Baicalein inhibits TNF-α-induced NF-κB activation and expression of NF-κB-regulated target gene products

The nuclear factor-alpha (NF-kappa B) transcription factors control many physiological processes including inflammation, immunity, apoptosis and angiogenesis. In our search for NF-kappa B inhibitors from natural resources, we identified baicalein from Scutellaria baicalensis as an inhibitor of NF-kappa B activation. As examined by the NF-kappa B luciferase reporter assay, we found that baicalein suppressed TNF-alpha-induced NE-kappa B activation in a dose-dependent manner. It also inhibited TNF-alpha-induced nuclear translocation of p65 through inhibition of phosphorylation and degradation of I kappa B alpha. Furthermore, baicalein blocked the TNF-alpha-induced expression of NF-kappa B target genes involved in anti-apoptosis (cIAP-1, cIAP-2, FLIP and BCL-2), proliferation (COX-2, cyclin D1 and c-Myc), invasion (MMP-9), angiogenesis (VEGF) and major inflammatory cytokines (IL-8 and MCP1). The flow cytometric analysis indicated that baicalein potentiated TNF-alpha-induced apoptosis and induced G1 phase arrest in HeLa cells. Moreover, baicalein significantly blocked activation of p38, extracellular signal-regulated kinase 1/2 (ERK1/2). Our results imply that baicalein could be a lead compound for the modulation of inflammatory diseases as well as certain cancers in which inhibition of NF-kappa B activity may be desirable.