Enhancing cognitive function of healthy Wistar rats with aqueous extract of Centella asiatica

  • Ayeshah A Rosdah Department of Pharmacology, Faculty of Medicine, Universitas Sriwijaya, Palembang
  • Evi Lusiana Department of Pharmacology, Faculty of Medicine, Universitas Sriwijaya, Palembang
  • Muhammad Reagan Department of Internal Medicine, Faculty of Medicine, Universitas Sriwijaya, Palembang
  • Abdurrahman Akib Undergraduate Student, Faculty of Medicine, Universitas Sriwijaya, Palembang
  • Fadhila Khairunnisa Undergraduate Student, Faculty of Medicine, Universitas Sriwijaya, Palembang
  • Afkara Husna Undergraduate Student, Faculty of Medicine, Universitas Sriwijaya, Palembang
Keywords: Centella asiatica, Acetylcholine, Novel object recognition, Cognitive function, Cognitive performance

Abstract

Background: Centella asiatica (L.) Urb is a native herb from Asian countries such as India, China, and Indonesia. This herb has been widely used as a cure for various diseases. However, studies investigating the aqueous extract of Centella asiatica as a nootropic in healthy individuals are still very limited.

Objective: This study aims to investigate the potential of aqueous extract of Centella asiatica in enhancing cognitive function of healthy male Wistar rats.

Methods: Rats were randomly allocated to four treatment groups, i.e. without treatment and aqueous Centella asiatica extract at doses of 200, 400 and 800 mg/kg. To determine enhancement of cognitive function, novel object recognition (NOR) test was conducted after the course of treatment. Acetylcholine content was assessed by enzyme-linked immunosorbent assay.

Results: There was a significantly high preference index towards the novel object in the NOR test in groups treated with 200 mg/kg and 800 mg/kg of the aqueous extract compared to control. This was further confirmed by a significant increase of brain acetylcholine content in rats treated with 200 mg/kg of the extract.

Conclusion: Therefore, this study confirms that the aqueous extract is effective in enhancing cognitive performance of healthy Wistar rats.

References

Jamil SS, Nizami Q, Salam M. Centella asiatica (Linn.) Urban-a review. Nat Prod Radiance. 2007;6(2):158-70.

Gohil K, Patel J, Gajjar A. Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian J Pharm Sci. 2010;72(5):546. https://doi.org/10.4103/0250-474X.78519

Visweswari G, Prasad KS, Chetan PS, Lokanatha V, Rajendra W. Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in pentylenetetrazol-induced seizures with respect to cholinergic neurotransmission. Epilepsy Behav. 2010;17(3):332-5. https://doi.org/10.1016/j.yebeh.2010.01.002

Wijeweera P, Arnason JT, Koszycki D, Merali Z. Evaluation of anxiolytic properties of Gotukola-(Centella asiatica) extracts and asiaticoside in rat behavioral models. Phytomedicine. 2006;13(9):668-76. https://doi.org/10.1016/j.phymed.2006.01.011

Saha A, Bhatia BD, Kulkarni KS. Evaluation of the efficacy of Mentat in children with learning disability: a placebo-controlled double-blind clinical trial. Neurosci Today. 2002;VI(3):184-8.

Wattanathorn J, Mator L, Muchimapura S, Tongun T, Pasuriwong O, Piyawatkul N, et al. Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol. 2008;116(2):325-32. https://doi.org/10.1016/j.jep.2007.11.038

Sari DCR, Aswin S, Susilowati R, Ar-Rochmah M, Prakosa D, Romi M, et al. Ethanol extracts of Centella asiatica leaf improves memory performance in rats after chronic stress via reducing nitric oxide and increasing brain-derived neurotrophic factor (BDNF) concentration. GSTF J Psychol. 2014;1(1). https://doi.org/10.7603/s40790-014-0009-0

Hasselmo ME. The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006;16(6):710-5. https://doi.org/10.1016/j.conb.2006.09.002

Terry A V, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003;306(3):821-7. https://doi.org/10.1124/jpet.102.041616

Nordberg A, Ballard C, Bullock R, Darreh-Shori T, Somogyi M. A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer's disease. Prim care companion CNS Disord. 2013;15(2). https://doi.org/10.4088/PCC.12r01412

Polidori MC, Praticó D, Mangialasche F, Mariani E, Aust O, Anlasik T, et al. High fruit and vegetable intake is positively correlated with antioxidant status and cognitive performance in healthy subjects. J Alzheimer's Dis. 2009;17(4):921-7. https://doi.org/10.3233/JAD-2009-1114

Tildesley NTJ, Kennedy DO, Perry EK, Ballard CG, Wesnes KA, Scholey AB. Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers. Physiol Behav. 2005;83(5):699-709. https://doi.org/10.1016/j.physbeh.2004.09.010

Furey ML, Pietrini P, Haxby J V. Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science (80- ). 2000;290(5500):2315-9. https://doi.org/10.1126/science.290.5500.2315

Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav Brain Res. 1988;31(1):47-59. https://doi.org/10.1016/0166-4328(88)90157-X

Mathiasen JR, DiCamillo A. Novel object recognition in the rat: a facile assay for cognitive function. Curr Protoc Pharmacol. 2010;5.59. 1-5.59. 15. https://doi.org/10.1002/0471141755.ph0559s49

Antunes M, Biala G. The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process. 2012;13(2):93-110. https://doi.org/10.1007/s10339-011-0430-z

De S, Dey YN, Ghosh AK. Phytochemical investigation and chromatographic evaluation of the different extracts of tuber of Amorphaphallus paeoniifolius (Araceae). Int J Pharm Biol Res. 2010;1(5):150-7.

