Implication of phosphatidylinositol-3 kinase/Akt/glycogen synthase kinase-3β pathway in ginsenoside Rb1's attenuation of beta-amyloid-induced neurotoxicity and tau phosphorylation.
Ginseng has long been used to alleviate many ailments, particularly those associated with aging and memory deterioration. In the present study we aimed to investigate the neuroprotective effects of ginsenoside Rb1, against Aβ(1-42) toxicity in cultured cortical neurons and also the potential involvement of PI3K/Akt/GSK-3β signal pathway. Cortical neurons were pre-treated with ginsenoside Rb1 (20, 40, 100 μM) or LiCl (1, 5, 10 mM) for 24 h, and then were co-treated with 20 μM Aβ(1-42) for 12 h. In some experiments to evaluate the mechanism of Rb1 action, a PI3K inhibitor (LY294002 10 μM) was co-administered with Rb1 for the 24-h pretreatment. We revealed that Rb1 significantly attenuated Aβ(1-42)-induced neurotoxicity and tau hyperphosphorylation at multiple AD-related sites in a dose-dependent manner. Simultaneously, it increased the levels of phospho-Ser(473)-Akt and down-regulated GSK-3β activity by PI3K activation. The neuroprotective effects of Rb1 against Aβ(1-42)-induced neurotoxicity and tau hyperphosphorylation were blocked by LY294002 (10 μM), a PI3K inhibitor. In addition, Rb1 reversed the Aβ(1-42)-induced decrease in phosphorylation cyclic AMP response element binding (CREB) protein, which could also be blocked by the PI3K inhibitor. All these findings suggest that Rb1 may represent a potential treatment strategy for Alzheimer's disease.
Department of Pathology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Ruiping
R
Zhao
Zhaoxu
Z
Zhang
Yuejia
Y
Song
Desheng
D
Wang
Jiping
J
Qi
Shirong
S
Wen
D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D036145:Ginsenosides / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D036145:Ginsenosides; D018696:Neuroprotective Agents; D016875:tau Proteins; C442759:ginsenoside Rb1; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3