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Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice.
The Journal of Physiological Sciences ( IF 2.6 ) Pub Date : 2019-05-13 , DOI: 10.1007/s12576-019-00682-9
Dafeng Bai 1 , Ge Jin 2 , Dajun Zhang 2 , Lini Zhao 2 , Mingyue Wang 2 , Qiwen Zhu 2 , Lin Zhu 2 , Yan Sun 2 , Xuan Liu 2 , Xueying Chen 2 , Liqian Zhang 2 , Wenbo Li 2 , Yan Cui 2
Affiliation  

Silibinin has been shown to attenuate cognitive dysfunction and inhibit amyloid-beta (Aβ) aggregation in Alzheimer's disease (AD) models. However, the underlying mechanism by which silibinin improves cognition remains poorly understood. In this study, we investigated the effect of silibinin on β-secretase levels, Aβ enzymatic degradation, and oxidative stress in the brains of APP/PS1 mice with cognitive impairments. Oral administration of silibinin for 2 months significantly attenuated the cognitive deficits of APP/PS1 mice in the Y-maze test, novel object recognition test, and Morris water maze test. Biochemical analyses revealed that silibinin decreased Aβ deposition and the levels of soluble Aβ1-40/1-42 in the hippocampus by downregulating APP and BACE1 and upregulating NEP in APP/PS1 mice. In addition, silibinin decreased the MDA content and increased the activities of the antioxidant enzymes CAT, SOD, and NO. Based on our findings, silibinin is a potentially promising agent for preventing AD-associated Aβ pathology.

中文翻译:


天然水飞蓟宾调节 APP/PS1 小鼠中淀粉样蛋白前体蛋白的加工和淀粉样蛋白-β 蛋白的清除。



水飞蓟宾已被证明可以减轻阿尔茨海默病 (AD) 模型中的认知功能障碍并抑制淀粉样蛋白 -β (Aβ) 聚集。然而,水飞蓟宾改善认知的潜在机制仍然知之甚少。在这项研究中,我们研究了水飞蓟宾对认知障碍 APP/PS1 小鼠大脑中 β 分泌酶水平、Aβ 酶促降解和氧化应激的影响。口服水飞蓟宾2个月可显着减轻APP/PS1小鼠在Y迷宫测试、新物体识别测试和Morris水迷宫测试中的认知缺陷。生化分析表明,水飞蓟宾通过下调 APP/PS1 小鼠的 APP 和 BACE1 并上调 NEP,减少海马中的 Aβ 沉积和可溶性 Aβ1-40/1-42 的水平。此外,水飞蓟宾还能降低MDA含量并提高抗氧化酶CAT、SOD和NO的活性。根据我们的研究结果,水飞蓟宾是一种有前景的预防 AD 相关 Aβ 病理的药物。
更新日期:2019-11-01
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