title: Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via PI3K/Akt Signaling Pathway.
abstract: The neurotoxicity of amyloid- β (A β ) has been implicated as a critical cause of Alzheimer's disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated from Uncaria rhynchophylla, exerts neuroprotective effect against Aβ 25-35-induced neurotoxicity in vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN against Aβ 25-35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation in Aβ 25-35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3 β (p-GSK-3 β ). Lithium chloride blocked Aβ 25-35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3 β inhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversed Aβ 25-35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN against Aβ 25-35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3 β signaling pathway.
authors: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors: Yan-Fang
authors: YF
authors: Xian
authors: Zhi-Xiu
authors: ZX
authors: Lin
authors: Qing-Qiu
authors: QQ
authors: Mao
authors: Jian-Nan
authors: JN
authors: Chen
authors: Zi-Ren
authors: ZR
authors: Su
authors: Xiao-Ping
authors: XP
authors: Lai
authors: Paul Siu-Po
authors: PS
authors: Ip