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大脑中β-淀粉样蛋白(β-amyloid,Aβ)过量积累与神经细胞的凋亡和氧化应激密切相关,是导致阿尔茨海默病(AD)发病的有害因素。因此,寻找能够对抗Aβ诱导的神经毒性的小分子活性化合物作为先导化合物或候选化合物,是治疗或延缓AD病情发展的重要策略。我们使用MTT法在SH-SY5Y细胞上检测到CF-1((1R,2S,4R,5S,7R,9S,10S)-1,15-diacetoxy-2-benzoyloxy-9-cinnamoyloxy-β-di-hydroagarofuran)能够浓度依赖地缓解Aβ_(25-35)造成的神经毒性;DAPI染色提示CF-1的神经保护作用与其抗细胞凋亡作用有关;Western blot方法检测到CF-1可以显著抑制Aβ_(25-35)诱导的cleaved Caspase-3的表达,佐证了其抗凋亡的作用;CF-1预处理能够显著降低Aβ_(25-35)引起的胞内ROS积累,但对DPPH无清除作用。总之,我们的研究首次证明,化合物CF-1可通过阻止Aβ诱导的细胞凋亡和氧化应激作用来发挥神经保护作用。因此,CF-1作为AD治疗的先导化合物或候选化合物具有潜在价值。
The excessive accumulation of β-amyloid (Aβ) in the brain is closely related to apoptosis and oxidative stress in nerve cells and is a harmful factor in the pathogenesis of Alzheimer’s disease (AD). Therefore, looking for small molecule active compounds capable of antagonizing Aβ-induced neurotoxicity as a lead compound or candidate compound is an important strategy for treating or delaying the progression of AD. We detected CF-1 ((1R, 2S, 4R, 5S, 7R, 9S, 10S) -1,15- diacetoxy- 2 -benzoyloxy-9-cinnamoyloxy-β-di- hydroagarofuran could relieve the neurotoxicity induced by Aβ_ (25-35) in a concentration-dependent manner. DAPI staining suggested that the neuroprotective effect of CF-1 was related to the anti-apoptotic effects of CF-1. The results of Western blot showed that CF-1 significantly inhibited Aβ_ (25 -35), and the anti-apoptotic effect of cleaved Caspase-3 was demonstrated. CF-1 pretreatment significantly decreased intracellular ROS accumulation induced by Aβ_ (25-35) but no effect on DPPH. In conclusion, our study, for the first time, demonstrates that compound CF-1 exerts neuroprotective effects by preventing Aβ-induced apoptosis and oxidative stress. Therefore, CF-1 has potential value as a lead compound or candidate compound for AD therapy.