艾叶和野艾蒿叶中倍半萜类成分及其镇痛活性研究

In our preliminary study, sesquiterpenoid fraction from the leaves of Artemisia argyi has the significant analgesic activity on mice. Moreover, the sesquiterpenoid fraction and some sesquiterpenoid compounds isolated from A. argyi exhibited potential inhibitory activity toward COX-2. According to the utility theory of analgesic effect of A. argyi and our previous research, it is indicated sesquiterpenoids possibly is one of the analgesic constituents of Artemisiae argyi folium, and the analgesic mechanism is possibly realized through inhibiting arachidonic acid metabolism. In addition, the leaves of A. lavandulaefolia is one of the most widespread substitution of the leaves of A. argyi. It is worthy of further study whether A. lavandulaefolia is rich in analgesic sesquiterpenoid. Therefore, the main research contents of this project include three parts. Firstly, study on the sesquiterpenoids from the leaves of A. argyi and A. lavandulaefolia. Secondly, study on the analgesic activities of the sesquiterpenoids obtained from the two different species. Thirdly, study on the differences between sesquiterpenoid constituents and their analgesic activities of the leaves of A. argyi and A. lavandulaefolia. These researches will provide some basis for clarifying substantial base of analgesic effects of Artemisiae argyi folium, evaluating the scientificity about the leaves of A. lavandulaefolia, which is used as a substitution of Artemisiae argyi folium, and looking for and discovering novel analgesic lead compounds.

本项目基于对中药艾叶止痛传统功效的深刻理解，同时结合本课题组前期的化学和药理研究工作基础，发现艾叶中倍半萜组分群具有显著的镇痛活性，且该组分群和从中分离得到的部分倍半萜单体化合物对COX-2显示出明显的抑制作用。故我们推测：艾叶中倍半萜类成分可能是其发挥镇痛作用的有效成分之一，其镇痛的作用机制可能是通过阻断花生四烯酸代谢途径而实现。野艾蒿叶是艾叶最常见的代用品之一，野艾蒿叶中是否含有倍半萜类化合物，该类成分是否亦具有镇痛活性值得深入研究，且未见有文献报道。因此本项目拟开展：1. 艾叶和野艾蒿叶中倍半萜类化学成分研究；2. 艾叶和野艾蒿叶中倍半萜类化合物镇痛活性研究；3. 艾叶和野艾蒿叶中倍半萜类成分及其镇痛活性的差异性研究。本研究可为阐明“艾叶”镇痛的效应物质基础提供依据，为评价野艾蒿叶作为“艾叶”资源的科学性提供理论基础，同时可为发现新型的具有镇痛作用的药物先导化合物奠定基础。

艾叶是我国临床常用中药之一，本课题组前期的化学和药理研究工作发现艾叶中倍半萜组分群具有显著的镇痛活性，且该组分群和从中分离得到的部分倍半萜单体化合物对COX-2显示出明显的抑制作用，故推测艾叶中倍半萜类成分可能是其发挥镇痛作用的有效成分之一。野艾蒿叶是艾叶最常见的代用品之一，野艾蒿叶中是否含有倍半萜类化合物，该类成分是否亦具有镇痛活性值得深入研究。. 本项目采用各种柱层析（Diaion HP-20、硅胶、Sephadex LH-20、ODS等）及半制备HPLC等分离技术和NMR、MS、UV、IR、X-ray等结构鉴定技术，从艾叶中共分离鉴定了75个化合物，其中倍半萜类化合物37个，包括7个新的倍半萜，其中一个结构新颖的倍半萜聚合物；此外还分离得到2个新的黄酮类化合物。从野艾蒿叶中共分离鉴定了30个化合物，其中倍半萜类化合物17个，包括3个新的倍半萜，其中一个稀有的倍半萜内酯，具有一个愈创木烷重排骨架。采用小鼠醋酸扭体模型和二甲苯诱导小鼠耳肿胀模型开展了艾叶和野艾蒿叶不同部位抗炎镇痛活性研究，发现了其抗炎镇痛活性部位。同时开展了艾叶和野艾蒿叶不同部位及部分化合物的COX-2抑制活性研究，筛选出了艾叶和野艾蒿叶COX-2抑制活性部位，以及一些COX-2抑制活性倍半萜。. 本研究可为阐明艾叶镇痛的效应物质基础提供一定的依据，为促进艾叶和野艾蒿叶资源的开发利用奠定一定的基础。