Ellagic Acid Administration Reverses Colchicine- Induced Dementia in Rats


  • Jaspreet Kaur Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Ropar, Punjab, India
  • Manish Kumar Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Ropar, Punjab, India
  • Nitin Bansal Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Ropar, Punjab, India




Ellagic acid, colchicine, memory, oxidative stress


The late-onset sporadic type of Alzheimer’s disease is characterised by chronic oxidative stress, neuroinflammation and cognitive dysfunction. Ellagic acid is a naturally occurring polyphenol known to possess robust antioxidant property. In the present study, memory enhancing potential of ellagic acid has been explored against ICV colchicine induced dementia in rats. Colchicine (15μg/rat) was administered to Wistar rats (200g) through intracerebroventricular (ICV) route by using stereotaxic apparatus. ICV colchicine induces Alzheimer’s disease like changes in the brain such as rampant free radical production, neuroinflammation and selective neurodegeneration in hippocampus and cortex by acting as an antitubulin agent (mitotic poison). Ellagic acid (17.5 and 35 mg/kg, p.o.) was administered to rats for 25 successive days. Morris water maze and elevated plus maze paradigms were utilized to assess the spatial memory of rats. Oxidative stress biomarkers along with TNF-α were also measured in brain of rats. Ellagic acid prevented the ICV colchicine triggered cognitive deficits as evident by a significant (p<0.05) reduction in mean escape latency during acquisition trial and increased (p<0.05) time spent in target quadrant during probe trial in Morris water maze test, and reduction (p<0.05) in transfer latency in elevated plus maze test. Furthermore, both the doses of ellagic acid attenuated ICV colchicine induced rise in brain TBARS as well as TNF-α and simultaneously enhanced the GSH content.Ellagic acid prevented the brain of rodents from dementing effects of colchicine by attenuating the oxidative damage.


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Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole GM et al. (2000). Inflammation and Alzheimer’s disease. Neurobiology of Aging, 21(3), 383–421. http://dx.doi.org/10.1016/S0197-4580(00)00124-X

Ayala, A., Munoz, F. M., &Arguelles, S. (2014). Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine & Cellular Longevity, 360438. http://dx.doi.org/10.1155/2014/360438

Baddeley, A. D., Bressi, S., Della Sala, S., Logie, R., & Spinnler, H. (1991). The decline of working memory in Alzheimer’s disease. A longitudinal study. Brain, 114(Pt6), 2521–2542. http://dx.doi.org/10.1093/brain/114.6.2521

Bensimon, G., &Chermat, R. (1991). Microtubule disruption and cognitive defects: effect of colchicine on learning behavior in rats. Pharmacology Biochemistry Behavior, 38(1), 141–145. http://dx.doi.org/10.1016/0091-3057(91)90602-X

Braak, H., & Braak, E. (1995). Staging of Alzheimer’s disease related neurofibrillary changes. Neurobiology of Aging, 16(3), 271–278; discussion 278–284. http://dx.doi.org/10.1016/0197-4580(95)00021-6

Dhingra, D., & Chillar, R. (2012). Antidepressant-like activity of ellagic acid in unstressed and acute immobilization-induced stressed rat. Pharmacological Reports, 64, 796–807.

Dringen, R. (2000). Metabolism and functions of glutathione in brain. Progress in Neurobiology, 62(6), 649–671. http://dx.doi.org/10.1016/S0301-0082(99)00060-X

Ellman, G. L. (1959). Tissue sulfhydryl groups.Archives of Biochemistry & Biophysics, 82, 70–77.

Emerich, D. F., & Walsh, T. J. (1990). Cholinergic cell loss and cognitive impairments following intracerebroventricular or intradentate injection of colchicine. Brain Research, 517, 157–167. http://dx.doi.org/10.1016/0006-8993(90)91021-8

Fletcher, P. C., & Henson, R. N. (2001). Frontal lobes and human memory: insights from functional neuroimaging. Brain, 124(Pt 5), 849–881. http://dx.doi.org/10.1093/brain/124.5.849

Graham, W., & Roberts, J. B. (1953). Intravenous colchicine in the treatment of gouty arthritis. Annals of the Rheumatic Diseases, 12(1), 16–19.

