The effect of Deoxyschizandrin on chronic unpredictable mild stress-induced depression.

The purpose of the present study was to evaluate the anti-depressant effect of Deoxyschizandrin (DEO) in chronic unpredictable mild stress (CUMS)-induced mice. The mice were subjected to CUMS paradigm for 8 weeks. From the sixth week, the mice were intragastrically treated with DEO once daily for continuous 3 weeks. The behavior tests including sucrose preference test (SPT), Forced swimming test (FST), Tail suspension test (TST), Open field test (OFT) were conducted. Additionally, the expressions of TLR4, MyD88, TRAF6, p-NF-κBp65, NLRP3, cleaved caspase-1, cleaved IL-1β, GluR and PSD95 in hippocampus were detected by western blot. The concentrations of IL-6 and TNF-α in hippocampus were determined by ELISA. The dendritic spine density was observed by Golgi-Cox staining. As a result, the treatment with DEO relieved anhedonia in SPT, reduced immobile duration in FST and TST. DEO treatment effectively attenuated the CUMS-caused alterations of TLR4, MyD88, TRAF6, p-NF-κBp65, NLRP3, cleaved caspase-1, cleaved IL-1β, GluR and PSD95. Furthermore, DEO could reduce the hippocampal inflammatory cytokine content and increase the density of dendritic spine. In conclusion, the present work indicated that DEO exhibited anti-depressant effect on CUMS-induced depressive mice, which was possibly due to the TLR4/NF-κB/NLRP3 pathway and the amelioration of dendritic spine density through GluR/PSD95 cascade. This article is protected by copyright. All rights reserved.