Jared SR. Enhancement of memory in rats with Centella asiatica. Biomed Res. 2010;21(4).

Rao KGM, Rao MS, Rao GS. Evaluation of amygdaloid neuronal dendritic arborization enhancing effect of Centella asiatica (Linn) fresh leaf extract in adult rats. Chin J Integr Med. 2012;1-6.

Venkata SBP, Kanniappan L, Ramakishnaiyah RB, Sundaresan UMM, Mohan SK. Evaluation of the neuroprotective effects of Centella asiatica against scopolamine induced cognitive impairment in mice. Indian J Pharm Educ Res. 2014;48(4):31-4. https://doi.org/10.5530/ijper.48.4.5

Rao KGM, Rao SM, Rao SG. Centella asiatica (linn) induced behavioural changes during growth spurt period in neonatal rats. Neuroanatomy. 2005;4:18-23.

Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study'recognition memory'. Nat Protoc. 2006;1(3):1306. https://doi.org/10.1038/nprot.2006.205

Rao MS. Neuroprotective effect of Centella asiatica leaves extract on substantia Nigra neurons-a quantitative study in mice. Indian J Clin Anat Physiol. 2016;3(4):440-4. https://doi.org/10.5958/2394-2126.2016.00100.6

Mathew M, Subramanian S. In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders. PLoS One. 2014;9(1):e86804. https://doi.org/10.1371/journal.pone.0086804

Zhang X, Wu J, Dou Y, Xia B, Rong W, Rimbach G, et al. Asiatic acid protects primary neurons against C 2-ceramide-induced apoptosis. Eur J Pharmacol. 2012;679(1):51-9. https://doi.org/10.1016/j.ejphar.2012.01.006

James JT, Dubery IA. Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules. 2009;14(10):3922-41. https://doi.org/10.3390/molecules14103922

Long HS, Stander MA, Van Wyk B-E. Notes on the occurrence and significance of triterpenoids (asiaticoside and related compounds) and caffeoylquinic acids in Centella species. South African J Bot. 2012;82:53-9. https://doi.org/10.1016/j.sajb.2012.07.017

Orhan IE, Atasu E, Senol FS, Ozturk N, Demirci B, Das K, et al. Comparative studies on Turkish and Indian Centella asiatica (L.) Urban (gotu kola) samples for their enzyme inhibitory and antioxidant effects and phytochemical characterization. Ind Crops Prod. 2013;47(Supplement C):316-22. https://doi.org/10.1016/j.indcrop.2013.03.022

Randriamampionona D, Diallo B, Rakotoniriana F, Rabemanantsoa C, Cheuk K, Corbisier A-M, et al. Comparative analysis of active constituents in Centella asiatica samples from Madagascar: Application for ex situ conservation and clonal propagation. Fitoterapia. 2007;78(7):482-9. https://doi.org/10.1016/j.fitote.2007.03.016

Greig NH, Utsuki T, Ingram DK, Wang Y, Pepeu G, Scali C, et al. Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent. Proc Natl Acad Sci U S A. 2005;102(47):17213-8. https://doi.org/10.1073/pnas.0508575102

Reid GA, Chilukuri N, Darvesh S. Butyrylcholinesterase and the cholinergic system. Neuroscience. 2013;234:53-68. https://doi.org/10.1016/j.neuroscience.2012.12.054

Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, et al. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radic Biol Med. 2008;45(3):295-305. https://doi.org/10.1016/j.freeradbiomed.2008.04.008

Rendeiro C, Rhodes JS, Spencer JPE. The mechanisms of action of flavonoids in the brain: direct versus indirect effects. Neurochem Int. 2015;89:126-39. https://doi.org/10.1016/j.neuint.2015.08.002

Tousoulis D, Kampoli A-M, Tentolouris Nikolaos Papageorgiou C, Stefanadis C. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol. 2012;10(1):4-18. https://doi.org/10.2174/157016112798829760

Pittella F, Dutra RC, Junior DD, Lopes MTP, Barbosa NR. Antioxidant and cytotoxic activities of Centella asiatica (L) Urb. Int J Mol Sci. 2009;10(9):3713-21. https://doi.org/10.3390/ijms10093713

Tewari D, Mukhopadhyay M, Nekkanti MS, Vallabhaneni S, Sahu G, Jetti SK, et al. Cytoprotective effect of Centella asiatica is mediated through the modulation of mitochondrial voltage-dependent anion channel (VDAC) and scavenging of free radicals. J Funct Foods. 2016;21(Supplement C):301-11. https://doi.org/10.1016/j.jff.2015.11.047

Published
2018-12-31
How to Cite
Rosdah, A. A., Lusiana, E., Reagan, M., Akib, A., Khairunnisa, F., & Husna, A. (2018). Enhancing cognitive function of healthy Wistar rats with aqueous extract of Centella asiatica. Acta Biochimica Indonesiana, 1(2), 37-45. https://doi.org/10.32889/actabioina.v1i2.15