Anti‐allergic action of anti‐malarial drug artesunate in experimental mast cell‐mediated anaphylactic models

Chang, Cheng; Ng, David S.W.; Chan, Taizan; Guan, Sheng-Uei; Ho, Wanxing Eugene; Koh, A H M; Bian, Jin-Song; Lau, H. Y. A.; Wong, W.S. Fred

doi:10.1111/all.12077

Cited by 55 publications

(38 citation statements)

References 43 publications

(65 reference statements)

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“…The mechanism by which artesunate inhibits the PI3K/Akt/p70 S6K pathway remains to be fully elucidated. Cheng's recent findings in mast cells suggest that Syk and phospholipase C g are potential targets of artesunate that are upstream of PI3K (30). Further investigation is warranted to determine whether these two proteins upstream of PI3K are involved in human ASM cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

The Antimalarial Drug Artesunate Inhibits Primary Human Cultured Airway Smooth Muscle Cell Proliferation

Tan¹,

Ong²,

Chang³

et al. 2014

Am J Respir Cell Mol Biol

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Airway smooth muscle (ASM) cell hyperplasia contributes to airway wall remodeling (AWR) in asthma. Glucocorticoids, which are used as first-line therapy for the treatment of inflammation in asthma, have limited impact on AWR, and protracted usage of high doses of glucocorticoids is associated with an increased risk of side effects. Moreover, patients with severe asthma often show reduced sensitivity to glucocorticoids. Artesunate, a semisynthetic artemisinin derivative used to treat malaria with minimal toxicity, attenuates allergic airway inflammation in mice, but its impact on AWR is not known. We examined the effects of artesunate on ASM proliferation in vitro and in vivo. Primary human ASM cells derived from nonasthmatic donors were treated with artesunate before mitogen stimulation. Artesunate reduced mitogen-stimulated increases in cell number and cyclin D1 protein abundance but had no significant effect on ERK1/2 phosphorylation. Artesunate, but not dexamethasone, inhibited phospho-Akt and phospho-p70 S6K protein abundance. Artesunate, but not dexamethasone, inhibited mitogen-stimulated increases in cell number, cyclin D1, and phospho-Akt protein abundance on ASM cells derived from asthmatic donors. In a murine model of allergic asthma, artesunate reduced the area of a-smooth muscle actin-positive cells and decreased cyclin D1 protein abundance. Our study provides a basis for the future development of artesunate as a novel anti-AWR agent that targets ASM hyperplasia via the PI3K/Akt/p70 S6K pathway and suggests that artesunate may be used as combination therapy with glucocorticoids.

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Section: Discussionmentioning

confidence: 99%

The Antimalarial Drug Artesunate Inhibits Primary Human Cultured Airway Smooth Muscle Cell Proliferation

Tan¹,

Ong²,

Chang³

et al. 2014

Am J Respir Cell Mol Biol

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“…The IgE-mediated PCA model is also another well-characterized animal model of allergic reaction. Local injection of anti-DNP IgE followed by an intravenous antigenic challenge induces local plasma extravasation and vascular permeability [30] . In both animal models, the increase in histamine release results in vasodilation, which eventually causes hypothermia and Evans blue pigmentation.…”

Section: Discussionmentioning

confidence: 99%

2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway

Kim¹,

Kim³

et al. 2016

Acta Pharmacol Sin

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Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100 μmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells.

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“…[38][39][40][41][42] Artesunate is antagonistic with the formation of IgE and its mechanisms of action against parasites. 43,44 Worse even, a 5-fold increase in gametocytogenesis in Plasmodium falciparum has been documented for chloroquine in vitro. 45 It is shocking to read in a recent paper that while chloroquine may significantly reduce mortality, but whether it will interfere with the host immune system is currently unknown.…”

Section: 37mentioning

confidence: 99%

Antibodies, prophylaxis, transmission

Lutgen¹

2018

PPIJ

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Anti‐allergic action of anti‐malarial drug artesunate in experimental mast cell‐mediated anaphylactic models

Abstract: 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.

Cited by 55 publications

References 43 publications

The Antimalarial Drug Artesunate Inhibits Primary Human Cultured Airway Smooth Muscle Cell Proliferation

The Antimalarial Drug Artesunate Inhibits Primary Human Cultured Airway Smooth Muscle Cell Proliferation

2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway

Antibodies, prophylaxis, transmission

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