成年中枢神经再生异常与多种神经系统疾病的发生密切相关，通过一些调控因子实现中枢神经系统的自我修复或再生，将为相关神经系统疾病提供新的治疗方案。本课题组在前期研究中，从2种大戟科白饭树属植物中分离鉴定出一系列结构新颖的生物碱类成分，其中部分化合物显示出良好的促神经元分化和突触形成的活性。初步的作用机制研究结果显示，这些生物碱类成分可提高Akt、ERK等蛋白的磷酸化水平，且可能与其调控神经元分化的活性有关。本项目拟在前期工作基础上，对聚花白饭树等4种白饭树属植物中的生物碱类成分进行深入的化学成分研究，发现一些结构新颖的生物碱类成分，并对其促神经分化作用进行评价及开展构效关系和作用机制研究，以期发现一些活性显著、毒副作用小、作用机制明确的新药先导物，为治疗中枢神经系统疾病的新药研发提供科学依据。

Neurogenesis in the adult central nervous system is tightly controlled and its dysregulation is frequently related to neurological diseases. Stimulation of adult neurogenesis is believed as an effective strategy to replenish the neuronal pool for functional circuit wiring when existing neurons are dead due to injury or degeneration. Thus, targeting neurogenesis has become a new therapeutic intervening method for treating neurodegenerative diseases. Our previous phytochemical investigations on two species of genus Flueggea (Euphorbiaceae) had led to the isolation of a series of novel alkaloids, some of which exhibited beneficial effects for neuronal differentiation and synapse formation. Pilot studies on the molecular mechanism of selected active alkaloids showed that Akt and ERK dependent pathways are upregulated, which may attribute to the neuronal differentiation activities of these compounds. With the aim to find lead compounds for drug discovery, based on the previous study, we are planning to carry out systematic chemical studies on four species of plants of genus Flueggea to obtain much more novel alkaloids. Furthermore, the biological activities of those alkaloids on neurogenesis and differentiation, as well as their structure-activity relationship and action mechanism will also be investigated. Our findings could be used as scientific evidence for the new drug development for the treatment of neurological diseases such as neurodegenerative disease, brain injuries and mood disorders.