Hibifolin, a flavonol glycoside, prevents beta-amyloid-induced neurotoxicity in cultured cortical neurons.
The toxicity of aggregated beta-amyloid (A beta) has been implicated as a critical cause in the development of Alzheimer's disease (AD). Hibifolin, a flavonol glycoside derived from herbal plants, possessed a strong protective activity against cell death induced by aggregated A beta. Application of hibifolin in primary cortical neurons prevented the A beta-induced cell death in a dose-dependent manner. In cultured cortical neurons, the pre-treatment of hibifolin abolished A beta-induced Ca(2+) mobilization, and also reduced A beta-induced caspase-3 and caspase-7 activation. Moreover, DNA fragmentation induced by A beta could be suppressed by hibifolin. In addition to such protection mechanisms, hibifolin was able to induce Akt phosphorylation in cortical neurons, which could be another explanation for the neuroprotection activity. These results therefore provided the first evidence that hibifolin protected neurons against A beta-induced apoptosis and stimulated Akt activation, which would be useful in developing potential drugs or food supplements for treating AD.
Zhu
Judy T T
JT
Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Kowloon, Hong Kong SAR, China.
Choi
Roy C Y
RC
Xie
Heidi Q
HQ
Zheng
Ken Y Z
KY
Guo
Ava J Y
AJ
Bi
Cathy W C
CW
Lau
David T W
DT
Li
Jun
J
Dong
Tina T X
TT
Lau
Brad W C
BW
Chen
Ji J
JJ
Tsim
Karl W K
KW
D016229:Amyloid beta-Peptides / Q000502:physiology* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005419:Flavonoids / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000502:physiology* / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051381:Rats; D015398:Signal Transduction
D016229:Amyloid beta-Peptides; D005419:Flavonoids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C087346:hibifolin; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium