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Pharmacopsychiatry 2003; 36: 89-94
DOI: 10.1055/s-2003-40447
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Neuroprotective Effects of Bilobalide, a Component of Ginkgo biloba Extract (EGb 761®) in Global Brain Ischemia and in Excitotoxicity-induced Neuronal Death

K. Chandrasekaran1 , Z. Mehrabian1 , B. Spinnewyn2 , C. Chinopoulos1 , K. Drieu2 , G. Fiskum1
  • 1Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA
  • 2IHB-IPSEN, Paris, France
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Publication History

Publication Date:
07 July 2003 (online)

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In this study, we compared the protective effect of bilobalide, a purified terpene lactone component of ginkgo biloba extract (EGb 761®), (definition see editorial) and EGb 761® against ischemic injury and against glutamate-induced excitotoxic neuronal death. In ischemic injury, we measured neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in vulnerable hippocampal regions of gerbils. At 7 days of reperfusion after 5 min of transient global ischemia, a significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons. Oral administration of EGb 761® at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA. In rat cerebellar neuronal cultures, addition of bilobalide or EGb 761® protected in a dose-dependent manner against glutamate-induced excitotoxic neuronal death (effective concentration [EC50] = 5 μg/ml (12 μM) for bilobalide and 100 μg/ml for EGb 761®). These results suggest that both EGb 761® and bilobalide are protective against ischemia-induced neuronal death in vivo and glutamate-induced neuronal death in vitro by synergistic mechanisms involving anti-excitotoxicity, inhibition of free radical generation, scavenging of reactive oxygen species, and regulation of mitochondrial gene expression.

Abbreviations

NMDA:N-methyl-D-aspartate

ROS:reactive oxygen species

mtDNA:mitochondrial DNA

Key words

Hippocampus - Histology - In situ hybridization - Mitochondrial mRNA - Cytochrome oxidase

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Krish Chandrasekaran, Ph. D.

Department of Anesthesiology

University of Maryland School of Medicine

MSTF 5-34

685 West Baltimore St

Baltimore

MD 21201

USA

Phone: 410-706-3418

Fax: 410-706-2550

Email: kchandra@anesthlab.umm.edu