Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
Cell Mol Neurobiol. 2009 Dec;29(8):1233-44. doi: 10.1007/s10571-009-9419-x.
Glutamate excitotoxicity is involved in many neurodegenerative diseases including Alzheimer's disease (AD). Attenuation of glutamate toxicity is one of the therapeutic strategies for AD. Wolfberry (Lycium barbarum) is a common ingredient in oriental cuisines. A number of studies suggest that wolfberry has anti-aging properties. In recent years, there is a trend of using dried Wolfberry as food supplement and health product in UK and North America. Previously, we have demonstrated that a fraction of polysaccharide from Wolfberry (LBA) provided remarkable neuroprotective effects against beta-amyloid peptide-induced cytotoxicity in primary cultures of rat cortical neurons. To investigate whether LBA can protect neurons from other pathological factors such as glutamate found in Alzheimer brain, we examined whether it can prevent neurotoxicity elicited by glutamate in primary cultured neurons. The glutamate-induced cell death as detected by lactate dehydrogenase assay and caspase-3-like activity assay was significantly reduced by LBA at concentrations ranging from 10 to 500 microg/ml. Protective effects of LBA were comparable to memantine, a non-competitive NMDA receptor antagonist. LBA provided neuroprotection even 1 h after exposure to glutamate. In addition to glutamate, LBA attenuated N-methyl-D-aspartate (NMDA)-induced neuronal damage. To further explore whether LBA might function as antioxidant, we used hydrogen peroxide (H(2)O(2)) as oxidative stress inducer in this study. LBA could not attenuate the toxicity of H(2)O(2). Furthermore, LBA did not attenuate glutamate-induced oxidation by using NBT assay. Western blot analysis indicated that glutamate-induced phosphorylation of c-jun N-terminal kinase (JNK) was reduced by treatment with LBA. Taken together, LBA exerted significant neuroprotective effects on cultured cortical neurons exposed to glutamate.
谷氨酸兴奋性毒性与包括阿尔茨海默病（AD）在内的许多神经退行性疾病有关。减轻谷氨酸毒性是 AD 的治疗策略之一。枸杞（Lycium barbarum）是东方菜肴中的常见成分。许多研究表明枸杞具有抗衰老特性。近年来，在英国和北美，有将干枸杞用作食品补充剂和保健品的趋势。以前，我们已经证明枸杞多糖（LBA）的一部分在原代培养的大鼠皮质神经元中对β-淀粉样肽诱导的细胞毒性具有显著的神经保护作用。为了研究 LBA 是否可以保护神经元免受 AD 脑中发现的其他病理因素（如谷氨酸）的侵害，我们研究了它是否可以防止谷氨酸在原代培养神经元中引起的神经毒性。通过乳酸脱氢酶测定法和半胱天冬酶-3 样活性测定法检测到的谷氨酸诱导的细胞死亡，被浓度范围为 10 至 500 μg/ml 的 LBA 显著降低。LBA 的保护作用可与非竞争性 NMDA 受体拮抗剂美金刚相媲美。LBA 在暴露于谷氨酸后 1 小时仍提供神经保护。除谷氨酸外，LBA 还减轻了 N-甲基-D-天冬氨酸（NMDA）诱导的神经元损伤。为了进一步探讨 LBA 是否可以作为抗氧化剂发挥作用，我们在这项研究中使用了过氧化氢（H2O2）作为氧化应激诱导剂。LBA 不能减轻 H2O2 的毒性。此外，使用 NBT 测定法，LBA 不能减轻谷氨酸诱导的氧化作用。Western blot 分析表明，LBA 处理可降低谷氨酸诱导的 c-jun N-末端激酶（JNK）磷酸化。总之，LBA 对暴露于谷氨酸的培养皮质神经元具有显著的神经保护作用。
