线粒体损伤导致的功能障碍或紊乱引发诸如心脑血管疾病、神经退行性疾病、代谢性疾病、癌症和衰老等诸多重大健康问题。清除受损的线粒体对稳定细胞正常功能及防治各类疾病的发生发展有着极其重要的作用。最近，项目依托的课题组突破性发现了靶向核受体Nur77清除受损线粒体的新生物学机制。本项目将基于这一重大发现以及对苯酞类化合物的前期研究成果，进一步从当归、川芎、茶芎、藁本等伞形科含苯酞成分的中药中分离筛选调控Nur77清除受损线粒体的苯酞类化合物，再经过构效关系分析、计算机辅助设计、有机化学合成等方法完成有效成分的结构修饰与优化，并初步探讨筛选到的药物抗动脉粥样硬化的作用及与清除受损线粒体的关系。本课题将促进线粒体疾病机制及药物靶向治疗方面的研究，同时对从本质上认识当归、川芎等传统中药的功效有着重要的学术意义。项目预期获得有效清除受损线粒体的靶向药物或先导化合物2-3个，发表SCI学术论文2篇以上。

Damage and dysfunction of mitochondria may lead to significant health problems, such as cardiovascular diseases, neurodegenerative diseases, metabolic diseases, cancer and aging etc. The removal of unwanted or damaged mitochondria is essential for cellular homeostasis and key events in development of various diseases. Recently, our research group successfully found a novel biological mechanism targeting nuclear receptor Nur77 to clear damaged mitochondria. Based on the significant new discovery, together with the preliminary studies on phthalides, we will continue to screen the active phthalides from the traditional Chinese medicine such as Radix angelicae sinensis, Rhizoma chuanxiong, Ligusticum Chaxiong, and Rhizoma Ligustici, targeting Nur77 to eliminate damaged mitochondria. After validating biological activities, studying structure-activity relationship, exerting computer aided design, the structure of selected phthalides will be modified and optimized. The relationship between the activities of optimized structure on anti-atherosclerosis and elimination of damaged mitochondria will be further studied. This project will be beneficial to get a deeper insight into the mechanism of mitochondrial diseases and target drug treatment. It also has important academic significance to understand medicinal efficacy of traditional Chinese medicine like Radix angelicae sinensis and Rhizoma chuanxiong in essence. The project is expected to result 2-3 lead compounds or targeted drug candidates which can effectively eliminate the damaged mitochondria, and publish more than 2 SCI academic papers.