title: Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and whole blood.
abstract: Some chalcones, such as hydroxychalcones have been reported previously to inhibit major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) 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 PGE(2) production from lipopolysaccharide- and interferon-gamma-induced RAW cells and whole blood with IC(50) values of 11.4 microM and 26.8 microM, respectively. Analysis of thromboxane B(2) (TxB(2)) secretion from whole blood either stimulated via the COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB(2) via both pathways with IC(50) values of 2.9 and 1.1 microM, respectively. Analysis of IC(50) ratios determined that cardamonin was more COX-2 selective in its inhibition of TxB(2) with a ratio of 0.39. Cardamonin also inhibited the generation of intracellular reactive oxygen species and secretion of TNF-alpha from RAW 264.7 cells in a dose responsive manner with IC(50) values of 12.8 microM and 4.6 microM, 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.
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Malaysia.
authors.forename: Syahida
authors.initials: S
authors.lastname: Ahmad
authors.forename: Daud A
authors.initials: DA
authors.lastname: Israf
authors.forename: Nordin Hj
authors.initials: NH
authors.lastname: Lajis
authors.forename: Khozirah
authors.initials: K
authors.lastname: Shaari
authors.forename: Habsah
authors.initials: H
authors.lastname: Mohamed
authors.forename: Afiza A
authors.initials: AA
authors.lastname: Wahab
authors.forename: Khaizurin T
authors.initials: KT
authors.lastname: Ariffin
authors.forename: Wei Yee
authors.initials: WY
authors.lastname: Hoo
authors.forename: Nasaruddin A
authors.initials: NA
authors.lastname: Aziz
authors.forename: Arifah A
authors.initials: AA
authors.lastname: Kadir
authors.forename: Mohamad R
authors.initials: MR
authors.lastname: Sulaiman
authors.forename: Muhammad N
authors.initials: MN
authors.lastname: Somchit
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D047188:Chalcones; D005419:Flavonoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013929:Thromboxane B2; D007371:Interferon-gamma; D008084:Lipoxygenase; C436747:cardamonin; D015232:Dinoprostone