The O-methylation of chrysin markedly improves its intestinal anti-inflammatory properties: Structure-activity relationships of flavones
(2013) Biochemical Pharmacology — Vol. 86, n° 12, p. 1739-1746 (2013)
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- 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)-κB activation in 3d-confluent and 21d-differentiated Caco-2 cells stimulated with interleukin (IL)-1β. Chrysin (CHRY) showed anti-inflammatory properties by decreasing COX-2-derived PGE2 and reducing NF-κB 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-κB 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-κB signaling pathway. Nevertheless, methoxylation of other flavones was not systematically beneficial. Chemical compounds studied in this article*Chrysin (PubChem CID 5281607)*5,7-dimethoxyflavone (PubChem CID 88881)*3′,4′- dihydroxyflavone (PubChem CID 145726)*3′,4′-dimethoxyflavone (PubChem CID 688674)*apigenin (PubChem CID 5280443)*4′,5,7- trimethoxyflavone (PubChem CID 79730)*luteolin (PubChem CID 5280445)*3′,4′,5,7-tetramethoxyflavone (PubChem CID 631170)*quercetin (PubChem CID 5280343)*3′,4′,3,5,7- pentamethoxyflavone (PubChem CID 97332) Abbreviations*API*apigenin or 4′,5,7-trihydroxyflavone*API-TM*4′,5,7- trimethoxyflavone*CHRY*chrysin or 5,7-dihydroxyflavone*CHRY- DM*dimethylated chrysin or 5,7-dimethoxyflavone*COMT*catechol- O-methyltransferase*COX*cyclooxygenase*CTL* control*3′,4′-DHF*3′,4′- dihydroxyflavone*3′,4′-DMF*3′,4′- dimethoxyflavone*DSS*dextran sodium sulfate*FBS*fetal bovine serum*IBDs*intestinal bowel diseases*IL* interleukin*LDH*lactate dehydrogenase*IECs*intestinal epithelial cells*iNOS*inducible nitric oxide synthase* LPS*lipopolysaccharide*LUT*luteolin or 3′,4′,5,7- tetrahydroxyflavone*LUT-QM*3′,4′,5,7- tetramethoxyflavone*MCP-1*monocyte chemotactic protein- 1*NEAA*nonessential amino acids*NF-κB*nuclear factor κB*QUER*quercetin or 3′,4′,3,5,7- pentahydroxyflavone*QUER-PM*3′,4′,3,5, 7-pentamethoxyflavone. © 2013 Elsevier Inc. All rights reserved.
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During, A., & Larondelle, Y. (2013). The O-methylation of chrysin markedly improves its intestinal anti-inflammatory properties: Structure-activity relationships of flavones. Biochemical Pharmacology, 86(12), 1739-1746. https://doi.org/10.1016/j.bcp.2013.10.003 (Original work published 2013)