Ixeris dentata NAKAI Reduces Clinical Score and HIF-1 Expression in Experimental Colitis in Mice

Ixeris dentata (ID) is an herbal medicine used in Asian countries to treat indigestion, pneumonia, hepatitis, contusions, and tumors; however, its effect on intestinal inflammation is unknown. Thus, we investigated the effect of ID in the dextran sulfate sodium (DSS) model of colitis in female BALB/c mice; animals were evaluated after seven days of DSS treatment. DSS-treated mice showed considerable clinical signs, including weight loss, reduced colon length, colonic epithelial injury, infiltration of inflammatory cells in the colon tissue, and upregulation of inflammatory mediators. However, administration of ID attenuated body weight loss, colon shortening, and the increase in disease activity index score. ID also significantly decreased the colonic mucosal injury and the number of infiltrating mast cells. Moreover, ID inhibited the expressions of cyclooxygenase-2 and hypoxia-inducible factor-1α in colon tissue. Taken together, the results provide experimental evidence that ID might be a useful therapy for patients with ulcerative colitis.

[1]  G. Porro,et al.  Biologic Therapy for Inflammatory Bowel Disease , 2012, Drugs.

[2]  J. Um,et al.  The Beneficial Effect of Vanillic Acid on Ulcerative Colitis , 2010, Molecules.

[3]  E. Kuipers,et al.  Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis , 2009, Gut.

[4]  J. Yamamoto-Furusho,et al.  [IL-6 and TNF-α gene expression in the rectal mucosal of patients with chronic idiopathic ulcerative colitis and controls]. , 2009, Revista de Gastroenterología de México.

[5]  L. Roncucci,et al.  Cyclooxygenase-2 and Hypoxia-Inducible Factor-1alpha protein expression is related to inflammation, and up-regulated since the early steps of colorectal carcinogenesis. , 2009, Cancer letters.

[6]  R. Schreiber,et al.  HIF-1alpha regulates epithelial inflammation by cell autonomous NFkappaB activation and paracrine stromal remodeling. , 2008, Blood.

[7]  S. Colgan,et al.  Mucosal protection by hypoxia‐inducible factor (HIF) prolyl hydroxylase inhibition , 2008 .

[8]  J. Sung,et al.  Lactic acid bacterial fermentation increases the antiallergic effects of Ixeris dentata. , 2008, Journal of microbiology and biotechnology.

[9]  C. Taylor,et al.  Hypoxia and gastrointestinal disease , 2007, Journal of Molecular Medicine.

[10]  K. Sato,et al.  Involvement of CPI‐17 downregulation in the dysmotility of the colon from dextran sodium sulphate‐induced experimental colitis in a mouse model , 2007, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[11]  K. Takeuchi,et al.  Aggravation by Selective COX-1 and COX-2 Inhibitors of Dextran Sulfate Sodium (DSS)-Induced Colon Lesions in Rats , 2007, Digestive Diseases and Sciences.

[12]  B. Kwon,et al.  Cytotoxic and ACAT-inhibitory sesquiterpene lactones from the root ofIxeris dentata formaalbiflora , 2006, Archives of pharmacal research.

[13]  A. Munakata,et al.  Macrophage migration inhibitory factor has a proinflammatory activity via the p38 pathway in glucocorticoid-resistant ulcerative colitis. , 2006, Clinical immunology.

[14]  A. Bousvaros,et al.  Current Therapy of Inflammatory Bowel Disease in Children , 2006, Paediatric drugs.

[15]  A. El-Medany,et al.  The effects of selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimental colitis induced by acetic acid in rats. , 2005, European journal of pharmacology.

[16]  H. Cooper,et al.  Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin , 1993, Digestive Diseases and Sciences.

[17]  J. Simons,et al.  NS398 reduces hypoxia‐inducible factor (HIF)‐1α and HIF‐1 activity: Multiple‐level effects involving cyclooxygenase‐2 dependent and independent mechanisms , 2004, International journal of cancer.

[18]  John E Tomaszewski,et al.  Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. , 2004, The Journal of clinical investigation.

