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Mulberry fruit extract alleviates the intracellular amyloid-β oligomer-induced cognitive disturbance and oxidative stress in Alzheimer’s disease model mice
Genes to Cells ( IF 1.3 ) Pub Date : 2021-08-12 , DOI: 10.1111/gtc.12889
Tomoyo Ochiishi 1 , Masami Kaku 2 , Tanwarat Kajsongkram 3 , Krittiya Thisayakorn 3
Affiliation  

Intracellular amyloid-β (Aβ) oligomers are key therapeutic targets because they are strongly cytotoxic and play crucial roles in the cognitive function in Alzheimer's disease (AD). Anthocyanins, polyphenolic flavonoids with antioxidant and neuroprotective properties, are potential therapeutic candidates for AD. Here, we investigated the effects of anthocyanin-enriched extracts from fruits of mulberry (Morus alba Linn.) in Thailand against the neurotoxicity of Aβ oligomers. Using the monitoring system for Aβ aggregation, we showed that the extract induced the dissociation of Aβ in cultured HEK293T cells. To investigate the effects on cognitive function, we orally administered the extract to Aβ-GFP transgenic mice (Aβ-GFP Tg), a mouse model that expresses Aβ oligomers inside neurons, and performed the novel object recognition test and passive avoidance test. Aβ-GFP Tg usually showed deficits in novel object recognition memory and reference memory compared with non-Tg, but administration of the extract improved both compared with vehicle-treated Aβ-GFP Tg. Aβ-GFP Tg exhibited lower superoxide dismutase (SOD) activity than non-Tg. However, after the administration of the extract, the SOD activity was restored. These results suggest that Thai mulberry fruit extract ameliorates cytotoxicity induced by the intracellular Aβ oligomers and may be an effective therapeutic or preventive candidate for AD.

中文翻译:

桑椹提取物减轻阿尔茨海默病模型小鼠细胞内β-淀粉样蛋白寡聚体诱导的认知障碍和氧化应激

细胞内淀粉样蛋白-β (Aβ) 寡聚体是关键的治疗靶点,因为它们具有很强的细胞毒性,并且在阿尔茨海默病 (AD) 的认知功能中起关键作用。花青素是具有抗氧化和神经保护特性的多酚类黄酮类化合物,是 AD 的潜在治疗候选者。在这里,我们研究了桑椹 ( Morus alba ) 果实中富含花青素的提取物的作用。Linn.) 在泰国对抗 Aβ 寡聚体的神经毒性。使用 Aβ 聚集监测系统,我们发现提取物诱导培养的 HEK293T 细胞中 Aβ 的解离。为了研究对认知功能的影响,我们将提取物口服给予 Aβ-GFP 转基因小鼠 (Aβ-GFP Tg),这是一种在神经元内表达 Aβ 寡聚体的小鼠模型,并进行了新的物体识别测试和被动回避测试。与非 Tg 相比,Aβ-GFP Tg 通常在新的物体识别记忆和参考记忆方面表现出缺陷,但与载体处理的 Aβ-GFP Tg 相比,提取物的施用均有所改善。Aβ-GFP Tg 的超氧化物歧化酶 (SOD) 活性低于非 Tg。然而,在施用提取物后,SOD 活性恢复。
更新日期:2021-08-12
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