Alzheimer's disease (AD) is characterized by irreversible and progressive memory loss and has no effective treatment. Recently, many small molecule nature products have been identified with neuroprotective functions and shown beneficial effects to AD patients. In the current study, we thus performed a small scale screening to determine the protective effects of natural compounds on streptozotocin (STZ)‐induced neurotoxicity and Alzheimer's disease (AD). We found that a lead flavonoid compound, isoquercitrin (ISO) display the most effective anti‐cytotoxic activities via inhibiting STZ‐induced apoptosis, mitochondria dysfunction and oxidative stress. Treatment with ISO largely rescues STZ‐induced differentiation inhibition and enhances neurite outgrowth of Neuro2a (N2a) cells in vitro. Moreover, oral administration of ISO protects hippocampal neurons from STZ‐induced neurotoxicity and significantly improves the cognitive and behavioural impairment in STZ‐induced AD rats. In general, our screening identifies ISO as an effective therapeutic candidate against STZ‐induced neurotoxicity and AD‐like changes.

中文翻译：

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异槲皮苷对链脲佐菌素诱导的神经毒性的保护作用。

阿尔茨海默氏病（AD）的特征是不可逆和进行性记忆丧失，并且没有有效的治疗方法。最近，已经鉴定出许多具有神经保护功能的小分子天然产物，并显示出对AD患者有益的作用。因此，在当前的研究中，我们进行了小规模筛选，以确定天然化合物对链脲佐菌素（STZ）诱导的神经毒性和阿尔茨海默氏病（AD）的保护作用。我们发现一种类黄酮化合物，异槲皮苷（ISO）通过抑制STZ诱导的细胞凋亡，线粒体功能障碍和氧化应激，显示出最有效的抗细胞毒活性。使用ISO治疗可在很大程度上拯救STZ诱导的分化抑制并增强Neuro2a（N2a）细胞的神经突向外生长。此外，口服ISO保护海马神经元免受STZ诱导的神经毒性，并显着改善STZ诱导的AD大鼠的认知和行为障碍。一般而言，我们的筛选将ISO视为对抗STZ诱导的神经毒性和AD样变化的有效治疗药物。