Chrysin alleviated CUMS-induced depressive-like behaviors in mice via directly targeting Fyn

Neuroinflammation is the common pathological feature of neuropsychiatric diseases. Chrysin, a kind of natural flavonoid compound, was reported to exert antidepressant effects, however the direct targets of chrysin remain unclear. Currently studies showed chrysin alleviated CUMS-induced depressive-like behaviors in mice. We found chrysin inhibited CUMS-induced microglia activation in mice. We further found that chrysin inhibited the activation of Fyn and NF-?B pathway, and decreased the expression of iNOS, COX2 and NLRP3. Furthermore, our data showed that chrysin can bind to Fyn using pull-down assay. Transfection siRNA-Fyn abolished the inhibitory effect of chrysin on activation of NF-?B pathway. This study revealed that targeting inhibition of Fyn by chrysin to alleviate CUMS-induced neuroinflammation and depressive-like behaviors via inhibiting the expression of iNOS, COX2 and NLRP3 mediated by inhibition of NF-?B pathway. Thus, this study has revealed, for the first time, Fyn was the direct target of chrysin against neuroinflammation and neuroinflammation-related depression.