title: Oxymatrine prevents NF-κB nuclear translocation and ameliorates acute intestinal inflammation.
abstract: Oxymatrine is a traditional Chinese herbal product that exhibits anti-inflammatory effects in models of heart, brain and liver injury. We investigated the impact of oxymatrine in an acute model of intestinal injury and inflammation. Oxymatrine significantly decreased LPS-induced NF-κB-driven luciferase activity, correlating with diminished induction of Cxcl2, Tnfα and Il6 mRNA expression in rat IEC-6 and murine BMDC. Although oxymatrine decreased LPS-induced p65 nuclear translocation and binding to the Cxcl2 gene promoter, this effect was independent of IκBα degradation/phosphorylation. DSS-induced weight loss and histological damage were ameliorated in oxymatrine-treated C57BL/6-WT-mice. While this effect correlated with reduced colonic Il6 and Il1β mRNA accumulation, global NF-κB activity as measured in NF-κB(EGFP) mice was unaffected. Our data demonstrate that oxymatrine reduces LPS-induced NF-κB nuclear translocation and activity independently of IκBα status, prevents intestinal inflammation through blockade of inflammatory signaling and ameliorates overall intestinal inflammation in vivo.
authors.affiliation: Department of Medicine, Center for Gastrointestinal Biology & Disease, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Javier Rivera
authors.initials: JR
authors.lastname: Guzman
authors.forename: Ja Seol
authors.initials: JS
authors.lastname: Koo
authors.forename: Jason R
authors.initials: JR
authors.lastname: Goldsmith
authors.forename: Marcus
authors.initials: M
authors.lastname: Mühlbauer
authors.forename: Acharan
authors.initials: A
authors.lastname: Narula
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D051996:Transcription Factor RelA / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D016207:Cytokines; D016264:Dextran Sulfate; D004365:Drugs, Chinese Herbal; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011807:Quinolizines; D051996:Transcription Factor RelA; C037573:oxymatrine; D000093842:Matrines