Abstract
Increasing evidence suggests that inflammation is related to the pathophysiology of depression. Curcumin (CUR), which is a natural component extracted from the rhizome of Curcuma longa, seems to be efficacious in depression treatment. Hence, the present study aims to explore whether the anti-depressive effect of curcumin is connected to its anti-inflammatory features. Twenty-one SD rats were randomly divided into three groups, namely, control, CUMS (chronic unpredictable mild stress), and CUMS + CUR. After stress exposure for four weeks, the CUMS group showed depressive-like behaviors, and the curcumin treatment successfully corrected the depressive-like behaviors in stressed rats. Additionally, the curcumin could effectively decrease mRNA expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and suppress NF-κB activation. Curcumin also inhibited the stressed-induced P2X7R/NLRP3 inflammasome axis activation, along with the reduced transformation of pro-IL-1β to mature IL-1β. The stress-induced activation of indolamine-2, 3-dioxygenase (IDO) and an increased kynurenine/tryptophan ratio were also ameliorated by curcumin supplementation. In conclusion, the study revealed that curcumin relieves a depressive-like state through the inhibition of the NLRP3 inflammasome and kynurenine pathway.