Flavone effects were assessed on soluble pro-inflammatory mediator (IL-8, IL-6, macrophage chemoattractant protein-1 (MCP-1), and cyclooxygenase-2 (COX-2)-derived PGE2) production and on nuclear factor (NF)-魏B activation in 3d-confluent and 21d-differentiated Caco-2 cells stimulated with interleukin (IL)-1尾.
Chrysin (CHRY) showed anti-inflammatory properties by decreasing COX-2-derived PGE2 and reducing NF-魏B activation. Compared to CHRY, the dimethoxylated form (CHRY-DM) significantly reduced the secretion of all pro-inflammatory mediators, except IL-8, at both cellular stages (P < 0.05); these effects being dose-dependent in 3d-cells. The reduction of NF-魏B activation was significantly more pronounced with CHRY-DM. By evaluating other flavones, it was established that several structural dispositions of flavones seemed to be determinant in order to attenuate the intestinal inflammatory response, such as methoxylation of the 5- and 7-hydroxyl groups on the A-ring, non-methoxylation of the 3鈥?hydroxyl groups on the B-ring, and methoxylation of the 3-hydroxyl group on the C-ring. Of all flavones examined, CHRY-DM exhibited the strongest anti-inflammatory activity.
These data indicate that, in the Caco-2 cell model, methoxylation of CHRY greatly improves its anti-inflammatory properties, probably through a more pronounced inhibition of the NF-魏B signaling pathway. Nevertheless, methoxylation of other flavones was not systematically beneficial.