Macelignan inhibits histamine release and inflammatory mediator production in activated rat basophilic leukemia mast cells.
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.
Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
Young Sun
YS
Han
Myung-Suk
MS
Kim
Jae-Kwan
JK
Hwang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D000001:Calcimycin; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D006967:Hypersensitivity / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism*; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D026323:Myristica; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D018793:Interleukin-13; D017705:Lignans; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D017997:Leukotriene C4; D000001:Calcimycin; C502026:macelignan; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D001619:beta-N-Acetylhexosaminidases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium