title: Anti-allergic action of anti-malarial drug artesunate in experimental mast cell-mediated anaphylactic models.
abstract: BACKGROUND
  Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis.
  
  
  METHODS
  Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated.
  
  
  RESULTS
  Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2)  level in mast cells.
  
  
  CONCLUSIONS
  We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore City, Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: D S W
authors.initials: DS
authors.lastname: Ng
authors.forename: T K
authors.initials: TK
authors.lastname: Chan
authors.forename: S P
authors.initials: SP
authors.lastname: Guan
authors.forename: W E
authors.initials: WE
authors.lastname: Ho
authors.forename: A H M
authors.initials: AH
authors.lastname: Koh
authors.forename: J S
authors.initials: JS
authors.lastname: Bian
authors.forename: H Y A
authors.initials: HY
authors.lastname: Lau
authors.forename: W S F
authors.initials: WS
authors.lastname: Wong
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D015550:Cell Degranulation / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D051379:Mice; D011897:Random Allocation
chemical_list: D018926:Anti-Allergic Agents; D000962:Antimalarials; D037621:Artemisinins; D007073:Immunoglobulin E; D000077332:Artesunate