Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia.
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.
Chandrasekaran
K
K
Department of Anesthesiology, University of Maryland School of Medicine, MSTF 5-34, 685 West Baltimore St., Baltimore, MD 21201, USA. kchandra@anesthlab.umm.edu
Mehrabian
Z
Z
Spinnewyn
B
B
Drieu
K
K
Fiskum
G
G
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
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