Fig. 6.

Schematic of mechanism of action of delphinidin on NF-κB pathway and COX-2 expression in human chondrocytes.

Upon binding of IL-1 to IL-1RI a multiprotein complex involving IL-1RI/IRAK1/IRAK2/IL-1RAcp/MyD88 is formed. TRAF6 is recruited to the complex and activates NIK, which in turn activates the IKK complex. Activated IKK complex phosphorylates IκB, which is degraded by proteosome resulting in the release and translocation of NF-κB to the nucleus and subsequent transcription of COX-2. Elevated level of COX-2 result in production and release of PGE₂ from the chondrocytes. Delphinidin blocks the process by inhibiting the phosphorylation of IRAK and NIK as well as by inhibiting the expression of IKKβ resulting in the inhibition of COX-2 expression and production of PGE₂.