据统计，乙肝肝炎患者（包括病毒携带者）占我国总人口的十分之一。赶黄草为苗族传统药物，其全草具解毒、活血、平肝、健脾、祛黄疸等功效。目前对其主要成分的研究已有一定的报道，但未见代谢方面的研究。没食子酸和槲皮素是已报道的活性成分，但是在我们的前期研究中，发现二者含量很低，而另一种含量大的抗肝炎病毒成分（SCH 644343）被分离得到，另外，分离得到的短叶苏木酚据报道也有对急慢性肝损伤的保护作用。通过UPLC-QTOF 分析，我们还发现了很多具有类似结构的其他未知成分。因此，我们拟在此基础上，利用高通量的现代科技手段，对中药赶黄草的药效物质进行深入研究，寻找活性成分，探索中药成分群进入动物体内后的ADME 情况，为临床用药、新药研发提供依据；并据此建立科学合理的现代中药质量标，从整体（谱）和局部（量）两个方面评价中药质量。在研究过程中，将用到微透析、orbitrap MS、化学计量学等多种技术

Hepatitis, especially hepatitis B, seriously threaten the health of Chinese people. Some investigation reported that nearly ten percent of the Chinese people have suffered from hepatitis B.Penthorum chinense Pursh (Ganhuangcao in Chinese) is widely distributed in China, Japan, Korea and eastern Russia. It is used in Chinese medicine as a remedy for jaundice, edema and traumatic injury. Gansu, a prepared Chinese medicine from the extract of P. chinense, has been used in clinics for treating hepatitis and has proven to be effective for several yearsSome flavones and their glycosides, gallic acid were characterized from the plant. In previous study, we found that one abundant compound (SCH 644343) was reported to be an inhibitor of HCV NS3 protease. This is actually a new progress on investigation of Ganhuangcao. Furthermore, using UPLC-QTOF technique, more other structures, which was similar to that of SCH 644343, were found in extract of Ganhuangcao. This result suggested that further studies on the whole plants of P. Chinense should be carried out to determien the active components responsible for the pharmacological effects. ADME of the active components of Ganhuangcao will also be studied in rats. Based on results of the pharmacological and pharmacokinetics studies, quality standard of Ganhuangcao will be established. Fingerprint and simultanous determination of multiple markers will be used together to evaluate the medicine quality. A series of powerful techniques, such as UPLC-Orbitrap, microdialysis, chemometrics etc., will be used in this work.

本项目按照计划对民间保肝药物赶黄草进行了物质基础及质量控制研究。首先，用超高效液相色谱结合高分辨多级质谱对赶黄草主要成分进行了快速分析，从中初步鉴定了37个化合物，在此基础上，采用各种分离手段，分离纯化了其中的25个主要成分，并利用核磁共振谱对其结构进行了确证；其次，选取与肝代谢相关的核受体法尼酯衍生物X受体 (Famesoid X receptor, FXR)和孕烷X受体 (Pregnane X receptor, PXR)开展了关于保肝护肝的作用机制研究，遗憾的是所得到的主要化合物对所研究的受体均无明显激动作用，同时，对肝成纤维细胞的研究表明，所获得的主要化合物没有明显的细胞毒作用，因此，对赶黄草的保肝护肝作用机制还需更加全面的探索；再次，我们利用高效液相色谱法和超高效液相色谱法分别建立了赶黄草的指纹图谱，并且采用相似度软件和化学计量学方法分别对市售赶黄草样品进行了分析，结果表明，所建立的方法可以判别不同样品的优劣和真伪。同时，我们还对其中七个主要成分（据文献报道与保肝护肝作用有一定的相关性）进行了多指标成分同时定量分析，其中，超高效液相色谱的应用使分析效率大大提高。本项目的实施为赶黄草的临床用药、新药研发提供依据；为建立科学合理的现代中药质量标，从整体（谱）和局部（量）两个方面评价中药质量打下了基础。项目的执行过程中发表了标注受本项目资助的SCI文章4篇，联合培养硕士研究生一名，协助培养博士研究生二名，出站博士后一名。