Silibinin prevents amyloid β peptide-induced memory impairment and oxidative stress in mice
Silibinin prevents amyloid β peptide-induced memory impairment and oxidative stress in mice
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DOI：
10.1111/j.1476-5381.2009.00295.x
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发表时间：
2009-08-01
影响因子：
7.3
通讯作者：
Nabeshima, T.
中科院分区：
文献类型：
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作者：
Lu, P.;Mamiya, T.;Nabeshima, T.
背景和目的：积累的证据表明氧化应激与β淀粉样蛋白（Aβ）诱导的认知功能障碍有关。水飞蓟宾（水飞蓟宾）是一种从草本水飞蓟（Silybum marianum）中提取的黄酮类化合物，已被证明具有抗氧化特性；然而，目前尚不清楚水飞蓟宾是否能改善 Aβ 诱导的神经毒性。在本研究中，我们检测了水飞蓟宾对Aβ(25-35)引起的小鼠记忆障碍和氧化应激累积的影响。实验方法：将聚集的Aβ(25-35)(3nmol)脑室内给予小鼠。注射Aβ(25-35)后立即开始用水飞蓟宾(2、20和200mg中心点kg(-1)，每天一次，口服)治疗。在Aβ(25-35)治疗后6天评估运动活动，并在Aβ(25-35)治疗后6-11天在Y迷宫和新物体识别测试中评估认知功能。注射 A beta(25-35) 7 天后，测量海马中脂质过氧化（丙二醛）和抗氧化剂（谷胱甘肽）的水平。 主要结果：水飞蓟宾在 Y 迷宫和新物体识别测试中预防 A beta(25-35) 引起的记忆障碍。水飞蓟宾重复治疗可减轻Aβ(25-35)诱导的海马丙二醛积累和谷胱甘肽消耗。结论和意义：水飞蓟宾可预防Aβ(25-35)诱导的记忆障碍和氧化损伤，可能是阿尔茨海默病的潜在治疗剂。
Background and purpose:Accumulated evidence suggests that oxidative stress is involved in amyloid beta (A beta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silibinin improves A beta-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by A beta(25-35) in mice.Experimental approach:Aggregated A beta(25-35) (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg center dot kg(-1), once a day, p.o.) was started immediately after the injection of A beta(25-35). Locomotor activity was evaluated 6 days after the A beta(25-35) treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the A beta(25-35) treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the A beta(25-35) injection.Key results:Silibinin prevented the memory impairment induced by A beta(25-35) in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the A beta(25-35)-induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus.Conclusions and implications:Silibinin prevents memory impairment and oxidative damage induced by A beta(25-35) and may be a potential therapeutic agent for Alzheimer's disease.