Baicalein suppresses LPS-induced inflammation by modulating nucleocytoplasmic transport of NF-κB p65 in macrophages

Inflammation is a common physiological process during the immune response.Dysregulated inflammation results in damage to our body.Baicalein (BAI) possesses anti-inflammatory activities, while the underlying mechanisms are still elusive.NF-κB, translocating into nuclear in an importin β-dependent manner, plays an important role in the production of pro-inflammatory cytokines in macrophages.We speculate that importin β1 (Impβ1) might mediate the inhibitory effect of BAI on inflammation.In lipopolysaccharide (LPS)-stimulated macrophages Ana-1 and RAW264.7,BAI treatment significantly decreased the production of pro-inflammatory cytokines such as TNF-α, IL-6, MCP-1, and NO.Notably, expression downregulation using siRNA or function inhibition using importazole (IPZ) of Impβ1 could also suppress the production of pro-inflammatory cytokines induced by LPS.Further mechanistic studies revealed that BAI inhibits nuclear translocation of NF-κB p65 by interfering with the interaction between NF-κB p65 and Impβ1.In conclusion, our findings provide new evidence that BAI inhibited inflammatory responses in macrophages by suppressing nuclear import of NF-κB via Impβ1-dependent mechanisms.