Dosage effects of EGb761 on hydrogen peroxide-induced cell death in SH-SY5Y cells.
Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, is one of the most popular herbal supplements, taken for its multivalent properties. In this study, dosage effects of EGb761 on hydrogen peroxide (H(2)O(2))-induced apoptosis of human neuroblastoma SH-SY5Y cells were investigated. It was found that H(2)O(2)-induced apoptotic cell death in SH-SY5Y cells, which was revealed in DNA fragmentation, mitochondrial membrane potential depolarization, and activation of Akt, c-Jun N-terminal kinases (JNK) and caspase 3. Low doses of EGb761 (50-100 microg/ml) inhibited H(2)O(2)-induced cell apoptosis via inactivation of Akt, JNK and caspase 3 while high doses of EGb761 (250-500 microg/ml) enhanced H(2)O(2) toxicities via inactivation of Akt and enhancement of activation of JNK and caspase 3. Additional experiments revealed that H(2)O(2) decreased intracellular GSH content, which was also inhibited by low concentrations of EGb761 but enhanced after high concentrations of EGb761 treatment. This further suggests to us that dosage effects of EGb761 on apoptotic signaling proteins may be correlated with regulation of cell redox state. Therefore, treatment dosage may be one of the vital factors that determine the specific action of EGb761 on oxidative stress-induced cell apoptosis. To understand the mechanisms of dosage effects of EGb761 may have important clinical implications.
Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University Guangzhou, Guangdong 510080, China.
Chun
C
Shi
Lina
L
Zhao
Bilian
B
Zhu
Qianxi
Q
Li
David T
DT
Yew
Zhibin
Z
Yao
Jie
J
Xu
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000096983:Ginkgo Extract
D053148:Caspase 3; D005978:Glutathione; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract