Selective inhibition of NF-κB activation by the flavonoid hepatoprotector silymarin in HepG2 -: Evidence for different activating pathways

The bioflavonoid silymarin is found to potently suppress both nuclear factor kappa-B (NF-kappa B)-DNA binding activity and its dependent gene expression induced by okadaic acid in the hepatoma cell line HepG2. Surprisingly, tumor necrosis factor-alpha-induced NF-kappa B activation was not affected by silymarin, thus demonstrating a pathway-dependent inhibition by silymarin. Many genes encoding the proteins of the hepatic acute phase response are under the control of the transcription factor NF-kappa B, a key regulator in the inflammatory and immune reactions. Thus, the inhibitory effect of silymarin on NF-kappa B activation could be involved in its hepatoprotective property. (C) 1998 Federation of European Biochemical Societies.