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水飞蓟宾:一种新型的 Aβ 聚集抑制剂。

Silibinin: a novel inhibitor of Aβ aggregation.

机构信息

Research Center of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing, 400067, PR China.

出版信息

Neurochem Int. 2011 Feb;58(3):399-403. doi: 10.1016/j.neuint.2010.12.017. Epub 2010 Dec 24.

DOI:10.1016/j.neuint.2010.12.017
PMID:21185897
Abstract

Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid β peptide (Aβ) into extracellular fibrillar deposits known as amyloid plaque. Inhibition of Aβ aggregation is therefore viewed as a potential method to halt or slow the progression of AD. It is reported that silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), attenuates cognitive deficits induced by Aβ25-35 peptide and methamphetamine. However, it remains unclear whether silibinin interacts with Aβ peptide directly and decreases Aβ peptide-induced neurotoxicity. In the present study, we identified, through employing a ThT assay and electron microscopic imaging that silibinin also appears to act as a novel inhibitor of Aβ aggregation and this effect showed dose-dependency. We also show that silibinin prevented SH-SY5Y cells from injuries caused by Aβ(1-42)-induced oxidative stress by decreasing H(2)O(2) production in Aβ(1-42)-stressed neurons. Taken together, these results indicate that silibinin may be a novel therapeutic agent for the treatment of AD.

摘要

阿尔茨海默病(AD)的特征是淀粉样β肽(Aβ)异常聚集,形成称为淀粉样斑块的细胞外纤维状沉积物。因此,抑制 Aβ 聚集被认为是阻止或减缓 AD 进展的一种潜在方法。有报道称,水飞蓟素(奶蓟素),一种从奶蓟草(水飞蓟)中提取的类黄酮,可减轻 Aβ25-35 肽和安非他命引起的认知障碍。然而,目前尚不清楚水飞蓟素是否与 Aβ 肽直接相互作用并降低 Aβ 肽诱导的神经毒性。在本研究中,我们通过 ThT 测定和电子显微镜成像鉴定出,水飞蓟素似乎也可以作为 Aβ 聚集的新型抑制剂,且这种作用具有剂量依赖性。我们还表明,水飞蓟素通过减少 Aβ(1-42)应激神经元中 H2O2 的产生,防止 SH-SY5Y 细胞受到 Aβ(1-42)诱导的氧化应激引起的损伤。总之,这些结果表明水飞蓟素可能是治疗 AD 的一种新型治疗剂。

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Silibinin: a novel inhibitor of Aβ aggregation.水飞蓟宾:一种新型的 Aβ 聚集抑制剂。
Neurochem Int. 2011 Feb;58(3):399-403. doi: 10.1016/j.neuint.2010.12.017. Epub 2010 Dec 24.
2
Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice.水飞蓟宾减轻β-淀粉样蛋白(25-35)肽诱导的记忆损伤:诱导型一氧化氮合酶和肿瘤坏死因子-α在小鼠中的作用
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Silibinin prevents amyloid beta peptide-induced memory impairment and oxidative stress in mice.水飞蓟宾可预防淀粉样β肽诱导的小鼠记忆障碍和氧化应激。
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