title: A curcumin derivative, 2,6-bis(2,5-dimethoxybenzylidene)-cyclohexanone (BDMC33) attenuates prostaglandin E2 synthesis via selective suppression of cyclooxygenase-2 in IFN-γ/LPS-stimulated macrophages.
abstract: Our preliminary screening had shown that the curcumin derivative [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] or BDMC33 exhibited improved anti-inflammatory activity by inhibiting nitric oxide synthesis in activated macrophage cells. In this study, we further investigated the anti-inflammatory properties of BDMC33 on PGE(2 )synthesis and cyclooxygenase (COX) expression in IFN-γ/LPS-stimulated macrophages. We found that BDMC33 significantly inhibited PGE(2) synthesis in a concentration-dependent manner albeit at a low inhibition level with an IC(50) value of 47.33 ± 1.00 µM. Interestingly, the PGE(2) inhibitory activity of BDMC33 is not attributed to inhibition of the COX enzyme activities, but rather BDMC33 selectively down-regulated the expression of COX-2. In addition, BDMC33 modulates the COX expression by sustaining the constitutively COX-1 expression in IFN-γ/LPS-treated macrophage cells. Collectively, the experimental data suggest an immunodulatory action of BDMC33 on PGE(2) synthesis and COX expression, making it a possible treatment for inflammatory disorders with minimal gastrointestinal-related side effects.
authors: Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. heng1011@yahoo.co.uk
authors: Ka-Heng
authors: KH
authors: Lee
authors: Faridah
authors: F
authors: Abas
authors: Noorjahan Banu Mohamed
authors: NB
authors: Alitheen
authors: Khozirah
authors: K
authors: Shaari
authors: Nordin Haji
authors: NH
authors: Lajis
authors: Syahida
authors: S
authors: Ahmad
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism
chemical_list: C570840:2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone; D001597:Benzylidene Compounds; D003512:Cyclohexanones; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D007371:Interferon-gamma; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3; D015232:Dinoprostone