Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and whole blood

Ahmad, Syahida and Israf Ali, Daud Ahmad and Lajis, Md Nordin and Shaari, Khozirah and Mohamed, Habsah and Abdul Wahab, Afiza and Tajul Arifin, Khaizurin and Wei, Yee Ho and Abdul Aziz, Nasaruddin and Abdul Kadir, Arifah and R. Sulaiman, Mohamad and Somchit, Muhammad Nazrul (2006) Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and whole blood. European Journal of Pharmacology, 538 (1-3). pp. 188-194. ISSN 0014-2999

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Official URL: http://dx.doi.org/10.1016/j.ejphar.2006.03.070

Abstract

Some chalcones, such as hydroxychalcones have been reported previously to inhibit major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and reactive oxygen species production by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of critical transcription factors. In this report, the effects of cardamonin (2′,4′-dihydroxy-6′-methoxychalcone), a chalcone that we have previously isolated from Alpinia rafflesiana, was evaluated upon two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds namely RAW 264.7 cells and whole blood. Cardamonin inhibited NO and PGE2 production from lipopolysaccharide- and interferon-γ-induced RAW cells and whole blood with IC50 values of 11.4 μM and 26.8 μM, respectively. Analysis of thromboxane B2 (TxB2) secretion from whole blood either stimulated via the COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB2 via both pathways with IC50 values of 2.9 and 1.1 μM, respectively. Analysis of IC50 ratios determined that cardamonin was more COX-2 selective in its inhibition of TxB2 with a ratio of 0.39. Cardamonin also inhibited the generation of intracellular reactive oxygen species and secretion of TNF-α from RAW 264.7 cells in a dose responsive manner with IC50 values of 12.8 μM and 4.6 μM, respectively. However, cardamonin was a moderate inhibitor of lipoxygenase activity when tested in an enzymatic assay system, in which not a single concentration tested was able to cause an inhibition of more than 50%. Our results suggest that cardamonin acts upon major pro-inflammatory mediators in a similar fashion as described by previous work on other closely related synthetic hydroxychalcones and strengthens the conclusion of the importance of the methoxyl moiety substitution on the 4′ or 6′ locations of the A benzene ring.

Item Type:Article
Keyword:Cardamonin, Alpinia rafflesiana, RAW 264.7, Whole blood, Inflammatory mediator
Faculty or Institute:Faculty of Veterinary Medicine
Publisher:Elsevier B.V.
DOI Number:10.1016/j.ejphar.2006.03.070
Altmetrics:http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1016/j.ejphar.2006.03.070
ID Code:7884
Deposited By: Azizan Arshad
Deposited On:29 Sep 2010 07:22
Last Modified:29 Sep 2010 07:26

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