Bilobalide, a component of the Ginkgo biloba extract (EGb 761), protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity

Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):663-9.

Abstract

In this study, the effect of bilobalide, a purified terpene lactone component of the Ginkgo biloba extract (EGb 761), and EGb 761 against ischemic injury and against glutamate-induced excitotoxic neuronal death was compared. In the case of ischemic injury, neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in the hippocampal regions of gerbils was measured. A significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons at 7-days of reperfusion after 5 min of transient global forebrain ischemia. 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 hippocampal CA1 neurons against ischemia-induced neuronal death and 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 microg/ml (12 microM) forbilobalide and 100 microg/ml for EGb 761]. These results suggest thatboth EGb 761 and bilobalide protect 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Brain Ischemia / drug therapy
  • Cell Death / drug effects
  • Cerebellum / drug effects
  • Cyclopentanes / administration & dosage
  • Cyclopentanes / pharmacology*
  • Diterpenes*
  • Electron Transport Complex IV / biosynthesis
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Furans / administration & dosage
  • Furans / pharmacology*
  • Gerbillinae
  • Ginkgo biloba
  • Ginkgolides
  • Glutamic Acid / toxicity
  • Hippocampus / drug effects
  • Male
  • Neurons / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Plant Extracts / pharmacology
  • Reperfusion Injury / drug therapy

Substances

  • Cyclopentanes
  • Diterpenes
  • Furans
  • Ginkgolides
  • Neuroprotective Agents
  • Plant Extracts
  • Ginkgo biloba extract
  • Glutamic Acid
  • Electron Transport Complex IV
  • bilobalide