A20, as a downstream factor of Nrf2, is involved in the anti-neuroinflammatory and antidepressant-like effects of luteolin

Microglia-mediated neuroinflammation is closely related to depression. Many studies have shown that the NF-KB pathway was involved in the anti-neuroinflammatory effects of luteolin. However, more detailed molecular mechanisms should be further studied. In this study, our data indicated that luteolin inhibited neuroinflammation and alleviated depression-like behavior in a lipopolysaccharide (LPS)-induced mouse model. Further investigation revealed that luteolin increased the expression of A20 and Nrf2 and decreased the expression of TRAF6 while removing K63-linked polyubiquitin chains from TRAF6. Knockdown treatment using siRNA-A20 or Nrf2 reversed the effects of luteolin on neuroinflammation. This study explored the novel mechanism by which luteolin exerted anti-neuroinflammatory and antidepressant-like effects in a lipopolysaccharide-induced mouse model, which might be related to the upregulation of A20 and Nrf2. Notably, A20 exerted its function as a downstream factor of Nrf2. This study provides evidence for the potential application of luteolin in the prevention and treatment of neuroinflammation and depression.

Automated summary

Luteolin inhibits neuroinflammation and alleviates depression-like behavior by upregulating A20 and Nrf2.