延龄草属植物止血药效物质基础及其作用机制研究

Traditional Chinese medicine (TCM) is the precious wealth of Chinese ethnic people. However, the increasing consumption and the environmental degradation have led to many traditional Chinese medicine resources on the verge of depletion. To find the alternative medicinal plant resources is one of the important means to solve the shortage of traditional Chinese medicine resources. Chonglou (Paridis Rhizoma) is a valuable traditional Chinese medicine and has mainly been used in many Chinese patent medicines as hemostasis, anti-inflammatory and antiviral agents. Its resources is facing serious shortage because of the growing demand in recent years. In order to solve the shortage of Chonglou’s resources, our group recently found that the crude extract of Trillium tschonoskii exhibited stronger significant hemostatic activity than that of the extract of Chonglou based on the plant genetic relationship and the history of medicinal plants. A series of steroidal saponins had been isolated from this plant. Among them, two pennogenin saponins Tb and Tc showed better hemostatic effect than that of Paris saponin Tg in Chonglou. The content of saponins Tb, Tc, and Tg in T. tschonoskii is more than 2%. Based on the previous study, the chemical constituents of bioactive fractions of Trillium species will be investigated systematically. Then, the evaluation of their hemostatic activity, structure-relationship and functional mechanism of hemostatic activity will be carried out. Furthermore, we will clarify whether the Trillium species may replace Chonglou in the hemostatic components by LC-MS analysis. This research has important academic significance and application value to alleviate the shortage of Chonglou’s resources and the research and development of new hemostatic drugs.

中药是中华民族的宝贵财富，然而，日益剧增的消耗量和环境恶化使很多中药资源濒临枯竭，可替代药用植物资源的寻找是解决中药资源短缺或濒危的重要手段之一。重楼是我国名贵中药，主要用于止血、消炎、抗病毒等中成药中，近年来激增的需求量已使该资源面临严重短缺。为了解决该药材资源的短缺，申请人近期根据植物亲缘关系和民间药用背景，发现吉林延龄草提取物具有强于重楼提取物的止血效果，并从中分离得到系列甾体皂苷，发现2个偏诺皂苷Tb和Tc表现出比重楼中止血活性最强的重楼皂苷Tg更强的止血活性，且含量可达2%以上，极具开发潜力。本项目拟在前期工作基础上，对延龄草属植物止血活性部位进行系统的药效物质基础研究，开展单体化合物的止血活性、构效关系和作用机制研究；同时，借助LC-MS等手段，从活性成分角度评价延龄草属能否可以替代重楼，对缓解重楼资源的短缺及止血新药的研发均具有重要的学术意义和应用价值。

为了寻找重楼替代性或富含止血性偏诺皂苷植物资源，该项目系统研究了延龄草属植物吉林延龄草和延龄草中止血物质基础。从以上两种植物中共分离鉴定化合物90个，包括30个新甾体皂苷和一个新的倍半萜苷。生物活性结果研究表明，该两种植物的提取物及其甾体皂苷精制部位均具有优于“宫血宁”胶囊原料药的止血活性；该两种植物均富含三种偏诺皂苷，即Tg、Tb和Tc，而且后两者的止血活性均强于重楼中的主要止血成分–重楼皂苷VII；此外，部分化合物还表现出了很好的抗真菌、抗肿瘤和抗炎活性。该项目的完成，不仅阐明了延龄草属植物中主要止血成分和极大地丰富了天然甾体皂苷类成分的多样性，而且为该属植物的进一步开发与利用提供坚实物质基础和科学依据。