Zhe Qian, Sulei Wang, Weiwei Tao, Hongyan Long, Jianwei Wang
Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Metab Brain Dis. 2017 Apr;32(2):415-426. doi: 10.1007/s11011-016-9925-8. Epub 2016 Oct 30.
Jiao-Tai-Wan (JTW), has been usually used for insomnia in traditional Chinese medicine (TCM). The previous study shown that JTW was benefit for depression-like behavior, but the possible mechanism is not clear. This study is to determine whether JTW was benefit for the treatment of lipopolysaccharide (LPS)-induced depression-like behavior in mice and explore its possible mechanism. All drugs were intragastrically administered once daily for 7 consecutive days. On the 7th day, LPS was injected into mice 30 min after drug administration. Behavioral tests were performed 24 h after LPS administration. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). The 5-hydroxytryptamine (5-HT) and nor-epinephrine (NE) levels in prefrontal cortex were determined by UPLC-MS. The protein expressions of NF-κB signaling in prefrontal cortex were determined by western blot. Behavioral tests were measured via tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT) and open field test (OFT). In addition, effects of JTW on the TNF-α induced depressive-like behavior were also examined. Pretreatment with JTW (4.2 and 8.4 g/kg) or fluoxetine (20 mg/kg) effectively attenuated LPS-induced upregulations of the serum TNF-α and IL-6 contents and JTW (4.2 and 8.4 g/kg) or fluoxetine (20 mg/kg) effectively increased the contents of 5-HT and NE compared with LPS-treated group. Meanwhile, the western blot analysis results indicated the correlation between the antidepressant activity of JTW and the regulation of NF-κB signaling in brain. Besides, JTW (4.2 and 8.4 g/kg) or fluoxetine (20 mg/kg) significantly shortened LPS-induced increases in immobility time of TST, FST and weakened the reduction of the sucrose preference in SPT without significant alterations of locomotor activity in OFT. Additionally, JTW effectively reversed the depressive-like behavior induced by TNF-α (0.1 fg/site, i.c.v.). Our findings indicated that Jiao-Tai-Wan (JTW) played an important role in monoaminergic response and anti-inflammation in lipopolysaccharide (LPS)-induced mouse model, which may be therapeutically exploited to alleviate depression-like behavior.
交泰丸(JTW)常用于中医治疗失眠。先前的研究表明,交泰丸对抑郁样行为有益,但可能的机制尚不清楚。本研究旨在确定交泰丸是否对治疗小鼠脂多糖(LPS)诱导的抑郁样行为有益,并探讨其可能的机制。所有药物均连续7天每天灌胃给药一次。在第7天,给药30分钟后给小鼠注射LPS。在注射LPS 24小时后进行行为测试。采用酶联免疫吸附测定(ELISA)法检测血清白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α水平。采用超高效液相色谱-质谱联用(UPLC-MS)法测定前额叶皮质中5-羟色胺(5-HT)和去甲肾上腺素(NE)水平。采用蛋白质免疫印迹法检测前额叶皮质中NF-κB信号通路的蛋白表达。通过悬尾试验(TST)、强迫游泳试验(FST)、蔗糖偏好试验(SPT)和旷场试验(OFT)进行行为测试。此外,还研究了交泰丸对TNF-α诱导的抑郁样行为的影响。交泰丸(4.2和8.4 g/kg)或氟西汀(20 mg/kg)预处理可有效减轻LPS诱导的血清TNF-α和IL-6含量上调,与LPS处理组相比,交泰丸(4.2和8.4 g/kg)或氟西汀(20 mg/kg)可有效增加5-HT和NE的含量。同时,蛋白质免疫印迹分析结果表明交泰丸的抗抑郁活性与大脑中NF-κB信号通路的调节之间存在相关性。此外,交泰丸(4.2和8.4 g/kg)或氟西汀(20 mg/kg)显著缩短了LPS诱导的TST、FST不动时间增加,并减弱了SPT中蔗糖偏好的降低,而OFT中的运动活性没有显著改变。此外,交泰丸有效逆转了TNF-α(0.1 fg/部位,脑室内注射)诱导的抑郁样行为。我们的研究结果表明,交泰丸(JTW)在脂多糖(LPS)诱导的小鼠模型的单胺能反应和抗炎中起重要作用,这可能在治疗上被用于减轻抑郁样行为。