The O-methylation of chrysin markedly improves its intestinal anti-inflammatory properties: Structure-activity relationships of flavones

被引:61
作者
During, Alexandrine [1 ]
Larondelle, Yvan [1 ]
机构
[1] UCLouvain, Inst Sci Vie, B-1348 Louvain, Belgium
关键词
Intestinal inflammation; Pro-inflammatory mediators; O-methylation; Flavones; Caco-2; cells; PROINFLAMMATORY CYTOKINES; DIETARY FLAVONOIDS; EPITHELIAL-CELLS; HYDROXYL GROUP; B-RING; INHIBITION; EXPRESSION; 5,7-DIMETHOXYFLAVONE; POLYPHENOLS; METHYLTRANSFERASE;
D O I
10.1016/j.bcp.2013.10.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to investigate whether methoxylated flavones versus their unmethylated analogs can modulate the intestinal inflammatory response. 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 PGE(2)) production and on nuclear factor (NF)kappa B activation in 3d-confluent and 21d-differentiated Caco-2 cells stimulated with interleukin (IL)-1 beta. Chrysin (CHRY) showed anti-inflammatory properties by decreasing COX-2-derived PGE2 and reducing NF-kappa 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-kappa 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'-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-kappa B signaling pathway. Nevertheless, methoxylation of other flavones was not systematically beneficial. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:1739 / 1746
页数:8
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