Heo Ho Jin, Kim Dae-Ok, Shin Soo Cheol, Kim Mi Jeong, Kim Byung Gee, Shin Dong-Hoon
Department of Food Science and Technology, Cornell University, Geneva, New York 14456, USA.
J Agric Food Chem. 2004 Mar 24;52(6):1520-5. doi: 10.1021/jf035079g.
Amyloid beta protein (Abeta)-induced free radical-mediated neurotoxicity is known as a leading hypothesis for a cause of Alzheimer's disease. Abeta increased free radical production and lipid peroxidation in PC12 nerve cells, resulting in apoptosis and cell death. The protective effect of naringenin, a major flavanone constituent isolated from Citrus junos, against Abeta-induced neurotoxicity was investigated using PC12 cells. Pretreatment with isolated naringenin and vitamin C prevented the generation of the Abeta-induced reactive oxygen species. Naringenin resulted in the decrease of Abeta toxicity in a manner of concentration dependence, which was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. However, treatment with these antioxidants inhibited the Abeta-induced neurotoxic effect. The antiamnestic activity of naringenin in vivo was also evaluated using ICR mice with amnesia induced by scopolamine (1 mg/kg body weight). Naringenin, when administered to ICR mice at 4.5 mg/kg body weight, significantly ameliorated scopolamine-induced amnesia as measured in the passive avoidance test. Therefore, these results indicate that micromolecular Abeta-induced in vitro oxidative cell stress is reduced by naringenin and naringenin may be a useful chemopreventive agent against a neurodegenerative disease such as Alzheimer's disease.
β淀粉样蛋白（Aβ）诱导的自由基介导的神经毒性是阿尔茨海默病病因的主要假说之一。Aβ增加了PC12神经细胞中的自由基产生和脂质过氧化，导致细胞凋亡和死亡。使用PC12细胞研究了从温州蜜柑中分离出的主要黄酮成分柚皮素对Aβ诱导的神经毒性的保护作用。用分离出的柚皮素和维生素C预处理可防止Aβ诱导的活性氧生成。柚皮素以浓度依赖性方式降低了Aβ毒性，这通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐测定法进行评估。然而，用这些抗氧化剂处理可抑制Aβ诱导的神经毒性作用。还使用东莨菪碱（1mg/kg体重）诱导失忆的ICR小鼠评估了柚皮素在体内的抗遗忘活性。当以4.5mg/kg体重给ICR小鼠施用柚皮素时，在被动回避试验中测得其显著改善了东莨菪碱诱导的失忆。因此，这些结果表明柚皮素可减轻体外Aβ诱导的氧化细胞应激，并且柚皮素可能是预防神经退行性疾病如阿尔茨海默病的有用化学预防剂。
