Improvement of Learning and Memory of Mice by Plumbagin

Abstract

Roots of Plumbago zeylanica have been reported to improve learning and memory of mice, but the effect of plumbagin on learning and memory of mice and the possible mechanisms for its effect on memory have not been explored till date. So the present study was designed to evaluate the effect of plumbagin on learning and memory of Swiss young male albino mice. Plumbagin (4, 8, 16 mg/kg, p.o.) and physostigmine (0.1 mg/kg,i.p.) per se were administered for 15 successive days to separate groups of mice. Behavioral parameters of learning and memory were recorded using Morris water maze. Acetylcholinesterase activity was estimated in brain of mice. Effect of plumbagin on scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.)-induced amnesia was also investigated. Locomotor activities of mice were also recorded. Plumbagin (8 and 16 mg/kg) and physostigmine significantly improved learning and memory of mice, as indicated by decrease in escape latency during training and increase in time spent in target quadrant of Morris water maze during retrieval. The drugs did not show any significant effect on locomotor activities of mice. Memory improving activity of plumbagin (16 mg/kg) was equivalent to physostigmine. Plumbagin significantly reversed scopolamine- and diazepam- induced amnesia in mice. Plumbagin and physostigmine also significantly reduced brain acetylcholinesterase activity of mice. In conclusion, plumbagin significantly improved memory of mice possibly through inhibition of brain acetylcholinesterase activity and through involvement of GABA-benzodiazepine pathway. Thus, plumbagin may be explored further for management of cognitive dysfunction.

  • Page Number : 147-159
  • Keywords
    Acetylcholinesterase, Learning, Memory, Morris water maze, Plumbagin
  • DOI Number
    10.15415/jptrm.2016.42010
  • Authors
    • D DhingraDepartment of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar -125 001 (Haryana), India
    • S ParshadDepartment of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar -125 001 (Haryana), India

