Effect of antioxidant flavanone, naringenin, from Citrus junos on neuroprotection

Effect of antioxidant flavanone, naringenin, from Citrus junos on neuroprotection
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DOI:
10.1021/jf035079g
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发表时间:
2004-03-24
影响因子:
6.1
通讯作者:
Shin, DH
Shin, DH
中科院分区:
农林科学1区
文献类型:
--
作者:
Heo, HJ;Kim, DO;Shin, DH

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淀粉样蛋白P蛋白(Abeta)诱导的自由基介导的神经毒性被认为是阿尔茨海默病病因的主要假设。Abeta增加PC 12神经细胞中自由基的产生和脂质过氧化,导致细胞凋亡和细胞死亡。采用PC 12细胞研究了从柑橘中分离的主要黄烷酮成分柚皮素对Abeta诱导的神经毒性的保护作用。用分离的柚皮素和维生素C预处理防止了Abeta诱导的活性氧的产生。柚皮素以浓度依赖性的方式导致Abeta毒性的降低,这通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定来评估。然而,用这些抗氧化剂治疗抑制了Abeta诱导的神经毒性作用。还使用具有由东莨菪碱(lmg/kg体重)诱导的遗忘症的ICR小鼠评价了柚皮素的体内抗遗忘活性。当以4.5 mg/kg体重给予ICR小鼠时,柚皮素显著改善东莨菪碱诱导的健忘症,如在被动回避试验中所测量的。因此,这些结果表明,小分子A β诱导的体外氧化细胞应激被柚皮素降低,并且柚皮素可能是针对神经退行性疾病如阿尔茨海默病的有用的化学预防剂。
Amyloid P 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.