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Bavachin exerted anti-neuroinflammatory effects by regulation of A20 ubiquitin-editing complex.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2021 Nov; Vol. 100, pp. 108085. Date of Electronic Publication: 2021 Aug 25. - Publication Year :
- 2021
-
Abstract
- Neuroinflammation is a major pathophysiological contributor to the progression of the central nervous system disorders. Bavachin is a natural product belonging to the flavonoid class. The anti-neuroinflammatory effect and the molecular mechanisms are not well understood. In this study, we found bavachin can exert anti-neuroinflammatory effect via inhibition of nuclear factor-kappa B (NF-κB) signaling. We found that bavachin can obviously upregulate the expression of A20 (TNFAIP3) in microglial cells. Further studies suggested siRNA-A20 knockdown treatment can attenuate the inhibitory effects of bavachin on neuroinflammation. We further found bavachin can increase the interaction of ubiquitin-editing enzyme A20 complex including A20, Tax1-binding protein 1 (TAX1BP1) and Itch, the subsequently downregulated the K63-ubiquitination of TNF receptor associated factor 6 (TRAF6) and NF-κB signaling pathway. Altogether, our results indicated that bavachin exerted anti-neuroinflammatory effects through inhibition of NF-κB signaling mediated by regulation of ubiquitin-editing enzyme A20 complex. Our finding has important clinical significance for the potential application of bavachin in the treatment of neurological disorders.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line
Cytokines metabolism
Inflammasomes metabolism
Inflammation Mediators metabolism
Intracellular Signaling Peptides and Proteins metabolism
Mice
Microglia enzymology
Microglia immunology
NF-kappa B genetics
NF-kappa B metabolism
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Neoplasm Proteins metabolism
Neuroinflammatory Diseases enzymology
Neuroinflammatory Diseases immunology
TNF Receptor-Associated Factor 6 metabolism
Tumor Necrosis Factor alpha-Induced Protein 3 genetics
Ubiquitin
Ubiquitin-Protein Ligases metabolism
Up-Regulation
Anti-Inflammatory Agents pharmacology
Flavonoids pharmacology
Microglia drug effects
Neuroinflammatory Diseases drug therapy
Tumor Necrosis Factor alpha-Induced Protein 3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 100
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34454289
- Full Text :
- https://doi.org/10.1016/j.intimp.2021.108085