Huanood Gegentuya, Swamy Mahadeva M M, Sasaki Rina, Shimamori Keiya, Kuragano Masahiro, Enkhbat Enkhmaa, Suga Yoshiko, Anetai Masaki, Monde Kenji, Tokuraku Kiyotaka
Graduate School of Engineering, Muroran Institute of Technology, Muroran 050-8585, Japan.
Faculty of Advanced Life Science, Hokkaido University, Sapporo 001-0021, Japan.
Foods. 2024 Nov 22;13(23):3740. doi: 10.3390/foods13233740.
Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease hallmarked by amyloid plaques and neurofibrillary tangles. Amyloid plaques are formed by the amyloid β (Aβ) aggregation, so substances that inhibit this aggregation are useful for preventing and treating AD. Mushrooms are widely used medicinal fungi with high edible and nutritional value. Mushrooms have a variety of biologically active ingredients, and studies have shown that they have certain effects in anti-bacterial, anti-oxidation, anti-inflammatory, anti-tumor, and immune regulation. Previously, we developed a microliter-scale high-throughput screening (MSHTS) system using quantum dot (QD) nanoprobes to screen Aβ aggregation inhibitors. In this study, we appraised the Aβ aggregation inhibitory activity of 210 natural mushrooms from Hokkaido (Japan) and found 11 samples with high activity. We then selected and for extraction and purification as these samples were able to suppress Aβ-induced neurocytotoxicity and were readily available in large quantities. We found that the ethyl acetate (EtOAc) extract of has high Aβ aggregation inhibitory activity, so we performed silica gel column chromatography fractionation and found that fraction 5 (f5) of the EtOAc extract displayed the highest Aβ aggregation inhibitory activity among all mushroom samples. The half-maximal effective concentration (EC) value was 2.30 µg/mL, higher than the EC of 10.7 µg/mL for rosmarinic acid, a well-known Aβ aggregation inhibitor. This inhibitory activity decreased with further purification, suggesting that some compounds act synergistically. The f5 fraction also inhibited the deposition of Aβ aggregates on the cell surface of human neuroblastoma SH-SY5Y cells. Our expectation is that f5, with additional tests, may eventually prove to be an inhibitor for the prevention of AD.
阿尔茨海默病（AD）是一种高度流行的神经退行性疾病，其特征为淀粉样斑块和神经原纤维缠结。淀粉样斑块由淀粉样β（Aβ）聚集形成，因此抑制这种聚集的物质可用于预防和治疗AD。蘑菇是广泛使用的药用真菌，具有很高的食用和营养价值。蘑菇含有多种生物活性成分，研究表明它们在抗菌、抗氧化、抗炎、抗肿瘤和免疫调节方面具有一定作用。此前，我们开发了一种使用量子点（QD）纳米探针的微升规模高通量筛选（MSHTS）系统来筛选Aβ聚集抑制剂。在本研究中，我们评估了来自日本北海道的210种天然蘑菇的Aβ聚集抑制活性，发现11个具有高活性的样本。然后我们选择并 进行提取和纯化，因为这些样本能够抑制Aβ诱导的神经细胞毒性且易于大量获取。我们发现 的乙酸乙酯（EtOAc）提取物具有高Aβ聚集抑制活性，因此我们进行了硅胶柱色谱分离，发现EtOAc提取物的第5部分（f5）在所有蘑菇样本中显示出最高的Aβ聚集抑制活性。半数有效浓度（EC）值为2.30 µg/mL，高于著名的Aβ聚集抑制剂迷迭香酸的EC值10.7 µg/mL。随着进一步纯化，这种抑制活性降低，表明一些化合物起协同作用。f5部分还抑制了Aβ聚集体在人神经母细胞瘤SH-SY5Y细胞表面的沉积。我们期望经过进一步测试，f5最终可能被证明是一种预防AD的抑制剂。 （注：原文中“然后我们选择并 进行提取和纯化”这里有信息缺失，翻译时保留了原文的不完整性）
