Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 08826 , Republic of Korea.
Division of Biological Science and Technology , Yonsei University , Wonju 220-100 , Republic of Korea.
J Nat Prod. 2019 May 24;82(5):1128-1138. doi: 10.1021/acs.jnatprod.8b00841. Epub 2019 Apr 22.
In Alzheimer's disease, amyloid-β (Aβ) accumulation in the brain results in neuronal cell death and is one of the major causes of dementia. Because the current therapeutic agents are not yet sufficiently effective or safe, there have been attempts to find new neuroprotective chemicals against Aβ-induced cytotoxicity. A 70% EtOH extract of whole plants of Ambrosia artemisiifolia (common ragweed) was selected after the screening of a natural extract library. Seven new eudesmane-type glycosides (1-7) and seven known compounds (8-14) were obtained through bioactivity-guided fractionation from the aerial parts of this plant. Their structures were determined on the basis of their nuclear magnetic resonance spectra, high-resolution electrospray ionization mass spectrometry analysis, and electronic circular dichroism calculations. Among them, compounds 1, 2, 4-6, 8, 9, 11, 13, and 14 showed protective effects against Aβ-induced cytotoxicity in Aβ-transfected HT22 cells. The most active compounds, 5 and 6, exhibited moderate protective activity dose-dependently (10, 20, and 40 μM).
在阿尔茨海默病中，大脑中淀粉样蛋白-β（Aβ）的积累导致神经元细胞死亡，是痴呆症的主要原因之一。由于目前的治疗药物还不够有效或安全，因此人们一直在尝试寻找针对 Aβ 诱导的细胞毒性的新的神经保护化学物质。通过对天然提取物文库进行筛选，选择了全株蒿（普通豚草）的 70%乙醇提取物。从该植物的地上部分通过基于生物活性的分离，获得了七个新的倍半萜型糖苷（1-7）和七个已知化合物（8-14）。基于其核磁共振谱、高分辨电喷雾电离质谱分析和电子圆二色性计算确定了它们的结构。其中，化合物 1、2、4-6、8、9、11、13 和 14 对 Aβ 转染的 HT22 细胞中的 Aβ 诱导的细胞毒性具有保护作用。最活跃的化合物 5 和 6 表现出适度的保护活性，呈剂量依赖性（10、20 和 40 μM）。
