Toxicology and applied pharmacology · 2006
Paeonol attenuates TNBS-induced colitis by inhibiting NF-kappaB and STAT1 transactivation.
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Ishiguro Kazuhiro, Ando Takafumi, Maeda Osamu, Hasegawa Motofusa, Kadomatsu Kenji, Ohmiya Naoki, Niwa Yasumasa, Xavier Ramnik, Goto Hidemi
Аннотация
Paeonol, a major phenolic component of Moutan Cortex, is known to have anti-inflammatory activity. However, the effect of Paeonol on colitis has not been evaluated and the molecular mechanism of its anti-inflammatory action remains unknown. The aim of this study was to determine if Paeonol enema attenuates trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. We also investigated the effects of Paeonol in colon cancer-derived CW-2 cells and T cell leukemia-derived Jurkat cells treated with tumor necrosis factor alpha (TNFalpha) and/or interferon gamma (IFNgamma), which play critical roles in TNBS-induced colitis. Paeonol enema attenuated TNBS-induced colitis judging by body weigh reduction, colon length and histological score. Myeloperoxidase activity and inducible nitric oxide synthase (iNOS) production in the colon were also reduced with Paeonol enema. In CW-2 cells, Paeonol inhibited iNOS protein and mRNA expression induced by costimulation of TNFalpha and IFNgamma. Furthermore, Paeonol reduced TNFalpha-induced NF-kappaB transactivation and IFNgamma-induced STAT1 transactivation in CW-2 cells and also in Jurkat cells. These findings suggest that Paeonol enema may be useful for the treatment of colitis.
Предметные рубрики MeSH
AcetophenonesAnimalsAnti-Inflammatory AgentsColitisColonDose-Response Relationship, DrugFemaleGene Expression Regulation, EnzymologicHumansInterferon-gammaJurkat CellsMiceMice, Inbred BALB CNF-kappa BNitric Oxide Synthase Type IIPromoter Regions, GeneticRNA, MessengerSTAT1 Transcription FactorTranscriptional ActivationTrinitrobenzenesulfonic AcidTumor Necrosis Factor-alpha