Wang Xingyuan, Zhou Longjian, Liu Yayue, Ban Fangfang, Yang Zhiyou, Zhang Yongping, Hu Xueqiong, Zhang Yi
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Laboratory for Marine Biological Products, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Marine Biomedicine R&D Center at Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Zhanjiang, China.
Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China.
Chem Biodivers. 2025 Feb;22(2):e202401809. doi: 10.1002/cbdv.202401809. Epub 2024 Dec 7.
Screening Aβ aggregation inhibitors (AAIs) is important for Alzheimer's disease drug discovery. However, common cellular or biochemical methods are not suitable for high-throughput natural product screening. A gold nanoparticle (GNP) screening method was employed in this study to screen marine fungal crude extracts and pure compounds for quick AAI discovering. The anti-Aβ aggregation activity was further inspected using transmission electron microscopic (TEM) observation, and the interaction between active molecules and different Aβ species was revealed by molecular docking. The results indicated that the fungal extracts DLS2008001(M), BM3T2(M), DLEN2008005(M), TBG1-16(P), and TBG1-13(P) showed activity comparable to the positive control human serum albumin at the concentration of 500 µg/mL; 10 pure compounds also displayed moderate anti-aggregation activity, particularly nidulin, aspergillusidone G, and butyrolactone I. The inspection of anti-Aβ aggregation effect through TEM further demonstrated that extracts TBG1-16(P), DLS2008001(M), and BM3T2(M) dramatically inhibited the formation of Aβ aggregates. Molecular docking displayed low binding energies and key interactions of nidulin, aspergillusidone G, and butyrolactone I, with nine types of Aβ peptides. These findings indicate that the GNP method is efficient in screening AAIs and reveal marine fungal natural products as valuable sources of small molecular AAIs.
筛选β淀粉样蛋白聚集抑制剂（AAIs）对于阿尔茨海默病药物研发至关重要。然而，常见的细胞或生化方法并不适用于高通量天然产物筛选。本研究采用金纳米颗粒（GNP）筛选方法来筛选海洋真菌粗提物和纯化合物，以快速发现AAIs。使用透射电子显微镜（TEM）观察进一步检测抗β淀粉样蛋白聚集活性，并通过分子对接揭示活性分子与不同β淀粉样蛋白种类之间的相互作用。结果表明，真菌提取物DLS2008001(M)、BM3T2(M)、DLEN2008005(M)、TBG1-16(P)和TBG1-13(P)在浓度为500μg/mL时显示出与阳性对照人血清白蛋白相当的活性；10种纯化合物也表现出适度的抗聚集活性，特别是棒曲霉素、曲霉异黄酮G和丁内酯I。通过TEM对抗β淀粉样蛋白聚集作用的检测进一步表明，提取物TBG1-16(P)、DLS2008001(M)和BM3T2(M)显著抑制了β淀粉样蛋白聚集体的形成。分子对接显示棒曲霉素、曲霉异黄酮G和丁内酯I与9种β淀粉样肽具有低结合能和关键相互作用。这些发现表明，GNP方法在筛选AAIs方面是有效的，并揭示了海洋真菌天然产物是小分子AAIs的宝贵来源。
