Tetramethylpyrazine attenuates PPAR-γ antagonist-deteriorated oxazolone-induced             colitis in mice.
Tetramethylpyrazine (TMP) is suggested to have anti-inflammatory activity. The aim of this study was to determine the role of peroxisome proliferator activated receptor γ (PPAR-γ) signaling in the pharmacologic effect of TMP on oxazolone (OXZ)-induced colitis. TMP (80 mg/kg/day i.p.) was administered daily 48 h after intrarectal instillation of OXZ, with or without PPAR-γ inhibitor [bisphenol A diglycidyl ether (BADGE) 30 mg/kg] during the 4 days before sacrifice. The inflammatory response was assessed by the disease activity index, macroscopy, histology and myeloperoxidase (MPO) activity. Expression levels of PPAR-γ, NF-κB p65, COX-2, iNOS and TNF-α mRNA in colon mucosa were determined by FQ-PCR, levels of PPAR-γ and NF-κB p65 protein were analyzed by immunohistochemistry, and the total and phosphorylated levels of p38 MAPK were assessed by western blotting. TMP significantly attenuated the damage caused by OXZ and substantially reduced the rise in MPO activity, TNF-α, iNOS, NF-κB p65 and COX-2 expression, as well as the increase in PPAR-γ production; however, no changes in the activation of p38 MAPK were observed. Inhibition of PPAR-γ signaling aggravated inflammation of colon mucosa, and increased p38 phosphrylation. TMP counteracted the effect of inhibition of PPAR-γ. We suggest that the effect of TMP treatment in ulcerative colitis may be related to PPAR-γ signaling, but is independent of PPAR-γ.
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Xiangyi
X
He
Zhong
Z
Zheng
Xiangyi
X
Yang
Yunmin
Y
Lu
Niwei
N
Chen
Weixiong
W
Chen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010081:Oxazolone; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011719:Pyrazines / Q000627:therapeutic use*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047495:PPAR gamma; D011719:Pyrazines; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; C017953:tetramethylpyrazine