线粒体是细胞能量生成的关键细胞器，其功能障碍在肿瘤发生、发展过程中起重要作用。线粒体存在众多药物靶点，如渗透转换孔复合体、电子传递链复合物及多种能量代谢酶等。很多中药可通过调节线粒体功能发挥抗肿瘤作用。但中药能否通过直接作用于线粒体发挥药效，哪些活性成分可作用于线粒体及作用机理尚不明确，此外线粒体为靶标的快速筛选方法的缺乏，严重限制中药线粒体靶向活性成分的发现及相关机制研究。本项目拟采用线粒体靶向筛选及LC/MS技术，建立筛选周期短、样品用量少、分析成本低，集“识别-鉴定-评价-寻靶”于一体的中药抗肿瘤活性成分群快速筛选体系，筛选土茯苓、桂枝茯苓丸等中药或复方中抗肿瘤活性成分群，并结合分子探针、结合竞争等技术、体内外研究探索其作用靶点及药效机制。本项目成果可提供一种活性物质筛选的通用性思路及方法，为中药药效物质基础及作用机制研究提供理论、技术支持，为先导化合物发现及抗肿瘤新药研发提供依据。

Mitochondria is the vital organelle of energy genesis in cells, which plays a key role in several important physiological and biochemical processes. Mitochondria dysfunction might lead to pathogenesis of many diseases, as a result of which, prevention and alleviation of mitochondria dysfunction has become an effective treatment. Nowadays, several drug targets have been found on mitochondria, such as mPTP, VDAC, PDK, LDH, IDH, and so on. Many traditional Chinese medicines (TCMs), such as ginseng, Sophorae Flavescentis Radix, Smilacis Glabrae Rhizoma, Scutellariae Barbatae Herba, could exhibit anti-tumor effect through regulation the function of mitochondria. However, whether TCMs could exhibit their therapeutical effects through those targets, which component in TCMs could directly act on those targets, or what is the mechanism, are still unknown. Besides, rapid and effective screening of active components in TCMs is still a bottleneck problem in the development of TCMs. Therefore, the present project will focus on the establishment of a rapid screening system, which combines recognition, identification, evaluation and target-searching, for discovery of novel anti-tumor components or components group in TCMs. And the new screening system will be used in the active components group searching in several TCMs or formulas, such as Smilacis Glabrae Rhizoma and Kushen injection, as well as their activity evaluations. Furthermore, this project will also apply molecular docking, molecular probe, and binding competition, for target searching, and and explain the mechanism of those active components. This project will provide a universal idea and method for high-performance active components searching, as well as the theoretical basis and experimental proof for pharmacology of TCMs.