玉米根中靶向NMDA受体的神经保护与抗抑郁活性物质基础及作用机制的研究

抑郁症是一种高发病率、高复发率、高致残率的精神疾病。目前临床的抗抑郁药大多存在起效慢、耐药及严重副作用等问题。因此，寻找起效快、疗效高、不良反应少和耐受性好的新型抗抑郁药物，解决当前临床上重度抑郁症治疗药物匮乏的问题是当前抗抑郁新药研究的热点。玉米根是我国的主要农作物玉米的根，研究极少，尚未被开发利用，不仅造成资源浪费也不利于生态环境的治理。课题组前期对玉米根进行了初步的物质基础与功效研究，首次发现玉米根中对映-贝壳杉烷类通过作用于NMDA受体发挥神经保护和抗抑郁活性，但受限于分离的化合物数量有限，未获得明确的构效关系。本项目拟在前期研究的基础上，融合“化学导向”和“活性导向”的研究策略，从玉米根中快速发现、定向分离对映-贝壳杉烷类化合物，系统评价其神经保护与抗抑郁活性，明确其作用机制，获得确切的构效关系，为新型神经保护剂与抗抑郁药的研制奠定基础，也为玉米根的合理开发和利用提供科学依据。

Depression is a kind of mental illness with high morbidity，high recurrent rate and high disability rate. At present, most clinical antidepressants have problems of slow onset, drug resistance and severe side effects. Therefore, it is the current research focus to developed new antidepressants with rapid onset, high efficacy, less adverse reactions and good tolerance to alleviate a dire scarcity of drugs for major depression. Maize roots are the roots of the main food crop in China, not exploited owing to the rare related research including chemical constituents and pharmacological effects, and not only caused resource wastes but also not conducive to the governance of the ecological environment. Our group previously conducted a preliminary study on the material basis and efficacy of maize roots. We isolated and identified four new ent-kaurane diterpenoids and found the ent-kaurane diterpenoids part had neuroprotective in vitro and antidepressant activity in vivo. However, we failed to get the clear structure-activity relationship and perform further study in the mechanisms because of the limited compounds. Based on the previous research, we will rapidly isolate ent-kaurane diterpenoids from maize roots using the chemistry- and bioassay-guided strategies to obtain sufficient samples, evaluate their neuroprotection and anti-depression activity systematically. Finally, reveal the clear structure-activity relationship, define the mechanisms and drug target. Our studies would lay a foundation for the development of new neuroprotectants and antidepressants, also provides scientific basis for rational development and utilization of maize root.