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表征枸杞碱性提取物对β-淀粉样肽神经毒性的神经保护作用。

Characterizing the neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity.

作者信息

Ho Yuen-Shan, Yu Man-Shan, Lai Cora Sau-Wan, So Kwok-Fai, Yuen Wai-Hung, Chang Raymond Chuen-Chung

机构信息

Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR.

出版信息

Brain Res. 2007 Jul 16;1158:123-34. doi: 10.1016/j.brainres.2007.04.075. Epub 2007 May 6.

Abstract

Lycium barbarum is an oriental medicinal herb that has long been used for its anti-aging and cell-protective properties. Previous studies have shown that aqueous extracts from L. barbarum exhibit neuroprotection via inhibiting pro-apoptotic signaling pathways. Other active components can also be accomplished by novel alkaline extraction method, which may give different profiles of water-soluble components. We hypothesize that another active component obtained by alkaline extraction method exerts different biological mechanisms to protect neurons. In this study, we aim to examine the neuroprotective effects from the alkaline extract of L. barbarum, namely LBB, to attenuate beta-amyloid (Abeta) peptide neurotoxicity. Primary cortical neurons were exposed to Abeta-peptides inducing apoptosis and neuronal cell death. Pretreatment of LBB significantly reduced the level of lactate dehydrogenase (LDH) release and the activity of caspase-3 triggered by Abeta. "Wash-out" procedures did not reduce its neuroprotective effects, suggesting that LBB may not bind directly to Abeta. We have further isolated three subfractions from LBB, namely LBB-0, LBB-I and LBB-II. LBB-I and LBB-II showed differential neuroprotective effects. Western blot analysis demonstrated that LBB-I and LBB-II markedly enhanced the phosphorylation of Akt. Taken together, our results suggested that the glycoconjugate isolated from novel alkaline extraction method can open up a new avenue for drug discovery in neurodegenerative diseases.

摘要

枸杞是一种东方药草,长期以来因其抗衰老和细胞保护特性而被使用。先前的研究表明,枸杞的水提取物通过抑制促凋亡信号通路发挥神经保护作用。其他活性成分也可以通过新型碱性提取方法获得,这可能会产生不同的水溶性成分谱。我们假设通过碱性提取方法获得的另一种活性成分发挥不同的生物学机制来保护神经元。在本研究中,我们旨在研究枸杞碱性提取物(即LBB)减轻β-淀粉样蛋白(Aβ)肽神经毒性的神经保护作用。将原代皮质神经元暴露于诱导凋亡和神经元细胞死亡的Aβ肽。LBB预处理显著降低了由Aβ触发的乳酸脱氢酶(LDH)释放水平和半胱天冬酶-3的活性。“洗脱”程序并未降低其神经保护作用,表明LBB可能不直接与Aβ结合。我们进一步从LBB中分离出三个亚组分,即LBB-0、LBB-I和LBB-II。LBB-I和LBB-II表现出不同的神经保护作用。蛋白质印迹分析表明,LBB-I和LBB-II显著增强了Akt的磷酸化。综上所述,我们的结果表明,从新型碱性提取方法中分离出的糖缀合物可为神经退行性疾病的药物发现开辟一条新途径。

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