Safflower Extract Improves Depression in Mice by Inhibiting the TLR4-NLRP3 Inflammation Signaling Pathway

BACKGROUND:Safflower extract (SE) improves depression in mice by inhibiting the TLR4-NLRP3 inflammatory signaling pathway.METHODS:Chronic unpredictable mild stress (CUMS) was used to establish a mouse model of depression. A total of 60 adult male ICR mice were randomly divided into 6 groups: control group, depression group (CUMS only), SE (10 mg/kg) + depression group (CUMS+SE, 10 mg/kg), SE (30 mg/kg) + depression group (CUMS+SE, 30 mg/kg), Cli-095 + depression group (CUMS+Cli-95), and fluoxetine hydrochloride (FLU) + depression group (CUMS+FLU). We assessed the depressive behaviors of these mice using the sucrose preference test (SPT), the open field test (OFT), the forced swim test (FST), and the tail suspension test (TST). We measured the expression levels of SOD, MDA, GSH-Px, 5-HT, NE, TNF-α, IL-1β, and IL-6 using ELISA kits. Western blot was used to determine the relative expression levels of TLR4, p38, NF-κB, NLRP3, and caspase-1.RESULTS:SE significantly improved the results of the SPT, OFT, FST, and TST. SE also increased the expression levels of 5-HT and NE in the prefrontal cortex while decreased the expression levels of TNF-α, IL-1β, and IL-6 compared with CUMS. SE (10 or 30 mg/kg) or FLU (10 mg/kg) significantly inhibited the expression of TLR4 and p-p38 induced by CUMS. SE significantly inhibited the expression of p-NF-κB in the prefrontal cortex and hippocampus induced by CUMS. The decrease of NLRP3 and caspase-1 were obviously reversed after administration of SE (10 or 30 mg/kg) or FLU (10 mg/kg).CONCLUSIONS:The results showed that SE has potential antidepressant effects in CUMS mice, and its underlying mechanism may be related to its effects on inflammation and the TLR4-NF-κB-NLRP3 signaling pathway in the brain.