title: Dimethoxycurcumin, a synthetic curcumin analogue with higher metabolic stability, inhibits NO production, inducible NO synthase expression and NF-kappaB activation in RAW264.7 macrophages activated with LPS.
abstract: Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) in activated macrophages is linked to acute and chronic inflammation. Thus, it would be valuable to develop inhibitors of NO and/or iNOS for potential therapeutic use. We investigated whether dimethoxycurcumin (DiMC), a synthetic curcumin analogue with higher metabolic stability over curcumin, could inhibit NO production and iNOS expression in activated macrophages. RAW264.7 macrophages were activated with lipopolysaccharide (LPS) in the absence or presence of DiMC, which contains four methoxy groups at two aromatic rings, curcumin containing two, bis-demethoxycurcumin (BDMC) containing none, or tetrahydrocurcumin (THC) containing two but lacking conjugated double bonds in the central seven-carbon chain. NO production, iNOS expression and NF-kappaB activity were examined. DiMC, curcumin and BDMC inhibited NO production, iNOS expression and NF-kappaB activation, with DiMC being the most effective, followed by curcumin and BDMC. THC failed to inhibit NO production, iNOS expression and NF-kappaB activation. Our results suggest that DiMC inhibits NO production, iNOS expression and NF-kappaB activation in LPS-activated macrophages, which may be due not only to the conjugated double bonds but also the increased number of methoxy groups.
authors.affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Jeonbuk, Republic of Korea. Fax: +82-63-851-5066.
authors.forename: Hyun-Ock
authors.initials: HO
authors.lastname: Pae
authors.forename: Sun-Oh
authors.initials: SO
authors.lastname: Jeong
authors.forename: Hak Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Seong Heak
authors.initials: SH
authors.lastname: Kim
authors.forename: Yung Sun
authors.initials: YS
authors.lastname: Song
authors.forename: Sung-kwun
authors.initials: SK
authors.lastname: Kim
authors.forename: Kyu-Yun
authors.initials: KY
authors.lastname: Chai
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004355:Drug Stability; D051550:I-kappa B Kinase / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics*; D018517:Plant Roots / Q000737:chemistry
chemical_list: D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C521105:dimethoxycurcumin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051550:I-kappa B Kinase; D003474:Curcumin