A20, as a downstream factor of Nrf2, is involved in the anti-neuroinflammatory and antidepressant-like effects of luteolin. (December 2022)

• Record Type: Journal Article
• Authors: Li, Zhipeng; Wang, Qingchen; Zhang, Zhonghong; Zhang, Xiao; Wu, Xintong; Li, Li; Zhang, Yi; Yu, Yihua
• Is Part Of: Journal of functional foods. Volume 99(2022)
• Publication Date: 2022-12
• Subjects: Neuroinflammation -- Depression -- Luteolin -- Microglia; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2022.105305
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Luteolin exerted anti-neuroinflammatory and antidepressant-like effects. Luteolin upregulated the expression of A20 and Nrf2. Upregulation of A20 and Nrf2 was involved in the inhibitory effects of luteolin on neuroinflammation. A20, as a downstream factor of Nrf2, was involved in the inhibitory effects of luteolin on activation of microglia. Abstract: Microglia-mediated neuroinflammation is closely related to depression. Many studies have shown that the NF-κB 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.