Chair and Department of Pharmacognosy with Medicinal Plant Unit, Medical University in Lublin, 20-093 Lublin, Poland
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland
Int J Mol Sci. 2017 Nov 24;18(12):2511. doi: 10.3390/ijms18122511.
Civilization diseases associated with memory disorders are important health problems occurring due to a prolonged life span. The manuscript shows the results of an in vivo study targeting the emergence of two drug candidates with anti-amnestic properties. The preceding quantitative structure-activity relationship (QSAR) studies provided information on the ability of berberine and magnoflorine to cross the blood-brain barrier (BBB). In the light of these findings, both compounds were purified from crude plant extracts of barberries: berberine-from using a method published earlier, and magnoflorine-from by centrifugal partition chromatography (solvent system: ethyl acetate:butanol:water-0.6:1.5:3 //). Both the compounds were evaluated for their memory enhancing and scopolamine inhibitory properties in an in vivo passive avoidance (PA) test on mice towards short-term and long-term memory. Cognition enhancing properties were observed at the following doses: 5 mg/kg (i.p.) for berberine and 20 mg/kg (i.p.) for magnoflorine. In addition, both the tested isoquinolines with the co-administered scopolamine were found to block long-term but not short-term memory impairment. No influence on the locomotor activity was observed for the tested doses. The results confirmed a marked central activity of magnoflorine and showed the necessity to lower the dosage of berberine. Optimized purification conditions have been elaborated for magnoflorine.
与记忆障碍相关的文明病是由于寿命延长而产生的重要健康问题。本文展示了一项针对两种具有抗遗忘特性的候选药物的体内研究结果。先前的定量构效关系(QSAR)研究提供了小檗碱和厚朴酚穿越血脑屏障(BBB)能力的信息。基于这些发现,从欧洲菝葜的粗提物中分离出这两种化合物:小檗碱-用先前发表的方法从 中提取,厚朴酚-用离心分配色谱(溶剂系统:乙酸乙酯:正丁醇:水-0.6:1.5:3 //)从 中提取。在体内小鼠被动回避(PA)试验中,对两种化合物的增强记忆和东莨菪碱抑制特性进行了评估,以评估短期和长期记忆。在以下剂量下观察到认知增强特性:5 mg/kg(ip)的小檗碱和 20 mg/kg(ip)的厚朴酚。此外,与东莨菪碱共同给予的两种测试异喹啉类化合物均被发现可阻断长期但不阻断短期记忆损伤。测试剂量对运动活性没有影响。结果证实了厚朴酚的明显中枢活性,并表明需要降低小檗碱的剂量。已经为厚朴酚制定了优化的纯化条件。