Suppression of the antigen-stimulated RBL-2H3 mast cell activation by Artekeiskeanol A.
Effects of artekeiskeanol A, a newly isolated coumarin derivative from Artemisa keiskeana Miq. (Compositae), the extract of which is used for treatment of rheumatoid arthritis as a folk medicine, on the antigen-induced activation of RBL-2H3 cells were examined. RBL-2H3 cells were sensitized with dinitrophenol (DNP)-specific IgE, and then stimulated with the antigen DNP-conjugated human serum albumin (DNP-HSA). Artekeiskeanol A at 10 to 100 microM inhibited the antigen-induced degranulation in a concentration-dependent manner, the IC(50) value being 38.0 + or - 0.2 microM. Degranulation induced by thapsigargin or A23187 also was inhibited by artekeiskeanol A at 10 to 100 microM. The antigen-induced increase in the levels of mRNA for tumor necrosis factor (TNF)-alpha and interleukin (IL)-13 and phosphorylations of Akt, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p44/42 MAPK were also suppressed by artekeiskeanol A. Our findings suggested that the effectiveness of the extract of A. keiskeana might partly be due to the inhibition of mast cell activation by artekeiskeanol A.
Hong
JangJa
J
Laboratory of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, Hiroshima, Japan.
Sasaki
Hirokazu
H
Hirasawa
Noriyasu
N
Ishihara
Kenji
K
Kwak
Jong Hwan
JH
Zee
OkPyo
O
Schmitz
Francis J
FJ
Seyama
Toshio
T
Ohuchi
Kazuo
K
D000818:Animals; D000941:Antigens / Q000378:metabolism; D019306:Artemisia / Q000737:chemistry*; D000001:Calcimycin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E; D007155:Immunologic Factors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012709:Serum Albumin; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000941:Antigens; D003374:Coumarins; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D018793:Interleukin-13; D010936:Plant Extracts; D012333:RNA, Messenger; D012709:Serum Albumin; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha; C108955:artekeiskeanin A; D007073:Immunoglobulin E; D000001:Calcimycin; D019284:Thapsigargin; D020928:Mitogen-Activated Protein Kinases