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

Abstract

ObjectivesThe 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.MethodsRutin (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.ResultsScopolamine 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.Conclusionsrutin restored cognitive function in scopolamine-induced amnesia through enhancement of antioxidant defense and cholinergic systems.

Role of Cholinergic Signaling in Alzheimer’s Disease

“…Scopolamine has been used in many research studies to explore and identify therapeutic targets for AD [ 71 ]. Rutin improves cognitive dysfunction in scopolamine-induced amnesia by enhancing antioxidant defense and cholinergic systems [ 133 ]. 7,3′,4′-trihydroxy isoflavones (THIF) can effectively improve the memory impairment induced by scopolamine in mice.…”

Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer’s Disease: A Review

“…Notably, the newly detected flavonoids in mung bean sprouts, including rutin, isoquercitrin, and isorhamnetin, also showed neuroprotective activity against AD (as shown in Table ). Specifically, rutin was reported to improve the learning and memory deficits in various AD models, including APP/PS1 double transgenic mice and Tau-P301S mice, as well as STZ or scopolamine-induced models. − The neuroprotective mechanisms of rutin were found to be the inhibition of oxidative stress, neuroinflammation, Aβ oligomerization and fibrillization, tau pathology, and AChE activity. − As for isoquercitrin, it reduced the memory and learning deficits and hippocampal neural damages induced by STZ injection (i.c.v.) through inhibiting apoptosis and oxidative stress as well as promoting neurite outgrowth, a biomarker for the recovery of neuronal function .…”

Cajanus cajan (L) Millsp. seed extract ameliorated scopolamine-induced amnesia through increase in antioxidant defense mechanisms and cholinergic neurotransmission

“…Alzheimer's disease (AD), a progressive and debilitating neurodegenerative disorder is one of the most common causes of dementia in the elderly and more than 40 million people are living with AD worldwide (Francis et al, 1999;Khurana et al, 2021). The main aetiology of AD remains elusive, however, several hypothesis have been postulated to be involved in the pathophysiology of AD amongst which are oxidative stress, neuroin ammation (Tonnies and Trushina 2017; Bondi et al, 2017), and loss of the cholinergic innervation in the limbic and neocortical region of the brain (Hampel et al, 2018;Ishola et al, 2020). The cholinergic hypothesis has gained signi cant attention over the years.…”

“…It is worthy of note that the current pharmacological interventions in the management of AD only proffer symptomatic relieve through enhancement of cholinergic neurotransmission and blockade of NMDA receptor (Ishola et al, 2019). ROS-induced oxidative damage in the hippocampus and neocortex are well linked with aging and AD development, thus, antioxidants could be a viable option in the management of AD, hence, slowing the progression of AD (Ishola et al, 2020). Interestingly, avonoids are antioxidant and are very ubiquitous in plants with various health bene t including prevention of neurodegenerative diseases (Wan et al, 2019;Ishola et al, 2020).…”

“…ROS-induced oxidative damage in the hippocampus and neocortex are well linked with aging and AD development, thus, antioxidants could be a viable option in the management of AD, hence, slowing the progression of AD (Ishola et al, 2020). Interestingly, avonoids are antioxidant and are very ubiquitous in plants with various health bene t including prevention of neurodegenerative diseases (Wan et al, 2019;Ishola et al, 2020).…”