Anti-apoptotic properties of Ginkgo biloba extract EGb 761 in differentiated PC12 cells.
Standard Ginkgo biloba leaf extract (EGb 761) has been known to have neuroprotective effects ranging from molecular and cellular, to animal and human studies, however, the cellular and molecular mechanisms remain unclear. Using PC 12 cells, a well-established model for studying neuroprotection, we have determined the mechanism of action of EGb 761 on cell survival following apoptosis induced by serum-deprivation or treatment with staurosporine (STS). Our results show that EGb 761 treatments of PC12 cells are able to prevent serum deprivation- and STS-induced mitochondrial damage, attenuate release of cytochrome c and DNA fragmentation. EGb 761, but not vitamin E. inhibited STS-induced activation of the caspase-3 enzyme. Two of the EGb 761 components, bilobalide B and ginkgolide C show more significant inhibition than the EGb 761 extract. Furthermore, DNA microarray assay results indicate that transcription of multiple apoptosis-related genes is either up- or down-regulated in cells treated with EGb 761. These results suggest that inhibition of apoptotic machinery may, at least in part, mediate multiple neuroprotective effects of EGb 761, and that EGb 761 and vitamin E act on different molecular paths to provide neuroprotection.
Smith
Julie V
JV
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg 39406-5018, USA.
Burdick
Adam J
AJ
Golik
Pawel
P
Khan
Ikhlas
I
Wallace
Douglas
D
Luo
Yuan
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D003574:Cytochrome c Group / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020441:Ginkgo biloba; D008928:Mitochondria / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D000096983:Ginkgo Extract
D000975:Antioxidants; D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010936:Plant Extracts; D019311:Staurosporine; D014810:Vitamin E; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C506444:CASP12 protein, human; C505407:CASP3 protein, human; C506443:Casp12 protein, rat; C505410:Casp3 protein, rat