Nomilin Alleviates Neuroinflammation and Depressive-like Behaviors in Mice through the Upregulation of TAX1BP1-Mediated Modulation of Microglia Polarization

Nomilin is a limonoid compound that is found in citrus fruits. However, their functions remain to be further studied. The present study mainly analyzed the antineuroinflammation and antidepressive function of nomilin. The antidepressant and antineuroinflammatory effects of nomilin were examined in a mouse model induced by lipopolysaccharide (LPS), and the regulation of nomilin on the BV2 model induced by LPS was examined. The study found that nomilin exhibited a good antidepressant effect. We further found that nomilin inhibited the activation of the NF-κB pathway and upregulated the expression of TAX1BP1, and subsequently, the M1 phenotype of microglia was inhibited and the M2 phenotype of microglia was promoted. The results also indicated that nomilin attenuated neuronal damage and synaptic defects and protected the blood-brain barrier through inhibition of neuroinflammation. In summary, the present study, it was clarified that nomilin may regulate the microglia polarization by upregulation of TAX1BP1 and inhibition of the NF-κB pathway, thus exerting antineuroinflammatory as well as antidepressant effects. Therefore, nomilin derived from citrus fruits has application potential in the treatment of depression.