Macranthol promotes hippocampal neuronal proliferation in mice via BDNF-TrkB-PI3K/Akt signaling pathway

被引:41
|
作者
Luo, Liu [1 ]
Liu, Xiao-Long [1 ]
Li, Jing [1 ]
Mu, Rong-Hao [1 ]
Liu, Qing [1 ,2 ]
Yi, Li-Tao [1 ,2 ]
Geng, Di [1 ,2 ]
机构
[1] Huaqiao Univ, Dept Chem & Pharmaceut Engn, Xiamen 361021, Fujian Province, Peoples R China
[2] Huaqiao Univ, Inst Pharmaceut Engn, Xiamen 361021, Fujian Province, Peoples R China
基金
中国国家自然科学基金;
关键词
Macranthol; Antidepressant; Brain-derived neurotrophic factor; K252a; UNPREDICTABLE MILD STRESS; MAJOR DEPRESSION; GENE-EXPRESSION; RATS; PATHOPHYSIOLOGY; NEUROGENESIS; NEUROBIOLOGY; PERICARPS; DISORDER; BURDEN;
D O I
10.1016/j.ejphar.2015.05.036
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Macranthol is a lignans natural product isolated from Illicium dunnianum Tutch. Our previous study has demonstrated that macranthol exerted an antidepressant-like effect in mice, at least in part, by increasing expression of hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the relationship between rnacranthol and BDNF downstream signaling pathway in the hippocampus remains unknown. The aim of this present study was to explore the mechanism of macranthol-modulated BDNF signaling pathway in a depression-like model of chronic unpredictable mild stress. Our results found that pharmacological inhibition of tropomyosin related kinase B (TrkB) with K252a abolished the improvement of macranthol on sucrose preference and immobility time, and attenuated the stimulatory effect of macranthol on hippocampal BDNF and phospho-Akt. Furthermore, K252a also reversed the improvement of macranthol on hippocampal Bcl-2, caspase-3 expression and hippocampal neuronal cell proliferation. Therefore, our findings verify that macranthol-mediated antidepressant-like action is associated with BDNF-TrkB and downstream activation of PI3K/Akt-Bcl-2/caspase-3 signaling pathway. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:357 / 363
页数:7
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