title: Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia.
abstract: The neuroprotective effect of Ginkgo biloba extract (EGb 761) against ischemic injury has been demonstrated in animal models. In this study, we compared the protective effect of bilobalide, a purified terpene lactone from EGb 761, and EGb 761 against 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 forebrain 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 addition, both bilobalide and EGb 761 protected against ischemia-induced reductions in COX III mRNA in CA1 neurons prior to their death, at 1 day of reperfusion. These results suggest that oral administration of bilobalide and EGb 761 protect against ischemia-induced neuron death and reductions in mitochondrial gene expression.
authors.affiliation: Department of Anesthesiology, University of Maryland School of Medicine, MSTF 5-34, 685 West Baltimore St., Baltimore, MD 21201, USA. kchandra@anesthlab.umm.edu
authors.forename: K
authors.initials: K
authors.lastname: Chandrasekaran
authors.forename: Z
authors.initials: Z
authors.lastname: Mehrabian
authors.forename: B
authors.initials: B
authors.lastname: Spinnewyn
authors.forename: K
authors.initials: K
authors.lastname: Drieu
authors.forename: G
authors.initials: G
authors.lastname: Fiskum
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D003517:Cyclopentanes / Q000494:pharmacology*; D030401:Cytochrome-c Oxidase Deficiency / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005663:Furans / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D005849:Gerbillinae; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000096983:Ginkgo Extract
chemical_list: D003517:Cyclopentanes; D004272:DNA, Mitochondrial; D004224:Diterpenes; D003576:Electron Transport Complex IV; D005663:Furans; D046934:Ginkgolides; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012333:RNA, Messenger; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C073710:bilobalide