[19]  T. Okanoue,et al.  Reduced intestinal inflammation induced by dextran sodium sulfate in interleukin-6-deficient mice. , 2004, International journal of molecular medicine.

[20]  B. Hinz,et al.  Selective cyclooxygenase‐2 inhibitors: similarities and differences , 2004, Scandinavian journal of rheumatology.

[21]  B. Agarwal,et al.  Cox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells , 2003, Apoptosis.

[22]  Alberto Aranda,et al.  Alteraciones estructurales de las miocardiopatías , 2004 .

[23]  L. Neckers,et al.  IL‐1β mediated up‐regulation of HIF‐lα via an NFkB/COX‐2 pathway identifies HIF‐1 as a critical link between inflammation and oncogenesis , 2003 .

[24]  A. Harris,et al.  Hypoxia-inducible factors 1alpha and 2alpha are related to vascular endothelial growth factor expression and a poorer prognosis in nodular malignant melanomas of the skin. , 2003, Melanoma research.

[25]  H. Ogata,et al.  Cytokine and anti-cytokine therapies for inflammatory bowel disease. , 2003, Current pharmaceutical design.

[26]  K. Myers,et al.  Antisense Oligonucleotide Blockade of Tumor Necrosis Factor-α in Two Murine Models of Colitis , 2003, Journal of Pharmacology and Experimental Therapeutics.

[27]  J. Haddad Science review: Redox and oxygen-sensitive transcription factors in the regulation of oxidant-mediated lung injury: role for hypoxia-inducible factor-1α , 2002, Critical care.

[28]  M. Kim,et al.  Ixeris dentata extract maintains glutathione concentrations in mouse brain tissue under oxidative stress induced by kainic acid. , 2003, Journal of medicinal food.

[29]  Yun-Jin Jung,et al.  IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[30]  J. Haddad Science review: Redox and oxygen-sensitive transcription factors in the regulation of oxidant-mediated lung injury: role for nuclear factor-κB , 2002, Critical care.

[31]  I. Morita Distinct functions of COX-1 and COX-2. , 2002, Prostaglandins & other lipid mediators.

[32]  C. Mueller Tumour necrosis factor in mouse models of chronic intestinal inflammation , 2002, Immunology.

[33]  Judy H. Cho,et al.  Clinical Aspects and Pathophysiology of Inflammatory Bowel Disease , 2002, Clinical Microbiology Reviews.

[34]  Seung-Heon Hong,et al.  Ixeris dentata green sap inhibits both compound 48/80-induced aanaphylaxis-like response and IgE-mediated anaphylactic response in murine model. , 2002, Biological & pharmaceutical bulletin.

[35]  J. Hunter,et al.  Neuronal COX-2 expression in human myenteric plexus in active inflammatory bowel disease , 2001, Gut.

[36]  M. Bronner,et al.  The role of cyclooxygenase 2 in ulcerative colitis-associated neoplasia. , 2000, The American journal of pathology.

[37]  S. Targan,et al.  Role of cytokines in the pathogenesis of inflammatory bowel disease. , 2000, Annual review of medicine.

[38]  R. Blumberg,et al.  Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. , 1999, Current opinion in immunology.

[39]  Sasaki,et al.  Inhibition of dextran sulphate sodium (DSS)‐induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule‐1 (ELAM‐1) or intercellular adhesion molecule‐1 (ICAM‐1)) , 1999, Clinical and experimental immunology.

[40]  Fairclough,et al.  Selective COX‐2 inhibitors and human inflammatory bowel disease , 1999, Alimentary pharmacology & therapeutics.

[41]  W. Falk,et al.  Interferon‐gamma (IFN‐γ)‐ and tumour necrosis factor (TNF)‐induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)‐induced colitis in mice , 1999, Clinical and experimental immunology.

[42]  浜本 順博 Inhibition of dextran sulphate sodium (DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1)) , 1999 .

[43]  J. Rask-Madsen,et al.  Effects of mesalazine on the formation of lipoxygenase and cyclooxygenase products. , 1995, Advances in experimental medicine and biology.

[44]  T. Ohkusa,et al.  A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. , 1990, Gastroenterology.