References

  • Bartus, R.T., Dean, R.L., Beer, B., Lippa, A.S. (1982). The cholinergic hypothesis of geriatric memory dysfunction. Science, 217: 408–14. https://doi.org/10.1126/science.7046051
  • Bekker, A., Haile, M., Gingrich, K., Wenning, L., Gorny, A., Quartermain, D., Blanck, T. (2007). Physostigmine reverses cognitive dysfunction caused by moderate hypoxia in adult mice. Neurosurgical Anesthesiology, 105(3): 739–743. https://doi.org/10.1213/01.ane.0000265555.57472.49
  • Choi, S.Y., Son, T.G., Park, H.R., Jang, Y.J., Oh, S.B., Jin, B., Lee, J. (2012). Naphthazarin has a protective effect on the 1-Methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson’s disease model. Journal of Neuroscience Research, 90: 1842–1849. https://doi.org/10.1002/jnr.23061
  • Coyle, J.T., Price, D.L., DeLong, M.R. (1983). Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science, 219: 1184–1190. https://doi.org/10.1126/science.6338589
  • Dhingra, D., Bansal, S. (2015). Antidepressant-like activity of plumbagin in unstressed and stressed mice. Pharmacological Reports, 67(5): 1024-1032. https://doi.org/10.1016/j. pharep.2015.03.001
  • Dhingra, D., Parle, M., Kulkarni, S.K. (2004). Memory enhancing activity of Glycyrrhiza glabra in mice. Journal of Ethnopharmacolology, 91: 361–65. https://doi.org/10.1016/j.jep.2004.01.016
  • Dhingra, D., Joshi, P., Gupta, A., Chhillar, R. (2012). Possible involvement of monoaminergic neurotransmission in antidepressant-like activity of Emblica officinalis fruits in mice CNS. Neurosciences and Therapeutics, 18(5): 419–425. https://doi.org/10.1111/j.1755-5949.2011.00256.x
  • Deutsch, J.A., Rocklin, K.W. (1967). Amnesia induced by scopolamine and its temporal variations. Nature, 216: 89–90. https://doi.org/10.1038/216089b0
  • Domange, C., Schroeder, H., Violle, N., Peiffer, J., Canlet, C., Paris, A., Priymenko, N. (2013). Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse. Neurotoxicology, 38: 74–83. https://doi.org/10.1016/j.neuro.2013.06.005
  • Ellis, J.M. (2005). Cholinesterase inhibitors in the treatment of dementia. Journal of American Osteopathology Association, 1053: 145–158.
  • Ellman, G.L., Courtney, K.D., Andres, V. Jr., Feather-Stone, R.M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7: 88–95. https://doi.org/10.1016/0006-2952(61)90145-9
  • Filho, J.M.J.C., Birks, J. (2001). Physostigmine for dementia due to Alzheimer’s disease. Cochrane Database of Systematic Reviews, 2: 10. https://doi.org/10.1002/14651858.CD001499
  • Harburger, L.L., Bennett, J.C., Frick, K.M. (2007). Effects of estrogen and progesterone on spatial memory consolidation in aged females. Neurobiology Aging, 28: 602-10. https://doi.org/10.1016/j.neurobiolaging.2006.02.019
  • Hasselmo, M.E. (2006) The Role of Acetylcholine in Learning and Memory. Current Opinion in Neurobiology, 16: 710–715. https://doi.org/10.1016/j.conb.2006.09.002
  • Jensen, L.H., Stephens, D.N., Sarter, M., Petersen, E.N. (1987). Bidirectional effects of beta-carbolines and benzodiazepines on memory processes. Brain Research Bulletin 19:359–364. https://doi.org/10.1016/0361-9230(87)90104-3
  • Kalaria, R.N.,Maestre, G.E., Arizaga, R., Friedland, R.P., Galasko, D., et al.(2008). World Federation of Neurology Dementia Research Group. Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurolology, 7(9): 812–826. https://doi.org/10.1016/S1474-4422(08)70169-8.
  • Kavirajan, H., Schneider, L.S. (2007). Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurology, 69: 782–792. https://doi.org/10.1016/S1474-4422(07)70195-3
  • Kumar, H., More, S.V., Han, S.D., Choi, J.Y., Choi, D.K. (2012). Promising therapeutics with natural bioactive compounds for improving learning and memory — a review of randomized trials. Molecules, 17: 10503–10539. https://doi.org/10.3390/molecules170910503
  • Kumar, S., Gautam, S., Sharma, A. (2013). Antimutagenic and antioxidant properties of plumbagin and other naphthoquinones. Mutation Research, 755: 30–41. https://doi.org/10.1016/j.mrgentox.2013.05.007
  • Lou, P., Wong, F.Y., Ge, L., Zhang, F.Z., Liu, Y., Liang, L., et al., (2010). Anti-inflammatory and analgesic effect of plumbagin through inhibition of nuclear factor-beta activation. Journal of Pharmacology and Experimental Therapeutics, 335(3): 735–742. https://doi.org/10.1124/jpet.110.170852
  • Lu, S.H., Wu, J.W., Liu, H.L., Zhao, J.H., Liu, K.T., Chuang, C.K. et al., (2011) The discovery of potential acetylcholinesterase inhibitors: a combination of pharmacophore modeling, virtual screening, and molecular docking studies. Journal of Biomedical Sciences, 18: 8–20. https://doi.org/10.1186/1423-0127-18-8
  • Mohs, R.C., Davis, B.M., Johns, C.A., Mathe, A.A., Greenwald, B.S., et al. (1985). Oral physostigmine treatment of patients with Alzheimer’s disease. American Journal of Psychiatry, 1421: 28–33. https://doi.org/10.1176/ajp.142.1.28
  • Mittal, V., Sharma, S., Pawan, J.K., Anil, H.M.J. (2010). Plumbago zeylanica roots: A potential source for improvement of learning and memory. International Journal of Pharmacy and Bioallied Sciences, 6: 1-6.
  • Morris, R. (1984). Developments of a water-maze procedure for studying spatial learning in the rat. Journal of Neuroscience Methods, 11(1): 47-60. https://doi.org/10.1016/0165-0270(84)90007-4
  • Parle, M., Dhingra, D. (2003). Ascorbic Acid: a promising memory-enhancer in mice. Journal of Pharmacological Sciences, 93: 129-135. DOI: 10.1254/jphs.93.129
  • Parle, M., Singh, N. (2007). Reversal of memory deficits by atorvastatin and simvastatin in rats. Yakugaku Zasshi, 127: 1125-1137.
  • Pase, M.P., Kean, J., Sarris, J., Neale, C., Scholey, A.B., Stough, C. (2012). The cognitiveenhancing effects of Bacopamonnieri: a systematic review of randomized, controlled human clinical trials. Journal of Alternative and Complementary Medicine, 18(7): 647- 652. https://doi.org/10.1089/acm.2011.0367
  • Raskind, M.A., Peskind, E.R., Wessel, T., Yuan, W. (2000). Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology, 54(12): 2261-2268. https://doi.org/10.1212/WNL.55.5.744
  • Sharma, A.C., Kulkarni, S.K. (1992). Evaluation of learning and memory mechanisms employing elevated plus-maze in rats and mice. Progress in Neuropsychopharmacology and Biological Psychiatry, 16(1): 117-125. https://doi.org/10.1016/0278-5846(92)90014-6
  • Singh, N., Sharma, A., Singh, M. (1998). Possible mechanism of alprazolam-induced amnesia in mice. Pharmacology, 56: 46-50. https://doi.org/10.1159/000028181
  • Sivakumar, V., Prakash, R., Murali, M.R., Devaraj, H., Niranjali, D.S. (2005). In vivo micronucleus assay and GST activity in assessing genotoxicity of plumbagin in Swiss albino mice. Drug and Chemical Toxicology, 28(4): 499-507. https://doi.org/10.1080/01480540500263019
  • Son, T.G.,Camandola, S.,Arumugam, T.V., Cutler, R.G.,Telljohann, R.S., Mughal, M.R.,et al. (2010). Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia. Journal of Neurochemistry, 112(5): 1316-1326. https://doi.org/10.1111/j.1471-4159.2009.06552.x
  • Watanabe, T., Yamagata, N., Takasaki, K., Sano, K., Hayakawa, K., Katsurabayashi, S. et al. (2009). Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer’s disease. Brain Research 1249: 222-228. https://doi.org/10.1016/j.brainres.2008.10.029
  • Zhang, Z., Wang, X., Chen, Q., Shu, L., Wang, J., Shan, G. (2002). Clinical efficacy and safety of huperzine-alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial. Zhonghua Yi Xue Za Zhi, 82(14): 941-944.

  • Published Date : 2016-11-02