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

Abstract

The purpose of the present study was to evaluate the antidepressant 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), and open field test 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 enzyme linked immune sorbent assay (ELISA). The dendritic spine density was observed by Golgi-Cox staining. As a result, the treatment with DEO relieved anhedonia in SPT, and 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 antidepressant effect on CUMS-induced depressive mice, which was possible due to the TLR4/NF-κB/NLRP3 pathway and the amelioration of dendritic spine density through GluR/PSD95 cascade.