Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25-35 partly via up-regulation of brain-derived neurotrophic factor.
Alzheimer's disease is a complex genetic disease in the global prevalence of up to 15 million people. The accumulation of beta-amyloid peptides leads to the subsequent disruption of neuronal process, abnormal phosphorylation of tau and ultimately the dysfunction and death of neurons. Ginkgolide B is a well-defined plant extract which is safe in nature, effective, economic and has minor side effects. This study aims at investigating the neuroprotective effects of Ginkgolide B against Aβ25-35-induced apoptosis in cultured hippocampal neurons, and further exploring the possible mechanisms concerned. We first conducted the study of the Aβ25-35-induced apoptosis characterized by the changes in cell viability, morphology, extracellular K(+) concentration, lactate dehydrogenase level, and the caspase-3 activity in hippocampal neurons. Moreover, the expression of brain-derived neurotrophic factor mRNA and the protein synthesis in neurons were detected via RT-PCR and Western-blot assay. It was found out that Aβ25-35-induced apoptosis was attenuated by Ginkgolide B. Ginkgolide B caused brain-derived neurotrophic factor up-regulation when cells were subjected to Aβ25-35 insults. The above results indicate that Ginkgolide B may significantly dampen Aβ25-35-induced apoptosis, and the neuroprotective effects may be intimately associated with brain-derived neurotrophic factor up-regulation caused by Ginkgolide B. These findings may demonstrate the neuroprotective effects of Ginkgolide B and offer new evidences to the possible mechanisms.
Xiao
Qian
Q
Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China.
Wang
Chao
C
Li
Junchang
J
Hou
Qian
Q
Li
Jinghua
J
Ma
Jing
J
Wang
Wen
W
Wang
Zongren
Z
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005343:Fibrinolytic Agents / Q000378:metabolism / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000494:pharmacology; D046934:Ginkgolides / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D005343:Fibrinolytic Agents; D005456:Fluorescent Dyes; D046934:Ginkgolides; D007783:Lactones; D009414:Nerve Growth Factors; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C045856:ginkgolide B; D053148:Caspase 3