The Evaluation of Pro-Cognitive and Antiamnestic Properties of Berberine and Magnoflorine Isolated from Barberry Species by Centrifugal Partition Chromatography (CPC), in Relation to QSAR Modelling

Abstract

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 <i>Berberis siberica</i> using a method published earlier, and magnoflorine-from <i>Berberis cretica</i> by centrifugal partition chromatography (solvent system: ethyl acetate:butanol:water-0.6:1.5:3 <i>v</i>/<i>v</i>/<i>v</i>). 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.