Ameliorating effect of Zishui Qinggan Yin on lipopolysaccharide-induced depressed mice and its effect on ERK/NF-κB pathway
Objective The aim of this study was to investigate the antidepressant effect and potential mechanism of Zishui Qinggan Yin(ZSQGY)in the LPS-induced depression mice model.Methods A mouse depression model was established by LPS.A total of 60 mice were randomly selected and randomly divided into six groups according to the random number table,namely control group,model group,Flu group(10 mg·kg-1),ZSQGY low,medium and high dose(8.835,17.670,35.340 g·kg-1)groups.After 14 days of administration,the control group was injected with the same amount of normal saline.The other groups were ip injected with LPS(0.83 mg·kg-1).After 24 h LPS injection,mice are weighed and the tail suspension test and forced swimming test were performed.The morphological changes of mice hippocampus were observed by HE staining and Nishi staining,and immunofluorescence staining was used to detect the fluorescence intensity of hippocampal microglia marker Iba-1.The activity of superoxide dismutase(SOD),malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and 5-hydroxytryptamine(5-HT)in serum of mice and the levels of IDO 1,KYN,and 5-HT in the hippocampus of mice were detected by kits.The expression of p-NF-κB,p-ERK,and ERK protein level in mouse hippocampus was detected by Western blotting.Results Compared with model group,the body weight of mice in the ZSQGY group increased(P＜0.05).The immobility time in the tail suspension experiment and forced swimming experiment of mice in each treatment group was significantly shortened(P＜0.05,0.01).The morphology of the hippocampus improved in each treatment group,and the expression of the hippocampal microglial cell marker Iba-1 was significantly reduced(P＜0.05).The levels of 5-HT in the serum of mice in the middle and high-dose groups of ZSQGY and the Flu group were significantly increased(P＜0.05),the activity of SOD in serum was significantly enhanced in each treatment group(P＜0.05),and the levels of TNF-α,IL-6,IL-1β,and MDA in serum were significantly decreased(P＜0.05,0.01).The levels of IDO1 and KYN in hippocampus were significantly decreased in each treatment group(P＜0.05,0.01),the level of 5-HT in hippocampus was significantly increased in medium-dose and high-dose ZSQGY group and fluoxetine hydrochloride group(P＜0.05,0.01).The protein expressions of p-ERK and p-NF-κB in hippocampus were significantly decreased in each treatment group(P＜0.05,0.01).Conclusion ZSQGY can significantly improve the depression-like behavior in LPS-induced mice and the mechanism may be related to down-regulating ERK/NF-κB signaling pathway and IDO1 level.
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