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首页> 外文期刊>Biotechnology Progress >Study of Neuroprotective Function of Ginkgo biloba Extract (EGb761) Derived-Flavonoid Monomers Using a Three-Dimensional Stem Cell-Derived Neural Model
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Study of Neuroprotective Function of Ginkgo biloba Extract (EGb761) Derived-Flavonoid Monomers Using a Three-Dimensional Stem Cell-Derived Neural Model

机译：使用三维干细胞衍生的神经模型研究银杏提取物（EGb761）衍生的类黄酮单体的神经保护功能

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An in vitro three-dimensional (3D) cell culture system that can mimic organ and tissue structure and function in vivo will be of great benefit for drug discovery and toxicity testing. In this study, the neuroprotective properties of the three most prevalent flavonoid monomers extracted from EGb 761 (isorharmnetin, kaempferol, and quercetin) were investigated using the developed 3D stem cell-derived neural co-culture model. Rat neural stem cells were differentiated into co-culture of both neurons and astrocytes at an equal ratio in the developed 3D model and standard two-dimensional (2D) model using a two-step differentiation protocol for 14 days. The level of neuroprotective effect offered by each flavonoid was found to be aligned with its effect as an antioxidant and its ability to inhibit Caspase-3 activity in a dose-dependent manner. Cell exposure to quercetin (100 mM) following oxidative insult provided the highest levels of neuroprotection in both 2D and 3D models, comparable with exposure to 100 mM of Vitamin E, whilst exposure to isorhamnetin and kaempferol provided a reduced level of neuroprotection in both 2D and 3D models. At lower dosages (10 mM flavonoid concentration), the 3D model was more representative of results previously reported in vivo. The co-cultures of stem cell derived neurons and astrocytes in 3D hydrogel scaffolds as an in vitro neural model closely replicates in vivo results for routine neural drug toxicity and efficacy testing. (C) 2016 American Institute of Chemical Engineers Biotechnol.
机译：可以在体内模拟器官和组织结构与功能的体外三维（3D）细胞培养系统将对药物发现和毒性测试非常有用。在这项研究中，使用发达的3D干细胞衍生的神经共培养模型研究了从EGb 761提取的三种最普遍的类黄酮单体（异海藻素，山奈酚和槲皮素）的神经保护特性。使用两步分化方案，将大鼠神经干细胞在发达的3D模型和标准二维（2D）模型中以相等的比例分化为神经元和星形胶质细胞共培养14天。发现每种类黄酮提供的神经保护作用水平与其作为抗氧化剂的作用及其以剂量依赖性方式抑制Caspase-3活性的能力相吻合。在2D和3D模型中，氧化性损伤后暴露于槲皮素（100 mM）的细胞可提供最高水平的神经保护，与暴露于100 mM的维生素E相当，而暴露于异鼠李素和山emp酚可降低2D和3D模型中的神经保护。 3D模型。在较低的剂量（10 mM的类黄酮浓度）下，3D模型更能代表先前报道的体内结果。干细胞衍生的神经元和星形胶质细胞在3D水凝胶支架中的共培养作为体外神经模型，可以密切复制体内结果，用于常规神经药物毒性和功效测试。 （C）2016美国化学工程师学会生物技术研究所。

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