检测10种新型香豆素衍生物的神经保护作用,并对其可能的机制进行初步探索。采用MTT法筛选10个香豆素衍生物对神经毒性剂(Aβ25-35及鱼藤酮)或氧糖剥夺(OGD)所致神经细胞损伤的保护作用,获得活性较好的化合物;采用显微形态学观察各种神经毒性剂模型下该化合物的作用情况;通过脂多糖(LPS)致小胶质细胞炎症病变,并采用ELISA法检测化合物对炎症因子的抑制作用;最后,检测此化合物对自由基的直接清除能力。化合物3不但对3种神经元毒性模型所致细胞存活率降低均有显著的改善作用,而且能显著抑制神经胶质细胞炎症模型中炎症因子(TNF-α,IL-1β)的释放。另外,化合物3具有很好的自由基清除能力,对超氧阴离子的清除能力相当于维生素C。化合物3显著的超氧阴离子的清除作用可能是其重要的神经保护机制。化合物3作为一种潜在的神经保护剂,值得进一步研究。
The study reports the detection of neuroprotective effect of 10 kinds of coumarin derivatives and explores their possible mechanism. MTT method was used to screen the neuroprotective effect of 10 coumarin derivatives on neurotoxic agents (Afl25-35 and rotenone) or OGD (oxygen-glucose deprivation). A compound with better protective effect was obtained. Then the effect of this compound on neurotoxic agents on PC12 was detected by the morphological observation. Furthermore, the effect of compound 3 on microglia with lipopolysaccharide (LPS) induced inflammation was detected. And the inflammatory factor was tested. Finally, direct free radical scavenging ability was detected. Compound 3 was found to be the best compound through three neurons toxic models. Not only compound 3 ameliorated cell viability reduced by three neurons toxic models, but also significantly inhibited the production of inflammatory factor (TNF-a and IL-1β). And its free radical scavenging ability is very good, especially the effect on superoxide anion, which is comparable with vitamin C. The significant scavenging effect of compound 3 on superoxide anion might be the mechanism of the neuroprotection. Compound 3 as a potential neural cell protective agent merits further investigation.