The effect of chlorogenic acid on learning and memory and acetylchoinesterase activity in rats with cognitive deficit induced by intracerebroventricular streptozotocin

Document Type: Research Paper

Authors

1 Department of Physiology, School of Medicine, Shahed University, Tehran, Iran

2 Neurophysiology Research Center, Shahed University, Tehran, Iran

Abstract

Background and Objective: Chlorogenic acid (CGA) is a major polyphenolic component of coffee. Reduction in the risk of a variety of diseases following CGA consumption has been mentioned in recent studies. The effect of CGA on learning and memory in rats with cognitive deficit induced by intracerebroventricular streptozotocin (STZ) and  acetylchoinesterase (AChE) activity was evaluated in this study.
Materials and Methods: For this purpose, 32 male Wistar rats (250-290 g) were divided into four different groups as: control, control plus CGA, STZ treated group, and CGA-treated STZ group. STZ was injected (bilaterally, 3 mg/kg body weight, on days 1 and 3). CGA was administered through intraperitoneal route at a dose of 50 mg/kg for 14 days started one week after STZ injection. To evaluate the spatial learning and memory, Y maze (alternation behavior) and passive avoidance tests were used. Finally, AChE activity was measured via specific kits in hippocampal homogenate.
Results: CGA-treated STZ group did not show significant improvement in spontaneous alternation behavior as compared to STZ group. In passive avoidance test, there was significant difference between STZ and CGA-treated STZ groups. In the latter group, learning and memory was improved. In STZ group, AChE activity as compared to control group significantly increased and treatment with CGA significantly decreased the levels of AChE.
Conclusion: Administration of CGA can improve learning and memory in passive avoidance test with apparently no improvement of spatial memory. Also, CGA can modulate the AChE activity in the hippocampus. Therefore, these results demonstrate the effectiveness of CGA in preventing part of cognitive deficits caused by ICV STZ in rats and also show its potential in the treatment of neurodegenerative diseases such as Alzheimer’s disease.

Keywords


1.       Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloid-beta metabolism beyond the brain. Nature Reviews Neurology 2017;13(10):612-23.
2.       Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, et al. Alzheimer's disease. Lancet 2016;388(10043):505-17.
3.       Reeta KH, Singh D, Gupta YK. Chronic treatment with taurine after intracerebroventricular streptozotocin injection improves cognitive dysfunction in rats by modulating oxidative stress, cholinergic functions and neuroinflammation. Neurochemistry International 2017;108:146-56.
4.       Chen D. Neuroprotective effect of amorphophallus campanulatus in stz induced alzheimer rat model. African Journal of Traditional, Complementary, and Alternative Medicines 2016;13(4):47-54.
5.       Reeta KH, Singh D, Gupta YK. Edaravone attenuates intracerebroventricular streptozotocin-induced cognitive impairment in rats. European Journal of Neuroscience 2017;45(7):987-97.
6.       de Oliveira JS, Abdalla FH, Dornelles GL, Adefegha SA, Palma TV, Signor C, et al. Berberine protects against memory impairment and anxiogenic-like behavior in rats submitted to sporadic Alzheimer's-like dementia: Involvement of acetylcholinesterase and cell death. NeuroToxicology 2016;57:241-50.
7.       Grieb P. Intracerebroventricular Streptozotocin Injections as a Model of Alzheimer's Disease: in Search of a Relevant Mechanism. Molecular Neurobiology 2016;53(3):1741-52.
8.       Sorial ME, El Sayed N. Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer's disease mouse model: possible involvement of the cholinergic system. Naunyn-Schmiedeberg's Archives of Pharmacology 2017;390(6):581-93.
9.       Kwon SH, Lee HK, Kim JA, Hong SI, Kim HC, Jo TH, et al. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. European Journal of Pharmacology 2010;649(1-3):210-7.
 10.    Stefanello N, Schmatz R, Pereira LB, Rubin MA, da Rocha JB, Facco G, et al. Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats. Molecular and Cellular Biochemistry 2014;388(1-2):277-86.
11.    Santana-Galvez J, Cisneros-Zevallos L, Jacobo-Velazquez DA. Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome. Molecules 2017;22(3).
12.    Heitman E, Ingram DK. Cognitive and neuroprotective effects of chlorogenic acid. Nutritional Neuroscience 2017;20(1):32-9.
13.    Baluchnejadmojarad T, Roghani M. Effect of naringenin on intracerebroventricular streptozotocin-induced cognitive deficits in rat: a behavioral analysis. Pharmacology 2006;78(4):193-7.
14.    Balmus IM, Lefter R, Ciobica A, Antioch I, Ababei D, Dobrin R. Preliminary Data on Some Behavioral Changes Induced by Short-Term Intraperitoneal Oxytocin Administration in Aged Rats. Psychiatria Danubina 2018;30(1):91-8.
15.    Ellman GL, Courtney KD, Andres V, Jr., Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology 1961;7:88-95.
16.    Jang YJ, Kim J, Shim J, Kim CY, Jang JH, Lee KW, et al. Decaffeinated coffee prevents scopolamine-induced memory impairment in rats. Behavioral Brain Research 2013;245:113-9.
17.    Kumar M, Kaur D, Bansal N. Caffeic Acid Phenethyl Ester (CAPE) Prevents Development of STZ-ICV Induced dementia in Rats. Pharmacognosy Magazine 2017;13(Suppl 1):S10-s5.