钩吻广泛分布于我国南方地区，其全株均有剧毒，误食少量即可致人死亡。近几十年来，钩吻中毒或致死的事件屡见不鲜，已至少造成数百人死亡。然而，钩吻中毒的毒性成分不明确，毒理机制不清楚，限制了其临床救治。本课题组在前期研究中，对从钩吻枝叶和根中获得的单萜吲哚生物碱进行了初步的毒性评价，发现部分humantenine型和gelsedine型生物碱具有强烈毒性，并首次发现毒性成分可通过血脑屏障和抑制延髓脑片的神经放电，从而抑制呼吸中枢而产生毒性。本项目拟在前期工作基础上，进一步对钩吻植物不同部位的生物碱类成分进行分离和鉴定，评价它们对延脑呼吸中枢的抑制作用，阐明结构-毒性关系和毒理机制，为钩吻中毒临床救治的方案制定提供科学依据。

Gelsemium elegans is mainly distributed in south China. Since the whole plant is toxic, eating very small amounts of the plant can cause death. In recent decades, the poisoning or death events caused by Gelsemium elegans are usually reported, which has caused at least hundreds of deaths. However, the related fundamental research of Gelsemium poisoning is still very weak. The toxic components and the toxicological mechanism are still unclear, resulting in ineffective clinical treatment. In the previous work, we found that both humantenine and gelsedine type alkaloids from Gelsemium elegans are responsible for its toxic. Preliminary mechanism studies have shown that the toxic components can pass through the blood-brain barrier and inhibit the neuronal discharge of brainstem slices. The above findings suggest that these alkaloids could act on the respiratory center to produce their toxicity. However, the toxicological mechanism and structure-toxicity relationship need to be further studied. This project is based on the previous work and to build a library of natural product analogues by further isolation of Gelsemium alkaloids. In addition, this project will study the toxicity, toxicological mechanism and structure-toxicity relationship of Gelsemium alkaloids, which will provide scientific information for the development of effective clinical treatment method.