Hartung, E. F. (1954). History of the use of colchicum and related medicaments in gout. Annals of the Reumatic Diseases, 13(3), 190–200.

Kumar, A., & Dogra, S. (2009). Neuroprotective effect of carvedilol, an adrenergic antagonist against colchicine induced cognitive impairment and oxidative damage in rat. Pharmacology Biochemistry Behavior, 92, 25-31. http://dx.doi.org/10.1016/j.pbb.2008.10.005

Kumar, A., Dogra, S., & Prakash, A. (2009). Neuroprotective effects of Centella asiatica against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress. International Journal of Alzheimer’s disease, 972178. http://dx.doi.org/10.4061/2009/972178

Kumar, A., Naidu, P. S., Sehgal, N., & Padi, S. S. V. (2007). Effect of curcumin on intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Journal of Medicinal Food, 10, 486–494. http://dx.doi.org/10.1089/jmf.2006.076

Kumar, A., Naidu, P. S., Sehgal, N., Padi, S. S. V., & Goyal, R. (2007). Colchicines induced neurotoxicity as an animal model of sporadic dementia of Alzheimer’s type. Pharmacological Reports, 59, 274–283.

Kumar, A., Dogra, S., & Prakash, A. (2010). Protective effect of naringin, a citrus flavonoid, against colchicine-induced cognitive dysfunction and oxidative damage in rats. Journal of Medicinal Food, 13(4), 976-984. http://dx.doi.org/10.1089/jmf.2009.1251

Kumar, M. H. V., & Gupta, Y. K. (2002). Intracerebroventricular administration of colchicine produces cognitive impairment associated with oxidative stress in rats. Pharmacology Biochemistry Behavior, 73, 565–571. http://dx.doi.org/10.1016/S0091-3057(02)00838-9

Landete, J. M. (2011). Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health.Food Research International, 44(5), 1150–1160. http://dx.doi.org/10.1016/j.foodres.2011.04.027

Larrosa, M., Garcia-Conesa, M. T., Espin, J. C., &Tomas-Barberan, F. A. (2010). Ellagitannins, ellagic acid and vascular health. Molecular Aspects of Medicine, 31(6), 513–539. http://dx.doi.org/10.1016/j.mam.2010.09.005

Levey, A. I., Hallanger, A. E., & Wainer, B. H. (1987). Cholinergic nucleus basalis neurons may influence the cortex via the thalamus. Neuroscience Letters, 74(1), 7–13. https://doi.org/10.1016/0304-3940(87)90042-5

Mandal, P. K., Saharan, S., Tripathi, M., & Murari, G. (2015). Brain glutathione levels-A novel biomarker for mild cognitive impairment and Alzheimer’s disease. Biological Psychiatry, 78(10), 702–710. http://dx.doi.org/10.1016/j.biopsych.2015.04.005

Marcus, D. L., Thomas, C., Rodriguez, C., Simberkoff, K., Tsai, J. S., Strafaci, J. A., & Freedman, M. L. (1998). Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease. Experimental Neurology, 150(1), 40–44. http://dx.doi.org/10.1006/exnr.1997.6750

Morris, R. (1984). Developments of a water-maze procedure for studying spatial learning in the rat. Journal of Neuroscience Methods, 11(1), 47–60.

Nakayama, T., &Sawada, T. (2002). Involvement of microtubule integrity in memory impairment caused by colchicine. Pharmacology Biochemistry Behavior, 71(1-2), 119–38. http://dx.doi.org/10.1016/S0091-3057(01)00634-7

Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Analytical Biochemistry, 95(2), 351–358.

