COMPARATIVE EFFECT OF CAFFEINE, CATECHIN AND THEOBROMINE IN SCOPOLAMINE-INDUCED COGNITIVE DYSFUNCTION

Abstract

Tea, coffee and cocoa are consumed in almost all geographical regions of the world due to their psychostimulatory properties and the key compounds present in these beverages are catechin, caffeine and theobromine. However, there is limited information on the compound which best enhances cerebral function. Therefore, this study sought to investigate and compare the effects of catechin, theobromine and caffeine on cognitive function, enzymes and genes linked to the cholinergic, purinergic, monoaminergic, antioxidant systems, and plaque formation in the brain of rats with cognitive dysfunction. The stock concentration of caffeine, catechin and theobromine (1 mg/mL) were prepared according to the standard method and kept at -4°C for subsequent analyses. The antioxidant properties of the compounds were assessed through their radicals [1,1 diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonate radical (ABTS), nitric oxide (NO), and hydroxyl (OH)] scavenging abilities, ferric reducing potentials and their Fe2+ chelating abilities. Also, the effect of the compounds on different prooxidants (FeSO4, cisplatin and sodium nitroprusside) induced lipid peroxidation in rat brain homogenates were assessed. The effects of the compounds on some cholinergic [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and monoaminergic [monoamine oxidase (MAO)] enzymes in rats brain homogenates were also assessed in vitro. Thereafter, the effect of oral administration of caffeine, catechin and theobromine on memory indices, activities of enzymes linked to the cholinergic [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)], purinergic [Adenosine triphosphatidase (ATPdase), Adenosine monophosphatidase (AMPdase), Ecto-nucleotidase (E-NTPdase), monoaminergic (MAO) systems and antioxidant status in rats induced with scopolamine were assessed. Also, quantification of Tau protein and β-amyloid gene expression using reverse transcriptase PCR were determined. The results of replicate experiments were expressed as mean ± standard error of the mean (SEM). The results revealed that the compounds showed antioxidant properties with EC50 values (μg/mL) for caffeine, catechin and theobromine as follow: [DPPH- 245.2 ± 2.0,108.6 ±.0.9,172.4±1.1; ABTS-188.6±.0.8, 177.6±5.1, 132.8±1.3; OH- 294.3±4.0,178.4±1.8,228±2.1; Fe2+- 262.3±6.4,107.5±0.8,197.2±1.7; FRAP- 15.26±0.5,84.59±1.2,34.39±0.7; NO – 299.4±2.6,114.2±3.1,224.9±4.5; MDA iron induced- 175.7±5.2,104.6±6.1,149.3±2.5; MDA cisplatin induced- 156.7±4.6,93.07±0.8,136.9±7.5; and MDA SNP induced-155.7±2.8,93.96±0.9,137.1±3.7) and inhibited the activities of cholinesterases [AChE-175.1±3.2, 183.9±1.7, 151.2±0.8 and BuChE -188.6±2.0, 177.6±2.5, 132.8±4.3 respectively ) in vitro. Futhermore, scopolamine caused a significant decrease (p < 0.05) in cognitive function (as revealed by decreased spatial working memory), nitric oxide level, antioxidant activities (thiols, catalase, SOD, GST and GSH level), with concomitant increase in oxidative stress markers (ROS and MDA) and activities of some enzymes (ADA, ATPdase, AMPdase, MAO, cholinesterases) implicated in cognitive function. However, treatment with caffeine, catechin and theobromine significantly reversed these effects in scopolamine-induced cognitive dysfunction in rats. Findings in this study revealed that these compounds upregulated tau and beta-amyloid genes. Catechin had the highest antioxidant property while theobromine had the best neuroprotective ability amongst the compounds. These findings may provide new insight into the effect of these bioactive compounds as obtained in many foods especially with respect to their antioxidant and neuroprotective effects.