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Anti‐allergic action of anti‐malarial drug artesunate in experimental mast cell‐mediated anaphylactic models
Author(s) -
Cheng C.,
Ng D. S. W.,
Chan T. K.,
Guan S. P.,
Ho W. E.,
Koh A. H. M.,
Bian J. S.,
Lau H. Y. A.,
Wong W. S. F.
Publication year - 2013
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12077
Subject(s) - artesunate , degranulation , immunoglobulin e , mast cell , histamine , anaphylaxis , pharmacology , immunology , ovalbumin , allergy , medicine , immune system , receptor , antibody , plasmodium falciparum , malaria
Background Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross‐linking of allergen‐specific I g E ‐bound high‐affinity I g E receptors, leading to immediate mast cell degranulation. Artesunate is a semi‐synthetic derivative of artemisinin, an active component of the medicinal plant A rtemisia 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 I g E ‐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 ‐2 H 3 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 I g E ‐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 I g E ‐mediated degranulation of RBL ‐2 H 3 mast cells and human culture mast cells. Artesunate was found to inhibit I g E ‐induced S yk and PLC γ1 phosphorylation, production of IP 3 , and rise in cytosolic C a +2 level in mast cells. Conclusions We report here for the first time that artesunate possesses anti‐allergic activity by blocking I g E ‐induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell‐mediated allergic disorders.