Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China.
Biotechnol Appl Biochem. 2021 Feb;68(1):52-59. doi: 10.1002/bab.1893. Epub 2020 Feb 7.
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.
本研究旨在评估五味子丙素（DEO）对慢性不可预测轻度应激（CUMS）诱导的小鼠的抗抑郁作用。小鼠接受 CUMS 模型 8 周。从第 6 周开始，小鼠每天经胃内给予 DEO 治疗，连续 3 周。进行行为测试，包括蔗糖偏好测试（SPT）、强迫游泳测试（FST）、悬尾测试（TST）和旷场测试。此外，通过 Western blot 检测海马体中 TLR4、MyD88、TRAF6、p-NF-κBp65、NLRP3、cleaved caspase-1、cleaved IL-1β、GluR 和 PSD95 的表达。通过酶联免疫吸附试验（ELISA）测定海马体中 IL-6 和 TNF-α的浓度。通过高尔基-考克斯染色观察树突棘密度。结果，DEO 治疗缓解了 SPT 中的快感缺失，并减少了 FST 和 TST 中的不动时间。DEO 治疗有效减轻了 CUMS 引起的 TLR4、MyD88、TRAF6、p-NF-κBp65、NLRP3、cleaved caspase-1、cleaved IL-1β、GluR 和 PSD95 的改变。此外，DEO 可降低海马体炎性细胞因子含量并增加树突棘密度。总之，本研究表明 DEO 对 CUMS 诱导的抑郁小鼠具有抗抑郁作用，这可能是通过 TLR4/NF-κB/NLRP3 途径以及通过 GluR/PSD95 级联改善树突棘密度实现的。
