Natural Products Research Center, Korea Institute of Science and Technology , Gangneung, Gangwon-do, Republic of Korea.
Department of Physiology, Sungkyunkwan University School of Medicine , Suwon, Gyeonggi-do, Republic of Korea.
J Agric Food Chem. 2017 Apr 19;65(15):3133-3140. doi: 10.1021/acs.jafc.6b04451. Epub 2017 Apr 5.
Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by the accumulation of neurotoxic β-amyloid (Aβ) peptides, which consequently affects cognitive decline and memory impairment. Current research on AD treatment is actively focusing on the prevention of neurotoxic Aβ peptide accumulation. Monsonia angustifolia is reported to be consumed as an indigenous vegetable in Tanzania. In this study, we investigated the effect of the ethanol (EtOH) extract of M. angustifolia dried ground material on Aβ production and spatial learning ability as protection against AD. The formation of Aβ peptides was significantly reduced in HeLa cells stably transfected with the Swedish mutant form of β-amyloid precursor protein (APPsw) after treatment with a 60% EtOH extract of M. angustifolia. We next examined the cognitive-improving effects of the EtOH extract in vivo. Tg2576 mice were treated with extract for 6 months and subjected to Morris water maze and novel object recognition tests. The results showed that the 60% EtOH extract of M. angustifolia significantly ameliorated behavioral deficits of the AD transgenic mice and reduced the level of insoluble Aβ42 in the cerebral cortex and hippocampus. We further found that the 60% EtOH extract was effective for memory function recovery after shorter treatment (4 months). In addition, we isolated and identified several single compounds, justicidin A, 5-methoxyjusticidin A, chinensinaphthol, retrochinensinaphthol methyl ether, and suchilactone, from M. angustifolia and tested these compounds. Among them, justicidin A potently decreased the formation of Aβ in APPsw-transfected cells. These data suggest that the 60% EtOH extract of M. angustifolia has the potential to be developed as a treatment of AD. Furthermore, justicidin A may contribute, at least partially, to the Aβ alteration observed with the extract treatment.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是积累神经毒性β-淀粉样蛋白（Aβ）肽，从而影响认知能力下降和记忆力减退。目前 AD 治疗的研究积极集中在预防神经毒性 Aβ肽积累上。Monsonia angustifolia 据报道在坦桑尼亚被当作一种土生菜食用。在这项研究中，我们研究了 Monsonia angustifolia 干-ground 材料的乙醇（EtOH）提取物对 Aβ 产生和空间学习能力的影响，以预防 AD。在用 Monsonia angustifolia 的 60% EtOH 提取物处理后，稳定转染瑞典突变型β-淀粉样前体蛋白（APPsw）的 HeLa 细胞中 Aβ 肽的形成显著减少。接下来，我们检查了 EtOH 提取物在体内的认知改善作用。用提取物治疗Tg2576 小鼠 6 个月，并进行 Morris 水迷宫和新物体识别测试。结果表明，Monsonia angustifolia 的 60% EtOH 提取物显著改善了 AD 转基因小鼠的行为缺陷，并降低了大脑皮层和海马体中不溶性 Aβ42 的水平。我们进一步发现，60% EtOH 提取物在较短的治疗时间（4 个月）后对记忆功能恢复有效。此外，我们从 Monsonia angustifolia 中分离并鉴定了几种单体化合物，如正义定 A、5-甲氧基正义定 A、琴宁纳醇、返琴宁纳醇甲醚和 suchilactone，并测试了这些化合物。其中，正义定 A 强烈减少了 APPsw 转染细胞中 Aβ的形成。这些数据表明，Monsonia angustifolia 的 60% EtOH 提取物有可能被开发为 AD 的治疗方法。此外，正义定 A 可能至少部分地促成了提取物处理中观察到的 Aβ改变。
