Download PDF
Planta Med 2009; 75(14): 1494-1498
DOI: 10.1055/s-0029-1185798
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Suppression of the Antigen-Stimulated RBL-2H3 Mast Cell Activation by Artekeiskeanol A

JangJa Hong1 , Hirokazu Sasaki2 , Noriyasu Hirasawa2 , Kenji Ishihara2 , Jong Hwan Kwak3 , OkPyo Zee3 , Francis J. Schmitz4 , Toshio Seyama1 , Kazuo Ohuchi1
  • 1Laboratory of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, Hiroshima, Japan
  • 2Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan
  • 3Laboratory of Pharmacognosy, Graduate School of Pharmacy, Sungkyunkwan University, Suwon, Korea
  • 4Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
Further Information

Publication History

received February 15, 2009 revised May 1, 2009

accepted May 6, 2009

Publication Date:
01 July 2009 (online)

    Permissions and Reprints

Abstract

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 µM inhibited the antigen-induced degranulation in a concentration-dependent manner, the IC50 value being 38.0 ± 0.2 µM. Degranulation induced by thapsigargin or A23187 also was inhibited by artekeiskeanol A at 10 to 100 µM. The antigen-induced increase in the levels of mRNA for tumor necrosis factor (TNF)-α 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.

Key words

Artemisia keiskeana Miq. - Compositae - artekeiskeanol A - RBL‐2H3 cells - degranulation - TNF‐α - IL‐13

