title: A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis.
abstract: 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.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
authors.forename: Choi Yi
authors.initials: CY
authors.lastname: Liew
authors.forename: Chau Ling
authors.initials: CL
authors.lastname: Tham
authors.forename: Kok Wai
authors.initials: KW
authors.lastname: Lam
authors.forename: Azam Shah
authors.initials: AS
authors.lastname: Mohamad
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Kim
authors.forename: Yoke Kqueen
authors.initials: YK
authors.lastname: Cheah
authors.forename: Zainul Amiruddin
authors.initials: ZA
authors.lastname: Zakaria
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
authors.forename: Md Nordin
authors.initials: MN
authors.lastname: Lajis
authors.forename: Daud Ahmad
authors.initials: DA
authors.lastname: Israf
mesh_terms: D000818:Animals; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D011427:Propiophenones / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020298:U937 Cells; D000093242:Interleukin-6 Inhibitors
chemical_list: D047188:Chalcones; D051546:Cyclooxygenase 2; D016207:Cytokines; D015232:Dinoprostone; D005663:Furans; D016898:Interferon-alpha; D007371:Interferon-gamma; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011427:Propiophenones; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C553916:3-(2-hydroxyphenyl)-1-(5-methylfuran-2-yl)propenone