title: Immunomodulatory and anti-inflammatory properties of artesunate in experimental colitis.
abstract: BACKGROUND
  Inflammatory bowel disease is a chronic and idiopathic gastrointestinal inflammation mediated by disregulated immune responses. Artemisinin (a chemical from a traditional Chinese herbal medicine Artemisia annua L.) and its derivatives have been proven to exhibit anti-inflammatory and immunomodulatory effects in the treatment of systemic lupus erythematosus and rheumatoid arthritis with low side-effects. This study is aimed to evaluate the potential therapeutic value of artesunate for inflammatory bowel disease.
  
  
  METHODS
  Murine colitis was induced by either oral administration of dextran sulfate sodium salt (DSS) or intrarectal delivery of 2,4,6- trinitrobenzene sulfonic acid (TNBS) or oxazolone. Mice were treated with artesunate (150mg/kg/day). Peritoneal macrophages were stimulated with lipopolysaccharide (LPS) in the presence or absence of artesunate. Changes in cytokines or proteins of interests were analyzed by enzyme-linked immunosorbent assay (ELISA) or SDS-PAGE/Western blot.
  
  
  RESULTS
  Artesunate significantly ameliorated DSS colitis and TNBS colitis (but not oxazolone colitis), including reduced weight loss and disease activity, as well as macroscopic and microscopic colonic injury. The expression of NF-κBp65 and p-IκB-α were reduced in artesunate treated TNBS colitis compared with untreated. The levels of IFN-γ, IL-17, and TNF-α were significantly decreased in artesunate treated TNBS colitis or DSS colitis. Furthermore, in vitro artesunate treatment significantly inhibited TNF-α production by LPS-activated macrophages.
  
  
  CONCLUSIONS
  Artesunate suppresses TNF-α expression in vitro and in vivo as well as T-helper (Th)1/Th17 responses in TNBS colitis model. Our data suggest a novel clinical application of artesunate as a potential therapy for Crohn's disease.
authors: Division of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China.
authors: Z
authors: Z
authors: Yang
authors: J
authors: J
authors: Ding
authors: C
authors: C
authors: Yang
authors: Y
authors: Y
authors: Gao
authors: X
authors: X
authors: Li
authors: X
authors: X
authors: Chen
authors: Y
authors: Y
authors: Peng
authors: J
authors: J
authors: Fang
authors: S
authors: S
authors: Xiao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D037621:Artemisinins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha