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Influence of Hypericum perforatum extract and its single compounds on amyloid-beta mediated toxicity in microglial cells

机译:贯叶连翘提取物及其单一化合物对淀粉样β介导的小胶质细胞毒性的影响

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As immunocompetent cells of the brain, microglia are able to counteract the damaging effects of amyloid-beta in Alzheimer's disease by phagocytosis-mediated clearance of protein aggregates. The survival and health of microglia are therefore critical for attenuating and preventing neurodegenerative diseases. In a microglial cell line pretreated with St. John's wort (Hypericum perforatum L.) extract (HPE), the cell death evoked by treatment with amyloid-beta (25-35) and (1-40) was attenuated significantly in a dose-dependent manner. Investigation of the single compounds in the extract revealed that the flavanols (+)-catechin and (-)-epicatechin increase cell viability slightly, whereas the flavonol quercetin and its glycosides rutin, hyperosid and quercitrin showed no effect on cell viability. In contrast, at the same concentration, the flavonoids reduced the formation of amyloid-induced reactive oxygen species in microglia, indicating that improvement of cell viability by the catechins is not correlated to the antioxidant activity. No influence of HPF on the capacity of microglia to phagocytose sub-toxic concentrations of fibrillar amyloid-beta (1-40) was observed. Other experiments showed that HPE, (+)-catechin and (-)-epicatechin can alter cellular membrane fluidity and thereby may have a beneficial effect on cell health. Our findings provide in vitro evidence that treatment especially with the complex plant extract HPE may restore or improve microglial viability and thereby attenuate amyloid-beta mediated toxicity in Alzheimer's disease. (C) 2007 Elsevier Inc. All rights reserved.
机译:小胶质细胞是大脑中具有免疫功能的细胞,能够通过吞噬作用介导的蛋白质聚集物的清除,抵消阿尔茨海默氏病中β淀粉样蛋白的破坏作用。因此,小胶质细胞的存活和健康对于减轻和预防神经变性疾病至关重要。在用圣约翰草(Hypericum perforatum L.)提取物(HPE)预处理的小胶质细胞系中,用β-淀粉样蛋白(25-35)和(1-40)处理诱发的细胞死亡剂量显着减轻。依赖方式。对提取物中的单一化合物进行的研究表明,黄烷醇(+)-儿茶素和(-)-表儿茶素略微增加细胞活力,而黄酮槲皮素及其糖苷芦丁,高糖苷和槲皮苷对细胞活力没有影响。相反,在相同浓度下,类黄酮减少了小胶质细胞中淀粉样蛋白诱导的活性氧物种的形成,表明儿茶素对细胞活力的改善与抗氧化活性无关。没有观察到HPF对小胶质细胞吞噬纤维状淀粉样蛋白β(1-40)的亚毒性浓度的能力的影响。其他实验表明,HPE,(+)-儿茶素和(-)-表儿茶素可以改变细胞膜的流动性,从而可能对细胞健康产生有益的影响。我们的发现提供了体外证据,表明特别是用复杂植物提取物HPE进行处理可以恢复或改善小胶质细胞的生存力,从而减轻Alzheimer病中β淀粉样蛋白介导的毒性。 (C)2007 Elsevier Inc.保留所有权利。

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