Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptide-induced toxicity in SH-SY5Y cells.
Ginkgo biloba extract EGb761 has been shown to protect against beta-amyloid peptide (Abeta)-induced neurotoxicity but the specific mechanisms remain unclear. In the present study, effects of EGb761 and two of its constituents, quercetin and ginkgolide B, on the cytotoxic action of Abeta (1-42) were tested with human neuroblastoma SH-SY5Y cells. We found that EGb761 was able to block Abeta (1-42)-induced cell apoptosis, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and activation of c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling pathways. Both quercetin and ginkgolide B may be involved in the inhibitory effects of EGb761 on JNK, ERK1/2 and Akt signaling pathways. Ginkgolide B also helped to improve mitochondrial functions but quercetin failed to show this effect. Additional experiments suggest that, protective effects of EGb761 against Abeta toxicity may be associated with its antioxidant and platelet activating factor (PAF) antagonist activities. Quercetin but not ginkgolide B is one of the constituents responsible for the antioxidant action of EGb761. Both quercetin and ginkgolide B may be involved in the PAF antagonist activity of EGb761. Overall, actions of individual EGb761 components provide further insights into direct mechanisms underlying the neuroprotective effects of EGb761.
Shi
Chun
C
Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University Guangzhou, Guangdong, China.
Zhao
Lina
L
Zhu
Bilian
B
Li
Qianxi
Q
Yew
David T
DT
Yao
Zhibin
Z
Xu
Jie
J
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D005434:Flow Cytometry; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000096983:Ginkgo Extract
D016229:Amyloid beta-Peptides; D053148:Caspase 3; D046934:Ginkgolides; D006861:Hydrogen Peroxide; D007783:Lactones; D010936:Plant Extracts; D011494:Protein Kinases; D011794:Quercetin; D017382:Reactive Oxygen Species; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C045856:ginkgolide B