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.
 
 
 
Highlights
Depression, a condition of mental disturbance, represents a series of presentations characterized by physical, emotional, and related cognitive disorders [1]
Oridonin and fluoxetine reversed the effects of chronic unpredictable mild stress (CUMS) treatment (p < 0.01 vs. CUMS), and the number of events in the fluoxetine group was closer to that of control (Figure 2)
The effects of oridonin on motivational behavior were analyzed using the sucrose preference test (SPT), TST, and forced swim test (FST)
Summary
Depression, a condition of mental disturbance, represents a series of presentations characterized by physical, emotional, and related cognitive disorders [1]. Chronic stress is a primary factor of depression, the cause of which is immune disorders and inflammation [3]. Increasing evidence has shown that the elevated expression of TXNIP is related to chronic stress and depression, and TXNIP deficiency inhibits inflammatory responses [7]. Oridonin (Figure 1A), a natural bioactive tetracycline diterpenoid, is a flavonoid compound isolated from Rabdosia rubescens that was first identified as an antitumor compound [8] It has attracted increased attention because of its various pharmacological effects, including antiinflammatory and anti-oxidant activities [9]. Few studies have reported the effects of oridonin on depressive behaviors caused by chronic stress, and the relevant molecular mechanism requires further study. The present study aimed to investigate the effects of oridonin on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and determine the mechanism. All the data were shown as means ± standard deviation (SD) and analyzed using one-way analysis of variance (ANOVA) with Tukey’s multiple comparison test as the post hoc test. p < 0.05 was considered statistically significant
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