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A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis


Liew, Choi Yi and Tham, Chau Ling and Lam, Kok Wai and Tengku Mohamad, Tengku Azam Shah and Kim, Min Kyu and Cheah, Yoke Kqueen and Zakaria, Zainul Amiruddin and Sulaiman, Mohd Roslan and Lajis, Md Nordin and Israf Ali, Daud Ahmad (2010) A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis. Immunopharmacology and Immunotoxicology, 32 (3). pp. 495-509. ISSN 0892-3973; ESSN: 1532-2513


HMP [3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone] was evaluated for its ability to inhibit the synthesis of major proinflammatory mediators and cytokines in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells and phorbol myristate acetate (PMA)-differentiated/LPS-induced U937 cells. HMP suppressed the production of nitric oxide (NO) with significant inhibitory effects at doses as low as 0.78 microM (P < 0.05). Prostaglandin E2 (PGE2) secretion was also inhibited at doses of 12.5 microM and above (P < 0.01). The secretion of both TNF-alpha and IL-6 were only inhibited at the highest dose used (25 microM; P < 0.001). IL-1beta secretion was also inhibited from 12.5 microM onwards (P < 0.01). This inhibition was demonstrated to be caused by down-regulation of inducible enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), without direct effect upon iNOS or COX-2 enzyme activity. HMP only inhibited iNOS (P < 0.001) and IL-1beta (P < 0.05) gene expression at the highest tested concentration. HMP did not affect the secretion of chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10. The most striking effect of HMP was its NO inhibitory activity and therefore we conclude that HMP is a selective inhibitor of iNOS.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Medicine and Health Science
Institute of Bioscience
DOI Number: https://doi.org/10.3109/08923970903575708
Publisher: Informa Healthcare
Keywords: COX-2; Cytokines; Hydroxypropenone; INOS; RAW 264.7; U937
Depositing User: Nurul Ainie Mokhtar
Date Deposited: 05 Jun 2015 13:06
Last Modified: 05 Oct 2015 03:10
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.3109/08923970903575708
URI: http://psasir.upm.edu.my/id/eprint/12887
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