Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

被引：18
|
作者：
Bai, Dafeng [1 ]
Jin, Ge [2 ]
Zhang, Dajun [2 ]
Zhao, Lini [2 ]
Wang, Mingyue [2 ]
Zhu, Qiwen [2 ]
Zhu, Lin [2 ]
Sun, Yan [2 ]
Liu, Xuan [2 ]
Chen, Xueying [2 ]
Zhang, Liqian [2 ]
Li, Wenbo [2 ]
Cui, Yan [2 ]
机构：
[1] Eleventh Peoples Hosp Shenyang, Dept Pharmacol, 103 Hai Tang St, Shenyang 110016, Liaoning, Peoples R China
[2] Shenyang Med Coll, Dept Pharmacol, Key Lab Behav & Cognit Neurosci Liaoning Prov, 146 Huanghe North St, Shenyang 110034, Liaoning, Peoples R China
来源：
JOURNAL OF PHYSIOLOGICAL SCIENCES | 2019年 / 69卷 / 04期
关键词：
Silibinin; Alzheimer's disease; A beta generation; A beta degradation; Antioxidant; TRANSGENIC MICE; MEMORY DEFICITS; MOUSE MODEL; NEURON LOSS; ALZHEIMERS; PEPTIDE; IMPAIRMENT; METABOLISM; BRAIN; BACE1;
D O I：
10.1007/s12576-019-00682-9
中图分类号：
Q4 [生理学];
学科分类号：
071003 ;
摘要：
Silibinin has been shown to attenuate cognitive dysfunction and inhibit amyloid-beta (A beta) 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 beta-secretase levels, A beta 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 A beta deposition and the levels of soluble A beta 1-40/1-42 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 A beta pathology.
引用
收藏
页码：643 / 652
页数：10
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