Laboratory of Pharmacognosy, College of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si 31116, Republic of Korea.
Host Defense Modulation Laboratory, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Molecules. 2023 Jan 19;28(3):1017. doi: 10.3390/molecules28031017.
Alzheimer's disease (AD) is a serious neurodegenerative brain disease that interferes with daily life. The accumulation of beta-amyloid (Aβ), along with oxidative stress-inducing neurocellular apoptosis, has been considered one of the causes of AD. Thus, the purpose of this study is to find natural products that can reduce Aβ accumulation. The ethanol extract of Hu & Cheng fruits (Cupressaceae) significantly reduced the aggregation of Aβ into oligomers and fibrils determined by Thioflavin T (ThT) assay. The solvent-partitioned ethyl acetate layer was further separated based on the bioassay-guided isolation method combined with the ThT assay. As a result, five compounds were isolated and elucidated as taxoquinone (), sugiol (), suginal (), sandaracopimarinol (), and sandaracopimaradien-19-ol () by comparing NMR data with references. All the compounds significantly reduced the aggregation of Aβ and enhanced the disaggregation of pre-formed Aβ aggregates in a dose-dependent manner. Furthermore, the inhibition of Aβ aggregation by the compounds protected PC12 cells from Aβ aggregate-induced toxicity. Among the five compounds, sandaracopimarinol () and sandaracopimaradien-19-ol () were the most effective. These results suggest that and isolated five compounds have a potential for further study to be developed as anti-AD agents.
阿尔茨海默病（AD）是一种严重的神经退行性脑疾病，会干扰日常生活。β-淀粉样蛋白（Aβ）的积累，以及诱导神经细胞凋亡的氧化应激，被认为是 AD 的原因之一。因此，本研究的目的是寻找可以减少 Aβ 积累的天然产物。胡杨果实（柏科）的乙醇提取物通过噻唑蓝（ThT）试验显著减少了 Aβ聚集成寡聚物和原纤维的聚集。根据生物测定指导的分离方法，进一步分离溶剂部分的乙酸乙酯层，并结合 ThT 试验。结果，分离并鉴定出五种化合物为 taxoquinone ()、sugiol ()、suginal ()、sandaracopimarinol () 和 sandaracopimaradien-19-ol ()，通过与参考文献的 NMR 数据比较。所有化合物均显著降低了 Aβ 的聚集，并以剂量依赖的方式增强了预形成的 Aβ 聚集体的解聚。此外，化合物对 Aβ 聚集的抑制作用可保护 PC12 细胞免受 Aβ 聚集诱导的毒性。在这五种化合物中，sandaracopimarinol () 和 sandaracopimaradien-19-ol () 的效果最为显著。这些结果表明和分离的五种化合物具有进一步研究开发成为抗 AD 药物的潜力。
