Biomol Ther  
Neuroprotective Effects of Spinosin on Recovery of Learning and Memory in a Mouse Model of Alzheimer’s Disease
Fanxing Xu1,2, Bosai He3, Feng Xiao3, Tingxu Yan4, Kaishun Bi5, Ying Jia3,* and Zhenzhong Wang1,*
1Jiangsu Kangyuan Pharmaceutical Co., Ltd., Lianyungang 222047,
2Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016,
3Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016,
4School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016,
5School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
E-mail: jiayingsyphu@126.com (Jia Y), wzhzh-nj@163.com (Wang Z)
Tel: +86-24-2398-6933 (Jia Y), +86-518-8115-2367 (Wang Z)
Fax: +86-24-2398-6259 (Jia Y), +86-518-8115-2367 (Wang Z)
Received: March 19, 2018; Revised: May 2, 2018; Accepted: May 8, 2018; Published online: June 21, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer’s disease (AD) induced by Aβ1-42 and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin (100 μg/kg/day), the cognitive impairment of mice induced by Aβ1-42 was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and Aβ1-42 accumulation in hippocampus. Aβ1-42 induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression,suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.
Keywords: Spinosin, Semen Ziziphi spinosae, Alzheimer’s disease, Neuroprotection


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