Paeonol attenuates TNBS-induced colitis by inhibiting NF-κB and STAT1 transactivation

被引:73
作者
Ishiguro, Kazuhiro
Ando, Takafumi
Maeda, Osamu
Hasegawa, Motofusa
Kadomatsu, Kenji
Ohmiya, Naoki
Niwa, Yasumasa
Xavier, Ramnik
Goto, Hidemi
机构
[1] Nagoya Univ, Sch Med, Showa Ku, Nagoya, Aichi 4468550, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Gastroenterol, Nagoya, Aichi 4468550, Japan
[3] Nagoya Univ, Grad Sch Med, Dept Biochem, Nagoya, Aichi 4468550, Japan
[4] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA
关键词
colitis; medical plants; TNF alpha; IFN type II; NF-kappa B; STAT1 transcription factor;
D O I
10.1016/j.taap.2006.07.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 (TNF alpha) and/or interferon gamma (IFN gamma), 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 NOS protein and mRNA expression induced by costimulation of TNF alpha and IFN gamma. Furthermore, Paeonol reduced TNF alpha-induced NF-kappa B transactivation and IFN-gamma-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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:35 / 42
页数:8
相关论文
共 26 条
[1]   The immunological and genetic basis of inflammatory bowel disease [J].
Bouma, G ;
Strober, W .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (07) :521-533
[2]   Regulation of DNA binding by Rel/NF-κB transcription factors:: structural views [J].
Chen, FE ;
Ghosh, G .
ONCOGENE, 1999, 18 (49) :6845-6852
[3]   Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia [J].
Chou, TC .
BRITISH JOURNAL OF PHARMACOLOGY, 2003, 139 (06) :1146-1152
[4]   JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].
DARNELL, JE ;
KERR, IM ;
STARK, GR .
SCIENCE, 1994, 264 (5164) :1415-1421
[5]   NF-κB signaling:: Many roads lead to Madrid [J].
Dixit, V ;
Mak, TW .
CELL, 2002, 111 (05) :615-619
[6]   Treatment of murine Th1-and Th2-mediated inflammatory bowel disease with NF-κB decoy oligonucleotides [J].
Fichtner-Feigl, S ;
Fuss, IJ ;
Preiss, JC ;
Strober, W ;
Kitani, A .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (11) :3057-3071
[7]  
Hanauer Stephen B, 2004, Rev Gastroenterol Disord, V4 Suppl 3, pS18
[8]  
Hibi T, 2003, J GASTROENTEROL, V38, P36
[9]   STUDIES ON THE MECHANISM OF ANTIAGGREGATORY EFFECT OF MOUTAN CORTEX [J].
HIRAI, A ;
TERANO, T ;
HAMAZAKI, T ;
SAJIKI, J ;
SAITO, H ;
TAHARA, K ;
TAMURA, Y ;
KUMAGAI, A .
THROMBOSIS RESEARCH, 1983, 31 (01) :29-40
[10]   Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis [J].
Jo, D ;
Liu, DY ;
Yao, S ;
Collins, RD ;
Hawiger, J .
NATURE MEDICINE, 2005, 11 (08) :892-898