References

  • 1 Shanghai Scientific and Technologic Publisher and Shougakukan .The dictionary of Chinese drugs, Vol. 1. Tokyo; Shougakukan 1985: 19
    Google Scholar
  • 2 Kwak J H, Lee K B, Schmitz F J. Four new coumarin derivatives from Artemisia keiskeana.  J Nat Prod Med. 2001;  64 1081-1083
    CrossrefPubMedGoogle Scholar
  • 3 Williams C M, Galli S J. The diverse potential effector and immunoregulatory roles of mast cells in allergic disease.  J Allergy Clin Immunol. 2000;  105 847-859
    CrossrefPubMedGoogle Scholar
  • 4 Hirasawa N, Santini F, Beaven M A. Activation of the mitogen-activated protein kinase/cytosolic phospholipase A2 pathway in a rat mast cell line. Indication of different pathways for release of arachidonic acid and secretory granules.  J Immunol. 1995;  154 5395-5401
    PubMedGoogle Scholar
  • 5 Hirasawa N, Sato Y, Fujita Y, Ohuchi K. Involvement of a phosphatidylinositol 3-kinase-p38 mitogen activated protein kinase pathway in antigen-induced IL‐4 production in mast cells.  Biochim Biophys Acta. 2000;  1456 45-55
    PubMedGoogle Scholar
  • 6 Hirasawa N, Izumi S, Linwong W, Ohuchi K. Inhibition by dexamethasone of interleukin 13 production via glucocorticoid receptor-mediated inhibition of c-Jun phosphorylation.  FEBS Lett. 2003;  554 489-493
    CrossrefPubMedGoogle Scholar
  • 7 Bridges A J, Malone D G, Jicinsky J, Chen M, Ory P, Engber W, Graziano F M. Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy.  Arthritis Rheum. 1991;  34 1116-1124
    CrossrefPubMedGoogle Scholar
  • 8 Kobayashi Y, Okunishi H. Mast cells as a target of rheumatoid arthritis treatment.  Jpn J Pharmacol. 2002;  90 7-11
    CrossrefPubMedGoogle Scholar
  • 9 Lee D M, Friend D S, Gurish M F, Benoist C, Mathis D, Brenner M B. Mast cells: a cellular link between autoantibodies and inflammatory arthritis.  Science. 2002;  297 1689-1692
    CrossrefPubMedGoogle Scholar
  • 10 Eklund K K. Mast cells in the pathogenesis of rheumatic diseases and as potential targets for anti-rheumatic therapy.  Immunol Rev. 2007;  217 38-52
    CrossrefPubMedGoogle Scholar
  • 11 Hirasawa N, Sato Y, Fujita Y, Mue S, Ohuchi K. Inhibition by dexamethasone of mitogen-induced c-Jun N-terminal kinase activation in rat basophilic leukemia cells.  J Immunol. 1998;  161 4939-4943
    PubMedGoogle Scholar
  • 12 Huber M, Hughes M R, Krystal G. Thapsigargin-induced degranulation of mast cells is dependent on transient activation of phosphatidylinositol-3 kinase.  J Immunol. 2000;  165 124-133
    PubMedGoogle Scholar
  • 13 Zhang G, Baumgartner R A, Yamada K, Beaven M A. Mitogen-activated protein (MAP) kinase regulates production of tumor necrosis factor-α and release of arachidonic acid in mast cells. Indications of communication between p 38 and p 42 MAP kinases.  J Biol Chem. 1997;  272 13397-13402
    CrossrefPubMedGoogle Scholar
  • 14 Beutler B, Cerami A. The biology of cachectin/TNF-α – a primary mediator of the host response.  Annu Rev Immunol. 1989;  7 625-655
    PubMedGoogle Scholar
  • 15 Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben T Y, Karp C L, Donaldson D D. Interleukin-13: central mediator of allergic asthma.  Science. 1998;  282 2258-2261
    CrossrefPubMedGoogle Scholar
  • 16 Gon Y, Nunomura S, Ra C. Common and distinct signalling cascades in the production of tumour necrosis factor-alpha and interleukin-13 induced by lipopolysaccharide in RBL‐2H3 cells.  Clin Exp Allergy. 2005;  35 635-642
    CrossrefPubMedGoogle Scholar
  • 17 Ryu S Y, Kou N Y, Choi H S, Ryu H, Kim T S, Kim K M. Cnidicin, a coumarin, from the root of Angelica koreana, inhibits the degranulation of mast cell and the NO generation in RAW 264.7 cells.  Planta Med. 2001;  67 172-174
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Kishiro S, Nunomura S, Nagai H, Akihisa T, Ra C. Selinidin suppresses IgE-mediated mast cell activation by inhibiting multiple steps of FcεRI signaling.  Biol Pharm Bull. 2008;  31 442-448
    CrossrefPubMedGoogle Scholar
  • 19 Watanabe J, Shinmoto H, Tsushida T. Coumarin and flavone derivatives from estragon and thyme as inhibitors of chemical mediator release from RBL‐2H3 cells.  Biosci Biotechnol Biochem. 2005;  69 1-6
    CrossrefPubMedGoogle Scholar
  • 20 Moon P D, Lee B H, Jeong H J, An H J, Park S J, Kim H R, Ko S G, Um J Y, Hong S H, Kim H M. Use of scopoletin to inhibit the production of inflammatory cytokines through inhibition of the IkappaB/NF-kappaB signal cascade in the human mast cell line HMC‐1.  Eur J Pharmacol. 2007;  555 218-225
    CrossrefPubMedGoogle Scholar
  • 21 Martin U, Roemer D. Ketotifen: a histamine release inhibitor.  Monogr Allergy. 1977;  12 145-149
    PubMedGoogle Scholar
  • 22 Fischer B, Schmutzler W. Inhibition by azelastine of the immunologically induced histamine release from isolated guinea pig mast cells.  Arzneimittelforschung. 1981;  31 1193-1195
    PubMedGoogle Scholar

Ph.D. JangJa Hong

Laboratory of Life Sciences
Faculty of Pharmacy
Yasuda Women's University

6–13–1 Yasuhigashi

Asaminami-ku

731–0153 Hiroshima

Japan

Phone: + 81 8 28 78 94 51

Fax: + 81 8 28 78 28 96

Email: hong@yasuda-u.ac.jp

      >