ABSTRACT
Neurodegenerative diseases are mostly age-related diseases characterized by memory loss, cognitive dysfunctions, neuronal damage, and death. The pathogenesis of neurodegenerative diseases is fairly understood. However, it’s regarded as a multifactorial disorder involving complex mechanisms. This study therefore evaluated the neuroprotective potential of chlorogenic acid (5 and 10 mg/kgbw), quercetin (5 and 10 mg/kgbw) and the standard drug donepezil (5 mg/kgbw) on some biochemical indices linked with neurodegenerative disorders in scopolamine-induced (1.4 mg/kgbw) amnesia in rats. Three (3) modes of administration were employed in this study viz: preadministration, co-administration and post-administration. The study entailed in vitro assessment of antioxidant properties of chlorogenic acid and quercetin using standard antioxidant models. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activities were evaluated in isolated rats’ brain tissue homogenates. Behavioural (Y-Maze and Morris Water Maze) tests in scopolamine exposed rats were determined. Enzymatic and non-enzymatic antioxidants and neurological function parameters were estimated. Histopathology examination of sections of the brain tissue were examined using a light microscope, molecular docking (in silico) evaluating molecular interaction of the test compounds on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO), ecto-5' nucleotidase (E-NTDase) and adenosine deaminase (ADA) enzymes were determined. Results showed that chlorogenic acid scavenged DPPH, NO*, ABTS* and OH* radicals as well as chelated Fe2+ better than quercetin and ascorbic acid standard as confirmed by their respective EC50. Chlorogenic acid significantly (p < 0.05) inhibited AChE and BChE activities when compared with quercetin and ascorbic acid standard while quercetin inhibited MDA and MAO levels more than chlorogenic acid. The behavioural studies from the Y-maze task increased significantly (p < 0.05) in percentage alternation of scopolamine exposed rats treated with either quercetin or chlorogenic acid (at 5 and 10 mg/kg) respectively when compared with the scopolamine administered rats (negative control). In addition, the Morris water maze study showed a significant (p < 0.05) reduction in the escape latency time of the test compounds treated rats, with chlorogenic acid (at 10mg/kg) being more effective than quercetin in both mazes. Quercetin and chlorogenic acid treated rats exhibited marked (p < 0.05) reduction in total protein concentration, AChE, BChE, MAO, E-NTDase, ALP, ADA, and Na+ /K+ ATPase activities in the striatum, hippocampus and cortex of the brain relative to negative control (Scopolamine-only administered rats) values. Dopamine levels were significantly increased (p < 0.05) by administration of quercetin and chlorogenic acid when compared with the negative control (Scopolamine-only administered rats). Administration of quercetin and chlorogenic acid also resulted in significant increases (p < 0.05) in SOD and catalase activities; total thiols, GSH and decrease in TBARS levels in all the brain sections compared to the negative control with the test compounds recording better results than the donepezil (standard drug). Histopathology results revealed that doses of quercetin and chlorogenic acid reversed the evidence of neurodegeneration to a large extent better than the scopolamine only exposed rats. However, vacuolation and cellular disintegration which denotes signs of neurodegeneration were still observed in the coadministration and post-administration studies in the different brain sections studied. These signs were more observed in the co-administration and post-administration modes. Treatment with quercetin, chlorogenic acid and donepezil gradually reversed signs of neurodegeneration as there were observed reduced vacuolation and cellular disintegration. The in silico study revealed that quercetin, chlorogenic acid and donepezil showed promising molecular interactions with MAO, BChE, AChE, ENTDase and ADA. These findings suggest that quercetin and chlorogenic acid may be useful in the management of oxidative stress-related neurodegeneration.
