Anti-allergic action of anti-malarial drug artesunate in experimental mast cell-mediated anaphylactic models
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AbstractBackground 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 PLC?1 phosphorylation, production of IP3, 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.
All Author(s) ListCheng C, Ng DSW, Chan TK, Guan SP, Ho WE, Koh AHM, Bian JS, Lau HYA, Wong WSF
Journal nameAllergy
Detailed descriptionTo ORKTS: doi: 10.1111/all.12077
Volume Number68
Issue Number2
Pages195 - 203
LanguagesEnglish-United Kingdom
Keywordsanaphylactic contraction; Ca2+imaging; passive cutaneous anaphylaxis; passive systemic anaphylaxis; phospholipase C?1; Syk kinase
Web of Science Subject CategoriesAllergy; ALLERGY; Immunology; IMMUNOLOGY

Last updated on 2021-11-05 at 00:32