Paeonol attenuates TNBS-induced colitis by inhibiting NF-kappaB and STAT1 transactivation.
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.
Ishiguro
Kazuhiro
K
Molecular Biology and Pathogenesis of Gastroenterology, School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan. kio@med.nagoya-u.ac.jp <kio@med.nagoya-u.ac.jp>
Ando
Takafumi
T
Maeda
Osamu
O
Hasegawa
Motofusa
M
Kadomatsu
Kenji
K
Ohmiya
Naoki
N
Niwa
Yasumasa
Y
Xavier
Ramnik
R
Goto
Hidemi
H
D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D019169:Jurkat Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000098:Acetophenones; D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; C013638:paeonol; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse