期刊
ACTA PHARMACOLOGICA SINICA
卷 38, 期 1, 页码 90-99出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2016.112
关键词
type I hypersensitivity; allergic inflammation; o-vanillic acid; histamine; pro-inflammatory cytokine; high affinity IgE receptor; RBL-2H3 cells; rat peritoneal mast cells
资金
- National Research Foundation of Korea Grant - Korean Government [2014R1A5A2009242, 2012M3A9B6055416, 2016R1A2-B4008513]
- KRIBB Research Initiative Program [KGM-4611613]
- High Value-added Food Technology Development Program, Ministry of Agriculture, Food and Rural Affairs
- National Research Foundation of Korea [2012M3A9B6055416] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 mu mol/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-alpha 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-kappa B. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (Fc epsilon RI) on the surface of mast cells.
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