Microglia-mediated neuroinflammation is associated with a variety of disorders, including depression. Bavachalcone is a natural ingredient extracted from Psoralea corylifolia and has various pharmacological effects. However, its anti-neuroinflammatory and antidepressant effects remain unclear. In the present study, we found that bavachalcone improved lipopolysaccharide-induced depressive-like behaviors in mice and exerted an inhibitory effect on the activation of microglia in brain tissue. Further study revealed that bavachalcone inhibited the expression of TRAF6 and the activation of the NF-κB pathway in lipopolysaccharide-induced in vitro and vivo models, while bavachalcone upregulated the expression of A20 and TAX1BP1 and enhanced their interactions. In addition, bavachalcone inhibited the production of pro-inflammatory cytokines TNF-α and IL-6. Transfection with siRNA treatment showed that downregulation of A20 and TAX1BP1 weakened the anti-neuroinflammatory effect of bavachalcone. In conclusion, these results are the first to demonstrate that bavachalcone exerts anti-neuroinflammatory and antidepressant effects via inhibition of the NF-κB pathway mediated by upregulating A20 and TAX1BP1, and may be a potential candidate for the treatment of neuroinflammation-related diseases, including depression.
Keywords: A20; Bavachalcone; Depression; Neuroinflammation; TAX1BP1.
Copyright © 2023 Elsevier B.V. All rights reserved.