神经退行性疾病(如PD、AD等)是影响人类健康的重大疾病，其发病机制尚不完全明确，无特效治疗药物。神经生长因子(NGF)能促进中枢和外周神经生长、分化，目前已用于AD等神经系统疾病的临床试验，但由于其蛋白质的理化性质限制了其成为治疗用药。因此，从天然产物中寻找促神经细胞分化的小分子化合物具有重要意义。我们在前期工作中，从白饭树枝叶的总生物碱部位分离鉴定了一系列新型一叶萩型生物碱，部分化合物具有明显的促PC12和N2a细胞分化的作用，初步作用机制研究还表明，该类成分促PC12和N2a细胞分化活性均与激活ERK1/2信号通路有关。本项目拟在前期工作基础上，进一步对白饭树枝叶及其它部位中的一叶萩型生物碱进行系统的分离鉴定，评价该类成分促神经细胞分化的活性及构效关系，并深入阐明其对ERK1/2信号通路的调控机制，为治疗神经退行性疾病的小分子药物的研究与开发提供科学依据。

Neurodegenerative diseases (such as PD, AD, etc.) are the major diseases affecting human health as their etiology and pathogenesis are not clear and there are no specific drugs. NGF can promote the central and peripheral nerve growth, differentiation and survival, which has been developed for peripheral sensory neuropathy and AD. However, some protein natures of NGF limit it to be an ideal clinical medicine. As a result, it is important to discover small molecule drugs with nerve cell differentiation activity for the treatment of neurodegenerative diseases. Our previous phytochemical study on the twigs and leaves of Flueggea virosa had led to the isolation of numbers of new Securinega alkaloids, some of which had induced the neuronal differentiation of PC12 and N2a cells and activated ERK1/2. On the basis of preliminary work, the project aims to the thorough chemical research of Securinega alkaloids from the twigs and leaves, roots and fruits of this plant and will further evaluate the activities of these compounds regulating nerve cell differentiation via the activation of ERK1/2 as well as the mechanism and structure-activity relationship. It is supposed to be a scientific basis for the development of neurodegenerative diseases.