Suppression of TNFα-mediated NFκB activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells

Flavonoids are a group of naturally-occurring phenolic compounds in the plant kingdom, and many flavonoids are found with vascular protective properties. Nevertheless how the protective response is exerted by flavonoids is not well characterized. In view of the nuclear factor-κB (NFκB) may play a central role in the initiation of atherosclerosis, prevention of the activation of NFκB represents an important role in protecting vascular injury. In this study, the effects of flavonoids on NFκB/inhibitor-κB (IκB) system in ECV304 cells activated with tumor necrosis factor-α (TNFα) were examined. We investigated the inhibitory action of six flavonoids on IκB kinase (IKK) activity, an enzyme recently found to phosphorylate critical serine residues of IκB for degradation. Of six flavonoids tested, myricetin was found to strongly inhibit IKK kinase activity, and prevent the degradation of IκBα and IκBβ in activated endothelial cells. Furthermore, myricetin was also found to inhibit NFκB activity correlated with suppression of monocyte adhesion to ECV304 cells. Therefore we conclude that flavonoids may be of therapeutic value for vascular disease through down regulation of NFκB/IκB system.