同源异效中药川楝子和川楝皮止痛和疗癣功效的物质基础及柠檬苦素抗炎镇痛机制研究

In Pharmacopoeia of China, the fruits of Melia toosendan (Meliaceae) are recorded as insecticidal and analgesic TCMs named “Chuan-Lian-Zi”, and its barks are one of the origins of anthelmintic and heal tinea medicines named “Ku-Lian-Pi”. Chemical researches have shown that toosendanin was the main active ingredients of their insecticidal effect, but the constituents representative their analgesic and heal tinea treatment efficacy have not been clarified comprehensively. Thus, based on the systematic study of limonoids constituents from a variety of folk medicinal plants from Meliaceae family, our project intends to systematically study the analgesic and antimicrobial active ingredients of homologous TCMs Chuan-Lian-Zi and Chuan-Lian-Pi with different effect guided by the analgesic and antifungal activity model, and discover novel limonoids with significant analgesic and antifungal activity in Chuan-Lian-Zi and Chuan-Lian-Pi respectively. Furthermore, the research of limonoids with significant analgesic activity based on anti-inflammatory and ion channel inhibition also should be carried out to clarify their target and action mechanism. This project is based on TCMs, and committed to clarify the active constituents represented its traditional efficiency, especially for those TCMs with same origin but different effects, which has important academic value. Its ideas and result also have important reference and exemplary affects for the research of other homologous but heterergic TCMs.

川楝是楝科楝属植物，其果实和茎(根)皮分别作为止痛杀虫中药川楝子和杀虫疗癣中药苦楝皮的来源之一被中国药典收载。化学成分研究表明，川楝素是其杀虫的主要活性成分，但与二者分别具有行气止痛和疗癣不同功效相关的物质基础并未见全面深入的研究。因此本项目拟在前期对多种楝科民间药用植物中柠檬苦素成分深入系统研究的基础上，以镇痛和抗真菌模型为指导，对同源异效中药川楝子和川楝皮的镇痛和抗真菌活性成分进行深入和系统的研究，阐明其止痛和疗廯功效的活性物质基础，以期发现分别具有抗炎镇痛和抗真菌的活性化合物。进一步深入研究具有显著镇痛活性的结构新颖的柠檬苦素基于抗炎和离子通道抑制的作用靶点，阐明其作用机制。本项目立足于传统中药，致力于中药传统功效物质基础的阐明，特别是针对来源相同而具有不同功效的中药深入研究其发挥不同功效的物质基础，具有重要的学术价值，研究思路和研究结果将对其他同源异效中药的研究起到借鉴和示范作用。

川楝是楝科楝属植物，其果实和茎(根)皮分别作为中药川楝子和中药苦楝皮的来源之一被中国药典收载。在4年的研究周期内，本项目首先对川楝皮、川楝子以及苦楝子中的柠檬苦素和三萜类成分开展了系统的定向寻找、快速分离、结构鉴定、生物活性筛选和作用机制研究。到目前已分离鉴定三萜和柠檬苦素成分52个，其中新化合物18个,部分化合物显示了显著的抗炎，细胞毒和逆转肿瘤细胞多药耐药活性。还从麻楝、香椿和滇红椿等楝科民间药物中发现了78个结构新颖复杂的具有抗炎和逆转肿瘤细胞多药耐药的柠檬苦素成分，其中新化合物28个。到目前，本项目的研究成果共发表以申请人为通讯作者（共同）和主要作者的并标注的SCI论文9篇，主要包括中药、植物药和天然药物研究领域著名杂志Fitoterapia，Phytochemistry Letters,Journal of Chromatography A等，另外还有5篇论文正在投稿或准备中。到目前，本项目已培养硕士研究生5名，还有1位博士研究生和2位硕士研究生将于2020年毕业。在本项目研究成果的支撑下，项目负责人获得2018年江苏省分析测试科学技术奖三等奖。本项目的研究成果不仅进一步阐明了川楝皮和川楝子的主要活性成分，也为创新药物的研究与开发提供了优良的柠檬苦素先导化合物。