O’Keefe, J., & Dostrovsky, J. (1971). The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Research, 34(1), 171–175.

Olmos, G., & Llado, J. (2014). Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity. Mediators of Inflammation, 861231. http://dx.doi.org/10.1155/2014/861231

Paxinos, G., Watson, C. R., & Emson, P. C. (1980). AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. Journal of Neuroscience Methods, 3, 129 -149.

Pierrot-Deseilligny, C., Muri, R. M., Rivaud-Pechoux, S., Gaymard, B., & Ploner, C. J. (2002). Cortical control of spatial memory in humans: the visuooculomotor model. Annals of Neurology, 52(1), 10–19. http://dx.doi.org/10.1002/ana.10273

Reitz, C., & Mayeux R. (2014). Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochemical Pharmacology, 88(4), 640–651. http://dx.doi.org/10.1016/j.bcp.2013.12.024

Ringheim, G. E., Szczepanik, A. M., Petko, W., Burgher, K. L., Zhu, S. Z., & Chao, C. C. (1998). Enhancement of beta-amyloid precursor protein transcription and expression by the soluble interleukin-6 receptor/interleukin-6 complex. Molecular Brain Research, 55(1), 35–44. http://dx.doi.org/10.1016/S0169-328X(97)00356-2

Sabuncu, M. R., Desikan, R. S., Sepulcre, J., Yeo, B. T., Liu, H., Schmansky, N. J., et al. (2011). The dynamics of cortical and hippocampal atrophy in Alzheimer disease. Archives of Neurology, 68(8), 1040–1048. http://dx.doi.org/10.1001/archneurol.2011.167

Shigematsu, K., & McGeer, P. L. (1992). Accumulation of amyloid precursor protein in neurons after intraventricular injection of colchicine. The American Journal of Pathology, 140(4), 787–794.

Sil, S., & Ghosh, T. (2016). Role of cox-2 mediated neuroinflammation on the neurodegeneration and cognitive impairments in colchicine induced rat model of Alzheimer’s Disease. Journal of Neuroimmunology, 291, 115–124. http://dx.doi.org/10.1016/j.jneuroim.2015.12.003

Sonkusare, S., Srinivasan, K., Kaul, C., & Ramarao, P. (2005). Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats.Life Sciences, 77, 1–14. http://dx.doi.org/10.1016/j.lfs.2004.10.036

Squire, L. R., & Zola, S. M. (1996). Structure and function of declarative and nondeclarative memory systems. Proceedings of the National Academy of Sciences USA, 93(24), 13515–13522.

Tan, Z. S., Beiser, A. S., Vasan, R. S., Roubenoff, R., Dinarello, C. A., Harris, T. B., et al. (2007). Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology, 68(22), 1902–1908.

Usta, C., Ozdemir, S., Schiariti, M., & Puddu, P. E. (2013). The pharmacological use of ellagic acid-rich pomegranate fruit. International Journal of Food Science & Nutrition, 64(7), 907–913. http://dx.doi.org/10.3109/09637486.2013.798268

Vorhees, C. V., & Williams, M. T. (2006). Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1(2), 848–858. http://dx.doi.org/10.1038/nprot.2006.116

Walsh, D. M., & Selkoe, D. J. (2004). Deciphering the molecular basis of memory failure in Alzheimer’s disease. Neuron, 44(1), 181–193. http://dx.doi.org/10.1016/j.neuron.2004.09.010

Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T., & DeLong, M. R. (1981). Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Annals of Neurology, 10(2), 122–126.

Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, A. W., Coyle, J. T., Delon, M. R. (1982). Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science, 215(4537), 1237–1239.




How to Cite

Jaspreet Kaur, Manish Kumar, & Nitin Bansal. (2016). Ellagic Acid Administration Reverses Colchicine- Induced Dementia in Rats. Journal of Pharmaceutical Technology, Research and Management, 4(1), 31–46. https://doi.org/10.15415/jptrm.2016.41003