Planta Med 2005; 71(7): 622-627
DOI: 10.1055/s-2005-871267
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

In vivo Biodistribution of Ginkgolide B, a Constituent of Ginkgo biloba, Visualized by MicroPET

Makiko Suehiro1 , 4 , Norman R. Simpson2 , Mark D. Underwood3 , John Castrillon3 , Koji Nakanishi1 , Ronald van Heertum2
  • 1Department of Chemistry, Columbia University, New York, NY, USA
  • 2Department of Radiology, Columbia University, New York, NY, USA
  • 3Department of Psychiatry, Columbia University, New York, NY, USA
  • 4Citigroup Biomedical Imaging Center, Weill Medical College of Cornell University, New York, NY, USA
Further Information

Publication History

Received: August 24, 2004

Accepted: May 17, 2005

Publication Date:
18 July 2005 (online)

Abstract

The in vivo dynamic behavior of ginkgolide B (GB), a terpene lactone constituent of the Ginkgo biloba extracts, in the living animal was visualized by positron emission tomographic (PET) imaging using a GB analogue labeled with the positron emitter 18F. The in vivo imaging studies, combined with ex vivo dissection experiments, reveal that GB exists in 2 forms in the body: the original GB with its lactone rings closed and a second form with one of the rings open. The original GB in plasma is taken up rapidly by various organs including the liver, the intestine and possibly the stomach. Consequently, in plasma, the proportion of the ionized form of GB increases dramatically with time. Thereafter the ratio between the 2 forms appears to shift slowly towards equilibrium. The results suggest that more attention needs to be focused on in vivo dynamics between the 2 forms of GB.

References

  • 1 Curtis-Prior P, Vere D, Fray P. Therapeutic value of Gingko biloba in reducing symptoms of decline in mental function.  J Pharm Pharmacol. 1996;  51 535-41
  • 2 Le Bars P L. Magnitude of effect and special approach to Ginkgo biloba extract EGb 761 in cognitive disorders.  Pharmacopsychiatry. 2003;  36 (Suppl 1) 544-9
  • 3 Braquet P. Ginkgolides: chemistry, biology, pharmacology and clinical perspectives. J. R. Prous Science Publishers Barcelona; 1988
  • 4 Amri H, Ogwuegbu S O, Boujrad N, Drieu K, Papadopoulos V. In vitro regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginko biloba extract EGb 761 and isolated ginkgolides.  Endocrinology. 1996;  137 5707-18
  • 5 Amri H, Drieu K, Papadopoulos V. Ex vivo regulation of adrenal cortical cell steroid and protein synthesis, in response to adrenocorticotropic hormone stimulation, by Ginkgo biloba Extract Egb 761 and isolated gingkolide B.  Endocrinology. 1997;  138 5415-26
  • 6 Papadopoulos V, Widmaier E P, Amri H, Zili A, Li H, Culty M. et al . In vivo studies on the role of the peripheral benzodiazepine receptor (PBR) in steroidogenesis.  Endocrine Research. 1998;  24 479-87
  • 7 Du Z -Y, Li X -Y. Effects of ginkgolides on interleukin-1, tumor necrosis factor-α and nitric oxide production by rat microglia stimulated with lipopolysaccharides in vitro .  Arzneim-Forsch/Drug Res. 1998;  48 1126-30
  • 8 Cheng F, Siow Y L, Karmin O. Inhibition by gingkolides and bilobalide of the production of nitric oxide in macrophages (THP-1) but not in endothelial cells (HUVEC).  Biochem Biopharmacol. 2001;  61 503-10
  • 9 Kondratskaya E L, Lishko P V, Chatterjee S S, Krishtal O A. BN52021, a platelet activating factor antagonist, is a selective blocker of glycine-gated chloride channel.  Neurochemistry International. 2002;  40 647-53
  • 10 Ivic L, Sands T TJ, Fishkin N, Nakanishi K, Kriegstein AR & Strømgaard K. Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABAA receptors.  J Biol Chem. 2003;  278 49 279-85
  • 11 Suehiro M, Simpson N, van Heertum R. Radiolabeling of ginkgolide B with 18F.  J Labelled Compds Radiopharm. 2004;  47 485-91
  • 12 Suehiro M, Strømgaard K, Simpson N, Nakanishi K, van Heertum R. Radiolabeling of ginkgolide B with 18F and 3H.  J Labelled Compods Radiopharm. 2003;  46 (Suppl 1) S214
  • 13 Maruyama M, Terahara A, Itagaki Y, Nakanishi K. Ginkgolide I. Tetrahedron Lett 1967: 299-302
  • 14 Zekri O, Boudeville P, Genay P, Perly B, Braquet P, Jouenne P, Burgot J -L. Ionization constants of ginkgolide B in aqueous solution.  Anal Chem. 1996;  68 2598-604
  • 15 Fourtillan J B, Brisson A M, Girault J, Ingrand J, Decourt J P, Drieu K. et al . Proprietes pharmacocietiques du bilobalide et des ginkgolides A et B chez le sujet sain après administrations intraveineuses et orales d’extrait de Ginkgo biloba (EGb 761).  Therapie. 1995;  50 137-44
  • 16 Dalenback J, Abrahamson H, Bjornson E, Fandriks L, Mattson A, Olbe L. et al . Human duodenogastric reflux, retroperistalsis, and MMC.  Am J Physiol. 1996;  270 G113-22
  • 17 Castedal M, Bjornson E, Gretarsdottir J, Fjalling H, Abrahamson H. Scintigraphic assessment of interdigestive duodenogastric reflux in humans: distinguishing between duodenal and biliary reflux material.  Scand J Gastroenterol. 2000;  35 590-8
  • 18 Veldhuyzen van Zanten S JO, Goldie J, Hollingsworth J, Silletti C, Richardson H, Hunt R H. Secretion of intravenously administered antibiotics in gastric juice: implication for management of Helicobacter pylori .  Clin Pathol. 1992;  45 225-7
  • 19 Rathbone B J, Johnson A W, Wyatt J I, Heatley R V, Losowsky M S. Ascorbic acid: a factor concentrated in human gastric juice.  Clininal Science. 1989;  76 237-41
  • 20 Filep J, Herman F, & Braquet P. Platelet-activating factor may mediate dexamethasone-induced gastric damage in the rat.  Lipids. 1991;  26 1356-8
  • 21 Wallace J L, Steel G, Whittle B JR, Lagente V, Vargaftic B. Evidence for platelet-activating factor as a mediator of endotoxin-induced gastrointestinal damage in the rat.  Gastroenterol. 1987;  93 765-73

Makiko Suehiro, Ph. D.

Department of Radiology

Citigroup Biomedical Imaging Center

Weill Medical College of Cornell University

516 East 72nd Street

New York

NY 10021

USA

Phone: +1-212-746-5853

Email: mas2048@med.cornell.edu

    >