Rutin ameliorates scopolamine-induced learning and memory impairments through enhancement of antioxidant defense system and cholinergic signaling

Drug Metab Pers Ther. 2020 Sep 30:/j/dmdi.ahead-of-print/dmdi-2020-0118/dmdi-2020-0118.xml. doi: 10.1515/dmdi-2020-0118. Online ahead of print.

Abstract

Objectives The brain's cholinergic system occupies a central role in normal cognition and age-related cognitive decline, including Alzheimer's disease (AD). This study sought to investigate the role of antioxidant defense and cholinergic systems on rutin-induced antiamnesia in mice. Methods Rutin (1, 5, or 50 mg/kg, p.o.) or vehicle (10 ml/kg, p.o.) was administered for three consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg, i.p) was given, 5 min post-scopolamine injection, open field, Y-maze, or Morris water maze (MWM) (five days consecutive training sessions) tasks was carried out. The mice were sacrificed on day 7 to assays for biomarkers of oxidative stress and cholinergic system. Results Scopolamine significantly reduced spontaneous alternation behavior in Y-maze and prolonged escape latency in MWM tasks when compared to vehicle-treated control indicative of working memory and spatial learning deficits. However, the pretreatment of mice with rutin (1, 5, or 50 mg/kg) prevented scopolamine-induced working memory and spatial learning impairments without affecting spontaneous locomotor activity. Scopolamine-induced nitrosative/oxidative stress and increased acetylcholinesterase activity in the prefrontal cortex and hippocampus were significantly attenuated by the pretreatment of mice with rutin. Conclusions rutin restored cognitive function in scopolamine-induced amnesia through enhancement of antioxidant defense and cholinergic systems.

Keywords: Morris water maze; Y-maze; amnesia; cholinergic dysfunction; hippocampus; oxidative stress.