Effects of Jiaotaiwan on depressive-like behavior in mice after lipopolysaccharide administration

Abstract

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.

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