Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives.


:Chrysin, a natural flavone compound found in plants, has anti-inflammatory activity that has been previously explained in part by the suppression of promoter activities of pro-inflammatory enzymes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Here we present evidence that several chrysin derivatives modulate the activities, as well as the expression, of COX-2 and iNOS enzymes. Nitrate production triggered by lipopolysaccharide (LPS) was suppressed by treatment of cultured Raw264.7 cells (mice macrophage/monocyte) with chrysin, 5-hydroxy-7-methoxyflavone (Ch-2), and 5,7-diacetylflavone (Ch-4). Interestingly, COX-2 enzyme was strongly inhibited by Ch-4 (IC(50)=2.7 microM) but not by other derivatives. Furthermore, the inhibition of COX enzyme by Ch-4 was selective for COX-2 over COX-1. Three-dimensional modeling showed that Ch-4 fits well into the binding pocket of COX-2. The modeling suggested that a hydrogen bond exists between the oxygen of the ketone group at the 7-position of Ch-4 and the hydroxyl group of Tyr355. Docking Ch-4 into the V523I mutant of COX-2 indicated that Ile523 of COX-1 might contribute to the selectivity of COX-2 over COX-1. Ch-4 showed no effect on iNOS activity. Chrysin and Ch-2 weakly inhibited iNOS enzyme activity in the hemoglobin assay, but the underlying mechanisms of inhibition of iNOS by chrysin are not understood.


Pharmacol Res


Pharmacological research


Cho H,Yun CW,Park WK,Kong JY,Kim KS,Park Y,Lee S,Kim BK





Has Abstract


2004-01-01 00:00:00














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  • Sirt3 is a novel target to treat sepsis induced myocardial dysfunction by acetylated modulation of critical enzymes within cardiac tricarboxylic acid cycle.

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  • Antisense oligonucleotides as therapeutic agents.

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  • Direct inotropic effects of propofol and adenosine on rat atrial muscle: possible mechanisms.

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    authors: Cinel I,Gür S

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  • QiShenYiQi Pills® ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFβ1/Smads signaling pathway.

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    authors: Costa Queiroz RH,de Souza AM,Sampaio SV,Melchior E Jr

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    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Tonini M,Gatti G,Manzo L,Olibet G,Coccini T,Perucca E

    更新日期:1992-09-01 00:00:00