Department of Medical Biomaterials Engineering, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6732-6. doi: 10.1016/j.bmcl.2013.10.032. Epub 2013 Oct 28.
We isolated 2,3-dihydroxy-4-methoxyacetophenone, a neuroprotective compound from Cynenchum paniculatum in our previous study. The present study was conducted to investigate the possible neuroprotective effect of 2,3-dihydroxy-4-methoxyacetophenone that has been previously isolated from Cynenchum paniculatum on hippocampal neuronal cell line, HT22 cells and its possible cognitive-enhancing effect on scopolamine-induced amnesia in mice. Neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells was evaluated by MTT assay. Also, cognitive enhancing effect against scopolamine (1mg/kg, ip) induced learning and memory deficit was measured by Morris water maze test. Oral administered of 2,3-dihydroxy-4-methoxyacetophenone (1, 10, 20, 40 and 50mg/kg) to amnesic mice induced by scopolamine. In Morris water maze test, 2,3-dihydroxy-4-methoxyacetophenone (50mg/kg) improved the impairment of spatial memory induced by scopolamine. 2,3-Dihydroxy-4-methoxyacetophenone protect HT22 cells on glutamate induced cell-death in a dose-dependent manner (EC50 value: 10.94μM). Furthermore, 2,3-dihydroxy-4-methoxyacetophenone was found to inhibit [Ca(2+)] accumulation in HT22 cells and had antioxidantive activity. The results showed that 2,3-dihydroxy-4-methoxyacetophenone exert neuroprotective and cognitive-enhancing activities through its antioxidant activity. We suggest that 2,3-dihydroxy-4-methoxyacetophenone improves cognitive function and may be helpful for the treatment of Alzheimer's disease.
在我们之前的研究中，从 Cynenchum paniculatum 中分离出了一种具有神经保护作用的化合物 2,3-二羟基-4-甲氧基苯乙酮。本研究旨在探讨之前从 Cynenchum paniculatum 中分离出的 2,3-二羟基-4-甲氧基苯乙酮对海马神经元细胞系 HT22 细胞的可能神经保护作用及其对东莨菪碱诱导的小鼠认知障碍的可能认知增强作用。通过 MTT 测定法评估了 HT22 细胞对抗谷氨酸诱导的神经毒性的神经保护作用。还通过 Morris 水迷宫试验测定了对东莨菪碱（1mg/kg，ip）诱导的学习和记忆缺陷的认知增强作用。通过 Morris 水迷宫试验，腹腔注射东莨菪碱（1、10、20、40 和 50mg/kg）后，2,3-二羟基-4-甲氧基苯乙酮（50mg/kg）改善了东莨菪碱诱导的空间记忆损伤。2,3-二羟基-4-甲氧基苯乙酮以剂量依赖性方式保护 HT22 细胞免受谷氨酸诱导的细胞死亡（EC50 值：10.94μM）。此外，2,3-二羟基-4-甲氧基苯乙酮被发现可抑制 HT22 细胞中 [Ca(2+)]的积累，并且具有抗氧化活性。结果表明，2,3-二羟基-4-甲氧基苯乙酮通过其抗氧化活性发挥神经保护和认知增强作用。我们建议 2,3-二羟基-4-甲氧基苯乙酮改善认知功能，可能有助于治疗阿尔茨海默病。
