Perilla aldehyde attenuates CUMS-induced depressive-like behaviors via regulating TXNIP/TRX/NLRP3 pathway in rats.
BACKGROUND
Current evidence supports that inflammatory reaction in the hippocampus is a potential cause of major depressive disorder (MDD). Perilla aldehyde (PAH), a major constituent from Perilla frutescens, has been reported to have anti-inflammatory and anti-oxidant activity. The aim of this study is to explore the antidepressant-like effect and the underlying mechanism of PAH on the rats model induced by chronic unpredictable mild stress (CUMS).


METHODS
CUMS rats model was built to tested their depressive-like behaviors. The levels of pro-inflammatory cytokines were tested. Proteins were analyzed by Western blot and Immunohistochemistry.


RESULTS
We found that treatment with PAH (20, 40 mg/kg) and fluoxetine (FLU, 10 mg/kg) significantly improved the sucrose consumption, immobility time in forced swim test (FST), as well as locomotor activity in open-field test (OFT). The levels of pro-inflammatory cytokines in hippocampus were also suppressed effectively by PAH and FLU administration. Western blot analysis showed the up-regulated levels of TXNIP, NLRP3, Cleaved caspase-1 and p-NF-κB p65 in the hippocampus in rats exposed to CUMS paradigm, while different degrees of down-regulation in their expression were detected after PAH (20, 40 mg/kg) and FLU (10 mg/kg) treatment respectively. The results from histopathological examination further demonstrated that PAH (20, 40 mg/kg) and FLU (10 mg/kg) treatment reversed the alteration of TRX, NLRP3 and Cleaved caspase-1 induced by CUMS procedure.


CONCLUSIONS
Our results demonstrated that PAH exhibited antidepressant-like effect in CUMS-induced rats model of depression, which might be mediated by TXNIP/TRX/NLRP3 pathway.
['Song|Yichen|Y|', 'Sun|Ruoxi|R|', 'Ji|Zhouye|Z|', 'Li|Xiaoxi|X|', 'Fu|Qiang|Q|', 'Ma|Shiping|S|']
D000818:Animals D018687:Antidepressive Agents, Second-Generation D002352:Carrier Proteins D061945:Caspase Inhibitors D018797:Cell Cycle Proteins D002908:Chronic Disease D016207:Cytokines D003863:Depression D005473:Fluoxetine D006624:Hippocampus D007249:Inflammation D008297:Male D039821:Monoterpenes D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D031343:Perilla D051381:Rats D017207:Rats, Sprague-Dawley D015398:Signal Transduction D013315:Stress, Psychological D013550:Swimming D013879:Thioredoxins
Perilla aldehyde TXNIP/TRX/NLRP3 Depression Inflammation