Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
Phytomedicine. 2010 Jul;17(8-9):698-701. doi: 10.1016/j.phymed.2009.10.003. Epub 2009 Dec 6.
The treatment of neurological disorders and neurodegenerative diseases is related to the levels of acetylcholine (ACh) through the inhibition of acetylcholinesterase (AChE). Galanthamine, an important alkaloid isolated from the Amaryllidaceae family, is approved for the pharmacological treatment of Alzheimer's disease (AD) and acts by inhibiting the acetylcholinesterase (AChE) activity. In the present study, Ellman's method was used to verify the inhibition of AChE activity of some isoquinolines alkaloids such as galanthamine, montanine, hippeastrine and pretazettine. At the concentrations 1mM, 500 microm and 100 microm, galanthamine presented an AChE inhibition higher than 90%. Montanine inhibited, in a dose-dependent manner, more than 50% of the enzyme at 1mM concentration. With the concentrations 500 microm and 100 microm, 30-45% of AChE activity inhibition was detected. The alkaloids hippeastrine and pretazettine presented no significant inhibition of the AChE activity. The results demonstrate that montanine significantly inhibits AChE activity at the tested concentrations, suggesting the necessity of further investigations on this alkaloid use in treating neurological disorders.
神经紊乱和神经退行性疾病的治疗与乙酰胆碱(ACh)的水平有关,通过抑制乙酰胆碱酯酶(AChE)来实现。加兰他敏是从石蒜科植物中分离得到的一种重要生物碱,已被批准用于治疗阿尔茨海默病(AD),通过抑制乙酰胆碱酯酶(AChE)的活性发挥作用。在本研究中,采用 Ellman 法验证了几种异喹啉生物碱如加兰他敏、麦角胺、小檗碱和普塔嗪的 AChE 活性抑制作用。在 1mM、500μm 和 100μm 的浓度下,加兰他敏对 AChE 的抑制率高于 90%。麦角胺在 1mM 浓度下以剂量依赖性方式抑制超过 50%的酶。在 500μm 和 100μm 的浓度下,检测到 30-45%的 AChE 活性抑制。生物碱小檗碱和普塔嗪对 AChE 活性没有明显的抑制作用。结果表明,麦角胺在测试浓度下显著抑制 AChE 活性,表明有必要进一步研究这种生物碱在治疗神经紊乱方面的应用。