Planta Med 2001; 67(9): 807-810
DOI: 10.1055/s-2001-18842
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Antithrombotic Effect of Geniposide and Genipin in the Mouse Thrombosis Model

Yasuhiro Suzuki, Kazunao Kondo, Yasuhiko Ikeda, Kazuo Umemura
  • Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Further Information

Publication History

January 8, 2001

March 4, 2001

Publication Date:
06 December 2001 (online)

Abstract

Geniposide is one of the constituents of Gardenia fruit (Gardenia jasminoides Ellis, Rubiaceae), which has been used in traditional medicine. Although its anti-inflammatory and antithrombotic effects have been reported, the way it acts is still unclear. We have investigated the effects of geniposide and its metabolite genipin on thrombogenesis and platelet aggregation. In an in vivo model, geniposide and genipin significantly (P < 0.05) prolonged the time required for thrombotic occlusion induced by photochemical reaction in the mouse femoral artery. In an in vitro study, both geniposide and genipin inhibited collagen-induced, but did not inhibit arachidonate-induced, mouse platelet aggregation. However aspirin, a cyclooxygenase inhibitor, inhibited arachidonate-induced platelet aggregation but only partially inhibited the collagen-induced one. We also showed, by measuring PLA2-catalyzed arachidonic acid release, that geniposide inhibited phospholipase A2 (PLA2) activity. We conclude that geniposide showed an antithrombotic effect in vivo due to the suppression of platelet aggregation. PLA2 inhibition by geniposide is one possible anti-platelet mechanism.

References

  • 1 Ross R. The pathogenesis of atherosclerosis - an update.  New England Journal of Medicine. 1986;  314 488-500
  • 2 Fuster V, Badimon L, Cohen M, Ambrose J A, Badimon J J, Chesebro J. Insights into the pathogenesis of acute ischemic syndromes.  Circulation. 1988;  77 1213-20
  • 3 Willerson J T, Golino P, Eidt J, Campbell W B, Buja L M. Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications.  Circulation. 1989;  80 198-205
  • 4 Sakuragawa N, Yuasa K, Niwa M, Kondo S. Studies on Wakan-yakus.  Acta Medica et Biologica. 1984;  32 107-13
  • 5 Akao T, Kobayashi K, Aburada M. Enzymic studies on the animal and intestinal bacterial metabolism of geniposide.  Biol. Pharm. Bull.. 1994;  17 1573-6
  • 6 Tanaka M, Kigawa M, Mitsuhashi H, Wakamatsu T. The practical method for the preparation of iridoid aglycons from their glycosides.  Heterocycles. 1991;  32 1451-4
  • 7 Shimazawa M, Takiguchi Y, Umemura K, Kondo K, Nakashima M. Antithrombotic effects in a rat model of aspirin-insensitive arterial thrombosis of desethyl KBT-3022, the main active metabolite of a new antiplatelet agent, KBT-3022.  European Journal of Pharmacology. 1997;  328 183-9
  • 8 Kikuchi S, Umemura K, Kondo K, Saniabadi A R, Nakashima M. Photochemically induced endothelial injury in the mouse as a screening model for inhibitors of vascular intimal thickening.  Arteriosclerosis, Thrombosis & Vascular Biology. 1998;  18 1069-78
  • 9 Akagi K, Nagao T, Urushidani T. Calcium oscillations in single cultured Chinese hamster ovary cells stably transfected with a cloned human cholecystokinin (CCK)B receptor.  Japanese Journal of Pharmacology. 1997;  75 33-47
  • 10 Martinez-Salgado C, Rodriguez-Barbero A, Rodriguez-Puyol D, Perez de Lema G, Lopez-Novoa J M. Involvement of phospholipase A2 in gentamicin-induced rat mesangial cell activation.  American Journal of Physiology. 1997;  273 F60-6
  • 11 Hirata Y, Takiguchi Y, Wada K, Matsuno H, Umemura K, Uematsu T et al. Roles of platelet-activating factor, thromboxane A2, ADP and thrombin in thrombogenesis in the guinea pig.  European Journal of Pharmacology. 1993;  231 421-5
  • 12 Mellwig K P, Jakobs K H. Inhibition of platelet adenylate cyclase by ADP.  Thrombosis Research. 1980;  18 7-17
  • 13 Rink T J, Sage S O. Calcium signaling in human platelets.  Annual Review of Physiology. 1990;  52 431-49
  • 14 Rand M L, Perry D W, Packham M A, Gemmell C H, Yeo E L, Kinlough-Rathbone R L. Conditions influencing release of granule contents from human platelets in citrated plasma induced by ADP or the thrombin receptor activating peptide SFLLRN: direct measurement of percent release of beta-thromboglobulin and assessment by flow cytometry of P-selectin expression.  American Journal of Hematology. 1996;  52 288-94
  • 15 Packham M A, Bryant N L, Guccione M A, Kinlough-Rathbone R L, Mustard J F. Effect of the concentration of Ca2+ in the suspending medium on the responses of human and rabbit platelets to aggregating agents.  Thrombosis & Haemostasis. 1989;  62 968-76
  • 16 Jantzen H M, Gousset L, Bhaskar V, Vincent D, Tai A, Reynolds E E, Conley P B. Evidence for two distinct G-protein-coupled ADP receptors mediating platelet activation.  Thrombosis & Haemostasis. 1999;  81 111-7

Y. Suzuki

Department of Pharmacology

Hamamatsu University School of Medicine

1-20-1 Handayama

Hamamatsu, 431-3192

Japan

Email: yapplel@hama-med.ac.jp

Fax: +81-53-435 2270

Phone: Tel.: +81-53-435 2271