Perilla aldehyde attenuates CUMS-induced depressive-like behaviors via regulating TXNIP/TRX/NLRP3 pathway in rats

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). 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. 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. 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. •Perilla 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.