Bavachin exerted anti-neuroinflammatory effects by regulation of A20 ubiquitin-editing complex.

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-?B) 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-?B signaling pathway. Altogether, our results indicated that bavachin exerted anti-neuroinflammatory effects through inhibition of NF-?B 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.
Mesh Terms:
Animals, Anti-Inflammatory Agents, Cell Line, Cytokines, Flavonoids, Inflammasomes, Inflammation Mediators, Intracellular Signaling Peptides and Proteins, Mice, Microglia, NF-kappa B, NLR Family, Pyrin Domain-Containing 3 Protein, Neoplasm Proteins, Neuroinflammatory Diseases, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor alpha-Induced Protein 3, Ubiquitin, Ubiquitin-Protein Ligases, Up-Regulation
Int Immunopharmacol
Date: Nov. 01, 2021
Download Curated Data For This Publication
235022
Switch View:
  • Interactions 2