Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.
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-α (TNF-α) 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-α/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-α/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-α/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-α/JAK2-STAT3 pathway in the rat hippocampus.
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
Xiao-Juan
XJ
Li
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
Qing-Yu
0000-0002-4208-5634
QY
Ma
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
You-Ming
YM
Jiang
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
Xiao-Hui
XH
Bai
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
Zhi-Yi
ZY
Yan
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
Qun
Q
Liu
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
Qiu-Xia
QX
Pan
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
Yue-Yun
YY
Liu
School of Basic Medical Science, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China. chenjiaxu@hotmail.com.
Jia-Xu
JX
Chen
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000378:metabolism* / Q000517:prevention & control; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D004365:Drugs, Chinese Herbal; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha; C532268:xiaoyaosan; C507927:Jak2 protein, rat; D053614:Janus Kinase 2