基于植物脂质组学的多基原中药海藻的鉴定研究

中药海藻为褐藻门马尾藻属羊栖菜和海蒿子的干燥藻体，是中国药典收载的两种海洋植物类中药材之一。市售海藻普遍存在混伪品，基本为马尾藻属植物数种混杂，传统鉴定很难区分物种；药典法测定岩藻糖计的多糖含量，与另一药典品种昆布方法相同。本项目旨在发现质量标志物，建立鉴别海藻真伪优劣的理化方法。项目组前期发现海藻脂质是其主要药效成分，脂肪酸、植物甾醇、甘油糖脂、萜类等不同结构类型的多个脂质分子，共同作用于核受体家族LXRs、PPARs、PXR等多个靶点发挥药效。本项目在前期基础上，运用植物脂质组学技术，采用色谱-串联质谱分析脂质多维轮廓谱，区分物种，发现化学分类标志物；以核受体为靶点，虚拟筛选并验证活性，建立马尾藻脂质数据库，从“化学网络-生物网络”发现药效指标成分。整合化学分类标志物和药效指标成分，提炼出质量标志物，建立海藻理化鉴定方法，保障临床用药安全有效，推动我国蓝色药库建设。

Traditional Chinese medicine SARGASSUM (PinYin: HAI ZAO), are originated from dried frond of Sargassum fusiforme and Sargassum pallidum according to the Chinese Pharmacopoeia. In the commercial materia medica SARGASSUM, it is common to see mixtures of several spices from Sargassum genus. Morphological and DNA barcoding could not solve all the problems in quality control. The aim of this project is to discover Q-markers and establish a chemical identifying method. Our previous studies found that lipids are the main effective components in SARGASSUM, which fatty acids, phytosterols, glycoglycerolipids, terpenoids are the main lipid types, and they act together on nuclear receptors LXRs, PPARs, PXR to exert their pharmacodynamic effects. Based on plant lipidomics technology, the present project analyzes the multi-dimensional lipid profiles Using GC-MS/MS or UPLC-MS/MS methods, for distinguishing species in Sargassum genus and obtaining Chemotaxonomy markers. Target to metabolic nuclear receptors, virtual drug screening of SARGASSUM lipids are carried out, and a seaweed-lipid database containing chemical and biology information was established. Through the established "chemical network-biological network", pharmacodynamics markers are obtained. Q-markers are then extracted from the integrated Chemotaxonomy markers and pharmacodynamic markers. Then, a simple, reliable and economical method for chemical identification of SARGASSUM is development. This study guarantees the safety and effectiveness of SARGASSUM clinical use, and promotes the construction of “China Blue Pharmacy Plan”.