title: Inhibition of Th1/Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin.
abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestine which involves overproduction of pro-inflammatory cytokines and excessive functions of inflammatory cells. However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma. Therefore new therapies or drug candidates for the treatment of IBD are desperately needed. In the present study we found that icariin, a major bioactive compound from plants in Epimedium family, exerted protective effect on intestinal inflammation in mice induced by dextran sulfate sodium. Oral administration of icariin significantly attenuated the disease progression and alleviated the pathological changes of colitis. It also inhibited the production of pro-inflammatory cytokines and expression of p-p65, p-STAT1 and p-STAT3 in colon tissues. Further study showed that icariin dose-dependently inhibited the proliferation and activation of T lymphocytes, and suppressed pro-inflammatory cytokine levels of activated T cells. Moreover, icariin treatment inhibited the phosphorylations of STAT1 and STAT3 in CD4(+) T cells, which were the crucial transcription factors for Th1 and Th17 respectively. Taken together, these results indicate that icariin is a potential therapeutic agent for IBD.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Tao
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Wenjie
authors.initials: W
authors.lastname: Guo
authors.forename: Qiong
authors.initials: Q
authors.lastname: Luo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C056599:icariin