Neuroprotective effects of puerarin against beta-amyloid-induced neurotoxicity in PC12 cells via a PI3K-dependent signaling pathway

作者:Xing Guihua; Dong Miaoxian; Li Xiaoming; Zou Yu; Fan Li; Wang Xiaoli; Cai Defu; Li Chengchong; Zhou Li; Liu Jicheng; Niu Yingcai*
来源:Brain Research Bulletin, 2011, 85(3-4): 212-218.
DOI:10.1016/j.brainresbull.2011.03.024

摘要

Epidemiological data have indicated that estrogen replacement therapy (ERT) can decrease the risk of developing Alzheimer's disease (AD). Phytoestrogens have been proposed as potential alternatives to ERT. The aim of the present study was to assess the neuroprotective effects of puerarin, a phytoestrogen isolated from Pueraria lobata, against the toxicity of beta-amyloid (A beta) in relation to the mitochondria-mediated cell death process, and to elucidate the role the activation of Akt and modulation of the pro- and antiapoptotic proteins in puerarin-induced neuroprotection. The present study shows that puerarin afforded protection against A beta-induced toxicity through inhibiting apoptosis in PC12 cells. This result was also confirmed by the activated caspase-3 assay. P-Akt, Bcl-2 and p-Bad expression increased after pretreatment with puerarin in PC12 cells exposed to A beta(25-35), whereas Bax expression and cytochrome c release decreased. Interestingly, these effects of puerarin against A beta(25-35) insult were abolished by wortmannin, an inhibitor of PI3K phosphorylation. These findings suggest that puerarin prevent A beta-induced neurotoxicity through inhibiting neuronal apoptosis, and might be a potential preventive or therapeutic agent for AD.