LAUSR

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‐&kgr;B 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. HighlightsPerilla aldehyde attenuates CUMS‐induced depressive‐like behaviors.Perilla aldehyde inhibited the NLRP3 inflammasome activation through the upregulation of TRX.The antidepressant‐like effects of perilla aldehyde are regulated via TXNIP/TRX/NLRP3 pathway in rats.