title: Inhibition of lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression by 4-[(2'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate from Moringa oleifera.
abstract: Moringa oleifera Lamarck is commonly consumed for nutritional or medicinal properties. We recently reported the isolation and structure elucidation of novel bioactive phenolic glycosides, including 4-[(2'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate (RBITC), which was found to suppress inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 mouse macrophage cells. Inhibitors of proteins such as cyclooxygenase-2 (COX-2) and iNOS are potential antiinflammatory and cancer chemopreventive agents. The inhibitory activity of RBITC on NO production (IC(50) = 0.96 ± 0.23 μM) was greater than that mediated by other well-known isothiocyanates such as sulforaphane (IC(50) = 2.86 ± 0.39 μM) and benzyl isothiocyanate (IC(50) = 2.08 ± 0.28 μM). RBITC inhibited expression of COX-2 and iNOS at both the protein and mRNA levels. Major upstream signaling pathways involved mitogen-activated protein kinases and nuclear factor-κB (NF-κB). RBITC inhibited phosphorylation of extracellular signal-regulated kinase and stress-activated protein kinase, as well as ubiquitin-dependent degradation of inhibitor κBα (IκBα). In accordance with IκBα degradation, nuclear accumulation of NF-κB and subsequent binding to NF-κB cis-acting element was attenuated by treatment with RBITC. These data suggest RBITC should be included in the dietary armamentarium of isothiocyanates potentially capable of mediating antiinflammatory or cancer chemopreventive activity.
authors.affiliation: College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii 96720, USA.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Sarot
authors.initials: S
authors.lastname: Cheenpracha
authors.forename: Leng Chee
authors.initials: LC
authors.lastname: Chang
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases; D015971:Gene Expression Regulation, Enzymologic; D017879:Isothiocyanates / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D029588:Moringa oleifera / Q000737:chemistry*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012210:Rhamnose / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: C568824:4-((2'-O-acetylrhamnosyloxy)benzyl)isothiocyanate; D004791:Enzyme Inhibitors; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C037152:isothiocyanic acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D012210:Rhamnose