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


Department of Pharmacology, Key Laboratory of Behavioral and Cognitive Neuroscience of Liaoning Province, Shenyang Medical Colleges, 146 Huanghe North Street, Yuhong District, Shenyang, Liaoning, 110034, People's Republic of China. [Email]


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.


Alzheimer’s disease,Antioxidant,Aβ degradation,Aβ generation,Silibinin,