大量神经系统疾病，包括朊状体病、帕金森病和阿尔茨海默病（AD），被认定为由蛋白质构象、聚集和金属离子失衡引起。近年来，对来自植物和微生物源的天然产物（NPs）的治疗潜力进行了大量的探索和研究，包括对癌症、糖尿病、心血管疾病和神经退行性疾病的治疗。本研究中，我们研究了两种天然产物环独脂醇（CAG）和石榴皮苷（PCG）对金属诱导的Aβ25-35和PrP106-126肽的寡聚化和聚集的影响。我们通过硫膦素- T（ThT）测定法、MALDI-TOF、圆二色CD光谱和透射电子显微镜（TEM）来检测两种天然产物的肽聚集和抑制特性。在这两种天然产物中，PCG与肽显著结合，螯合金属离子（Cu2+和Zn2+），抑制肽聚集，显著减少氧化应激，并控制活性氧物质（ROS）的产生。两种天然产物均具有较低的细胞毒性，并通过共价键和疏水相互作用显著减轻了海马神经元HT-22细胞中由肽介导的细胞毒性。版权所有©2023 Elsevier B.V. 保留所有权利。

Numerous neurological disorders, including prion, Parkinson's, and Alzheimer's disease (AD), are identified as being caused by alterations in protein conformation, aggregation, and metal ion dyshomeostasis. Recent years have seen a significant increase in the exploration and study of natural products (NPs) from plant and microbial sources for their therapeutic potential against several diseases, including cancer, diabetes, cardiovascular disease, and neurodegenerative diseases. In this study, we have examined the effect of two NPs, cycloastragenol (CAG) and punicalagin (PCG), on the metal-induced oligomerization and aggregation of Aβ25-35 and PrP106-126 peptides. The peptide aggregation and inhibitory properties of both NPs were examined by the thioflavin-T (ThT) assay, MALDI-TOF, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM). Among the two NPs, PCG significantly binds to the peptides, chelates metal ions (Cu2+ and Zn2+), inhibits peptide aggregation, substantially reduces oxidative stress, and controls the production of reactive oxygen species (ROS). Both NPs exhibited low cytotoxicity and prominently mitigated peptide-mediated cell cytotoxicity in hippocampal neuronal HT-22 cells by covalent bonding and hydrophobic interactions.Copyright © 2023 Elsevier B.V. All rights reserved.