Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus

被引:44
作者
Li, Xiao-Juan [1 ]
Ma, Qing-Yu [1 ]
Jiang, You-Ming [1 ]
Bai, Xiao-Hui [1 ]
Yan, Zhi-Yi [1 ]
Liu, Qun [1 ]
Pan, Qiu-Xia [1 ]
Liu, Yue-Yun [1 ]
Chen, Jia-Xu [1 ]
机构
[1] Beijing Univ Chinese Med, Sch Basic Med Sci, 11 North Third Ring Rd, Beijing 100029, Peoples R China
基金
中国国家自然科学基金;
关键词
TUMOR-NECROSIS-FACTOR; ANXIETY-LIKE BEHAVIOR; STEROID ALPHA-SPINASTEROL; OXIDO-NITROSATIVE STRESS; ELEVATED PLUS-MAZE; ANIMAL-MODELS; TNF-ALPHA; DEPRESSION; ACTIVATION; APOPTOSIS;
D O I
10.1038/s41598-017-00496-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor-alpha (TNF-alpha) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF-alpha/JAK2-STAT3 pathway in the hippocampus. We examined the effects of Xiaoyaosan on behaviours exhibited in the elevated plus maze test, open field test and novelty-suppressed feeding test as well as hippocampal neuron damage and changes in the TNF-alpha/ JAK2-STAT3 pathway in a rat model of chronic immobilization stress (CIS)-induced anxiety. Xiaoyaosan exerts anxiolytic-like effects on CIS-induced anxiety, with a significant alleviation of anxiety-like behaviours, an attenuation of hippocampal neuron damage, and a reversal of the activation of the TNF-alpha/JAK2-STAT3 pathway in the hippocampus that are similar to the effects of the JAK2 antagonist AG490. However, Xiaoyaosan and AG490 failed to effectively regulate apoptosis-related factors, including Bax and Caspase-3. These results suggest that Xiaoyaosan attenuates stress-induced anxiety behaviours by down-regulating the TNF-alpha/JAK2-STAT3 pathway in the rat hippocampus.
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页数:13
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