The Institute of Medicine, Qiqihar Medical University, 333 BuKui Street, JianHua District, Qiqihar 161042, China.
Brain Res Bull. 2011 May 30;85(3-4):212-8. doi: 10.1016/j.brainresbull.2011.03.024. Epub 2011 Apr 5.
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 (Aβ) 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 Aβ-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 Aβ(25-35), whereas Bax expression and cytochrome c release decreased. Interestingly, these effects of puerarin against Aβ(25-35) insult were abolished by wortmannin, an inhibitor of PI3K phosphorylation. These findings suggest that puerarin prevent Aβ-induced neurotoxicity through inhibiting neuronal apoptosis, and might be a potential preventive or therapeutic agent for AD.
流行病学数据表明，雌激素替代疗法（ERT）可以降低患阿尔茨海默病（AD）的风险。植物雌激素已被提议作为 ERT 的潜在替代品。本研究旨在评估葛根素（一种从葛根中分离出的植物雌激素）对β-淀粉样蛋白（Aβ）毒性的神经保护作用，以及探讨 Akt 激活和促凋亡和抗凋亡蛋白调节在葛根素诱导的神经保护中的作用。本研究表明，葛根素通过抑制 PC12 细胞中的细胞凋亡来提供针对 Aβ诱导的毒性的保护。这一结果也通过激活的 caspase-3 测定得到了证实。在 Aβ（25-35）暴露的 PC12 细胞中用葛根素预处理后，P-Akt、Bcl-2 和 p-Bad 的表达增加，而 Bax 表达和细胞色素 c 释放减少。有趣的是，PI3K 磷酸化抑制剂wortmannin 可消除葛根素对 Aβ（25-35）损伤的这些作用。这些发现表明，葛根素通过抑制神经元凋亡来预防 Aβ诱导的神经毒性，并且可能是 AD 的一种潜在的预防或治疗剂。
