Abstract
Type I allergy is characterized by the release of granule-associated mediators, lipid-derived substances, cytokines, and chemokines by activated mast cells. To evaluate the anti-allergic effects of macelignan isolated from Myristica fragrans Houtt., we determined its ability to inhibit calcium (Ca(2+)) influx, degranulation, and inflammatory mediator production in RBL-2 H3 cells stimulated with A23187 and phorbol 12-myristate 13-acetate. Macelignan inhibited Ca(2+) influx and the secretion of β-hexosaminidase, histamine, prostaglandin E(2), and leukotriene C(4); decreased mRNA levels of cyclooxygenase-2, 5-lipoxygenase, interleukin-4 (IL-4), IL-13, and tumor necrosis factor-α; and attenuated phosphorylation of Akt and the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. These results indicate the potential of macelignan as a type I allergy treatment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Arachidonate 5-Lipoxygenase / genetics
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Calcimycin
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Calcium / metabolism
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Cell Degranulation / drug effects
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Cell Line, Tumor
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Cyclooxygenase 2 / genetics
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Dinoprostone / metabolism
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Histamine Release / drug effects*
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Hypersensitivity / drug therapy*
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Inflammation Mediators / metabolism*
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Interleukin-13 / genetics
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Interleukin-4 / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism
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Leukemia, Basophilic, Acute / metabolism
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Leukotriene C4 / metabolism
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Lignans / pharmacology*
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Lignans / therapeutic use
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Mast Cells / drug effects
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Mast Cells / immunology*
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Mast Cells / metabolism*
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Myristica
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Phosphorylation / drug effects
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Plant Extracts / pharmacology
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Plant Extracts / therapeutic use
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Proto-Oncogene Proteins c-akt / metabolism
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Rats
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Tetradecanoylphorbol Acetate
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Tumor Necrosis Factor-alpha / genetics
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beta-N-Acetylhexosaminidases / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Inflammation Mediators
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Interleukin-13
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Lignans
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Plant Extracts
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Tumor Necrosis Factor-alpha
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Interleukin-4
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Leukotriene C4
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Calcimycin
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macelignan
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Arachidonate 5-Lipoxygenase
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Cyclooxygenase 2
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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beta-N-Acetylhexosaminidases
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Dinoprostone
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Tetradecanoylphorbol Acetate
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Calcium