In vitro anti-cholinesterase activity and in vivo screening of Coccoloba uvifera, Mimusops elengi and Syzygium aqueum extracts on learning and memory function of chronic cerebral hypoperfusion rat

Abstract

Vascular dementia (VaD), is one of the most common types of dementia in the ageing population, initiated by chronic cerebral hypoperfusion (CCH). At present, effective therapeutic approaches to cure VaD are still missing. Cholinergic system dysfunction in the central nervous system (CNS) has been recognised as one of the main reasons for learning and memory impairment in VaD patients. Therefore, medications that restore the level of acetylcholine (ACh) neurotransmitter by inhibiting cholinesterase activity were proposed as a potential candidate to treat VaD patients. Permanent occlusion of bilateral common carotid arteries (POBCCA) surgery method was performed to develop CCH model in rats. The present study evaluated the anti-cholinesterase activity of three Malaysian plant methanol leaf extracts in vitro and further validated its cognitive-enhancing effects in vivo using POBCCA rats. The selected plant extracts were Coccoloba uvifera (stems), Mimusops elengi (leaves) and Syzygium aqueum (leaves). The in vitro anti-cholinesterase activities of these plants were determined using Ellman's method. The effects of selected plant extracts (100 and 200 mg/kg, p.o.) on learning and memory functions were evaluated using a series of behavioural tests. All the selected plant extracts exhibited good anti-acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in vitro, with IC50 ranging from 3.67 to 16.04 and 5.6 to 13.95 µg/mL, respectively. Extracts of S. aqueum (200 mg/kg) improve both short- and long-term recognition memories, whereas M. elengi and S. aqueum (200 mg/kg) extracts improve spatial learning. None of the extracts impaired motor and exploratory functions in POBCCA rats. In conclusion, methanol extracts of C. uvifera, M. elengi and S. aqueum showed good anti-cholinesterase activity in vitro. However, only M. elengi and S. aqueum improve learning and memory function in POBCCA rats.