Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Oridonin ameliorates depressive-like behaviors induced by chronic unpredictable mild stress in mice via TXNIP/NLRP3 signaling pathway

Lina Wang , Ziye Huang, Jing Ping, XingYan Liu, Ziyao Cai, Chenghao Dai

Department of Psychiatry, Whenzhou No. 7 People's Hospital, Wenzhou City, Zhejiang Province 325000, China;

For correspondence:- Lina Wang Email: linawang2082@163.com Tel:+8657789870026

Accepted: 8 March 2021 Published: 31 March 2021

Citation: Wang L, Huang Z, Ping J, Liu X, Cai Z, Dai C. Oridonin ameliorates depressive-like behaviors induced by chronic unpredictable mild stress in mice via TXNIP/NLRP3 signaling pathway. Trop J Pharm Res 2021; 20(3):531-536 doi: 10.4314/tjpr.v20i3.13

© 2021 The authors.
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Abstract

Purpose: To investigate the effect and mechanism of oridonin in chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors.

Methods: CUMS was established using 6-week stress stimuli, including feed/water deprivation, night lighting, inverted light/dark cycle, and tail clamping. Depressive behaviors were analyzed using the sucrose preference test, forced swim test (FST), and tail suspension test (TST). Locomotor activity was analyzed using the open field test (OFT) while inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. The activation of the TXNIP/NLRP3 signaling pathway was evaluated by western blot.

Results: Sucrose consumption of CUMS-treated mice was significantly decreased, while immobility times of the FST (control vs. CUMS, ~50 to 150 s; p < 0.01) and TST (Control vs. CUMS, ~50 to 130 s; p < 0.01) were increased; oridonin significantly reversed these effects. Spontaneous locomotor activities (crossing, rearing, and grooming) measured in the OFT were decreased after the CUMS procedure, and oridonin increased these activities (p < 0.01 vs. CUMS). Oridonin decreased the production of tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1 in the hippocampus of CUMS-treated mice and significantly inhibited activation of the TXNIP/NLRP3 pathway induced by CUMS.

Conclusion: Oridonin ameliorates depressive-like behaviors in mice induced by CUMS, partly via TXNIP/NLRP3 signaling pathway. Thus, the findings provide evidence for the potential application of oridonin in depression therapy.

Keywords: Oridonin, Depression, Chronic unpredictable mild stress, TXNIP/NLRP3 signaling pathway