Nasal Administration of Quercetin Liposomes Modulate Cognitive Impairment and Inhibit Acetylcholinesterase Activity in Hippocampus

Problem statement: Oxidative stress is a major factor implicated in the degeneration of cholinergic neurons in Alzheimer’s Disease (AD). Several reports have indicated that antioxidant intake is beneficial to delay or inhibit the progression of this disease. Presently, Acetylcholinesterase (AChE) inhibitors are the mainstay of therapy for AD. Quercetin, one of the flavonoids in fruits and vegetables, has a powerful antioxidant activity both in vitro and in vivo. However, the potential of quercetin as Acetylcholinesterase (AChE) inhibitors, an important aspect for neuroprotection, has not been properly investigated. Approach: This study was designed to evaluate the anti-cholinesterase activity and improves cognitive function of quercetin liposomes via nasal administration in a rat AF64A injection model of AD. Male Wistar rats were pretreated with quercetin liposomes, containing 0.5 mg of quercetin in 20 µL via intranasal route once daily continually for 3 weeks. Learning and memory was evaluated using the Morris water maze test at 7 days after the lesioning and then the rats were sacrificed for determining the contents of Acetylcholinesterase (AChE), the activities of Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Malondialdehide (MDA), a lipid peroxidation product in the hippocampus. Results: AF64A with nasal administration of free liposomes showed the loss of cognitive performance in Morris water maze test, increase in the markers of oxidative damage (MDA, SOD and GPX) and the AChE activity in the hippocampus. However, AF64A with nasal administration of quercetin liposomes reversed all the parameters significantly. Conclusion: Our studies demonstrated that quercetin liposomes via nasal administration may have a therapeutic importance in the clinical management of Alzheimer’s disease.