysis and separations. The present techniques used to prepare molecular imprinting materials most often result in materials exhibiting a high affinity and selectivity but low capacity and poor site accessibility of the target molecules. In this study,we report a simple procedure for applying molecular imprinting functional groups to the inner surfaces of the AAO template-synthesized sol-gel nanotubes for biochemical separation of estrone. Using of nanotubes as the imprinted materials has the advantage of high affinity,selectivity,capacity and site accessibility for the target molecules. And it is important to emphasize that template route can be used to prepare imprinted nanotubes of nearly any materials. [WT5HZ]展开更多
文摘目的基于超分子“印迹模板”理论,首创因子旋转法与分子连接性指数(molecular connectivity index,MCI)耦合策略,系统解析活血化瘀中药的共性物质基础及其“结构-功能”关联机制,为中药质量标志物(quality markers,Q-Marker)筛选提供新范式。方法采用UPLC法建立13味活血化瘀中药(川芎、丹参、桃仁、马鞭草、红花、延胡索、月季花、牛膝、益母草、三七、白芍、赤芍、当归)及3种经典复方(补阳还五汤、桃红四物汤、血府逐瘀汤)的指纹图谱,通过匹配频数法划分26个“印迹模板”成分簇作为结构性“物质单元”;利用因子旋转法对成分簇进行降维整合,提取6个功能性“物质单元”(累积方差贡献率88.37%),结合归一化评分评估给药性“物质单元”的综合效应;借助中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)数据库计算MCI,量化成分簇结构相似性,并通过急性血瘀大鼠模型验证核心成分的药效贡献。结果发现活血化瘀中药的“印迹模板”成分簇可划分为6个功能性“物质单元”,其中前3个功能性“物质单元”(累积贡献率66.85%)以黄酮类、生物碱类及萜类为核心,主导活血化瘀效应;补阳还五汤因黄酮类、生物碱类及萜类的高丰度匹配,综合评分(2.44)显著优于其他方剂,证实其“印迹模板”与靶点空间结构的最佳适配性;黄酮类、萜类、生物碱类的MCI相似度达0.9887、0.9701、0.9407,且10个对照品与中药群体的一阶矩RSD仅1.794%,验证其“印迹模板”特征;动物实验证实,功能性“物质单元”可显著改善急性血瘀大鼠血液流变学指标(低切与中切全血黏度均显著降低,P<0.01)及凝血功能[活化部分凝血酶原时间(activated partial thromboplastin time,APTT)显著延长,P<0.01]。综合评分最高的给药性“物质单元”来源方剂(补阳还五汤组)在改善血液流变学及凝血功能的多个方面,效果均优于评分最低的来源(白芍组),体现多成分协同增效特性。结论首次构建“个体-结构-功能-给药”四维解析体系,揭示黄酮类、生物碱类及萜类成分,通过超分子“印迹模板”动态识别机制,介导活血化瘀效应的核心途径。该研究为中药复杂体系的质量评价与作用模式解析提供了量化工具,推动中药现代化研究从“单一成分”向“结构簇协同”范式转变。
文摘Molecular imprinting has become a powerful method for the preparation of robust materials that have the ability to recognize a specific chemical species. The stability,ease of preparation and low cost of these materials have led to their assessment as substitutes for antibodies or enzymes in chemical sensors,catalysis and separations. The present techniques used to prepare molecular imprinting materials most often result in materials exhibiting a high affinity and selectivity but low capacity and poor site accessibility of the target molecules. In this study,we report a simple procedure for applying molecular imprinting functional groups to the inner surfaces of the AAO template-synthesized sol-gel nanotubes for biochemical separation of estrone. Using of nanotubes as the imprinted materials has the advantage of high affinity,selectivity,capacity and site accessibility for the target molecules. And it is important to emphasize that template route can be used to prepare imprinted nanotubes of nearly any materials. [WT5HZ]
