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

详细信息    查看全文

• 作者：Alex ; rine During ; Yvan Larondelle
• 关键词：Chrysin (PubChem CID 5281607) ; 5 ; 7-dimethoxyflavone (PubChem CID 88881) ; 3&prime ; 4&prime ; -dihydroxyflavone (PubChem CID 145726) ; 3&prime ; 4&prime ; -dimethoxyflavone (PubChem CID 688674) ; apigenin (PubChem CID 5280443) ; 4&prime ; 5 ; 7-trimethoxyflavone (PubChem CID 79730) ; luteolin (PubChem CID 5280445) ; 3&prime ; 4&prime ; 5 ; 7-tetramethoxyflavone (PubChem CID 631170) ; quercetin (PubChem CID 5280343) ; 3&prime ; 4&prime ; 3 ; 5 ; 7-pentamethoxyflavone (PubChem CID 97332)
• 刊名：Biochemical Pharmacology
• 出版年：15 December, 2013
• 年：2013
• 卷：86
• 期：12
• 页码：1739-1746
• 全文大小：591 K

文摘

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 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.