Role of Ocimum sanctum in the experimental model of Alzheimer’s disease in rats
DOI:
https://doi.org/10.22377/ijgp.v3i1.49Abstract
Alzheimer’s disease (AD), a neurodegenerative disorder incapacitating elderly people towards the end of their life, accounts for approximately 70% of dementia. It affects 17-25 million elderly people worldwide. In spite of the remarkable increase in scientific knowledge about the pathobiology of AD, attempts other than modifying the cholinergic neurotransmission have proved futile. In Ayurveda a number of agents are in use, since ancient times, for chronic debilitating disorders. One such preparation, Ocimum sanctum (OS) has been found to possess anti-ulcerogenic, anti-inflammatory and neuroprotective activities. Because of the nonavailability of proper curative therapy for AD, the present study has been undertaken to evaluate the possible role of OS in experimental AD in rats.Experimental AD in rats was produced by a nucleus basalis magnacellularis lesion with ibotenic acid (IB) and intracerebroventricular (i.c.v) administration of colchicine (Col). Various behavioural tests and biochemical analysis were performed to explore the possible role of OS in AD. OS exhibited anxiolytic activity in an open field test. In an elevated plus maze test, OS significantly alleviated IB, and Col induced anxiety and depression in the Porsolt’s swim test. In Morris’ water maze test, OS pretreatments improved reference memory, working memory and spatial learning. Both IB and Col induced deficits in active avoidance learning and retention of learned
behaviour, which were significantly reversed by OS. IB and Col induced increased lipid peroxidase activity, which was significantly reversed by OS (as seen from the reductions in the malondialdehyde level) and stabilized the rise in superoxide dismutase activity, but it had no effect on the acetylcholinesterase activity. OS might be effective in clinical AD by virtue of its cognition enhancement, antidepressant and antianxiety properties, which are the primary needs to be addressed in AD.
Key words: Alzheimer’s disease, eugenol, Ocimum sanctum
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Parnetti L, Selin U, Mecocci P. Cognitive enhancement therapy
for Alzheimer’s disease: The way forward. Drugs 1997;53:752-68.
Geldmacher DS, Whitehouse Jr PJ. Differential diagnosis of
Alzheimer’s disease. Neurology 1997;48:S2-9.
Cummings JL, Mendez MF. Alzheimer’s disease: Cognitive and
behavioural pharmacotherapy. Conn Med 1997;61:543-52.
Max W. Drug treatments for Alzheimer’s disease: Shifting the
burden of care. CNS Drugs 1999;11:363-72.
Byrne GJ. Treatment of cognitive impairment in Alzheimer’s
disease. Aust J Hosp Pharm 1998;28:261-6.
Christie JE, Shering A, Ferguson J, Glen AI. Physostigmine and
arecoline: Effects of intravenous infusions in Alzheimer presenile
dementia. Br J Psychiatry 1981;138:46-50.
Little A, Levy R, Chuaqui-Kidd P, Hand D. A double blind, placebo
controlled trial of high dose lecithin in Alzheimer’s disease.
J Neurol Neurosurg Psychiatry 1985;48:736-42.
Jones RW, McCrone P, Guilhaume C. Cost effectiveness of
memantine in Alzheimer’s disease: An analysis based on a
probabilistic Markov model from a UK perspective. Drugs Aging
;21:607-20.
Francois C, Sintonen H, Sulkava R, Rive B. Cost effectiveness of
Memantine in moderately severe Alzheimer’s’ Disease: A Markov
model in Finland. Clin Drug Invest 2004;24:373-84.
Feldman H, Gauthier S, Hecker J, Vellas B, Hux M, Xu Y, et al.
Economic evaluation of donezepil in moderate to severe Alzheimer
disease. Neurology 2004;63:644-50.
Salloway S, Ferris S, Kluger A, Goldman R, Griesing T, Kumar D,
et al. Efficacy of donepezil in mild cognitive impairment:
A randomized placebo-controlled trial. Neurology 2004;63:651-7.
Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, et al.
Long-term donepezil treatment in 565 patients with Alzheimer’s
disease (AD2000): Randomized double-blind trial. Lancet
;363:2105-15.
Mantle D, Pickering AT, Perry E. Medical Plant extracts for
treatment of dementia: A review of their pharmacology, efficacy
and tolerability. CNS Drugs 2000;13:201-13.
Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA,
Mayeux R, et al. Effects of age, sex, and ethnicity on the association
between apolipoprotein E genotype and Alzheimer’s disease:
A meta-analysis. JAMA 1997;278:1349-56.
Stephenson J. Researchers find evidence of a new gene for lateonset
Alzheimer’s disease. JAMA 1997;277:775.
Gooch MD, Stennett DJ. Molecular basis of Alzheimer’s disease.
Am J Health System Pharm 1996;53:1545-57.
Paris D, Parker TA, Town T, Suo ZM, Fang CH, Humphrey J, et
al. Role of peroxynitrite in the vasoactive and cytotoxic effects of
Alzheimer’s β-amyloid (1 φ 40) peptide. Exp Neurol 1998;152:116-22.
Smith MA, Perry G, Richey PL, Sayre LM, Anderson VE, Beal MF,
et al. Oxidative damage in Alzheimer’s. Nature 1996;382:120-1.
Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, et al.
Assay for lipid peroxides in animal tissues by thiobarbituric acid
reaction. Anal Biochem 1979;95:351-8.
Frank B, Gupta S. A review of antioxidants and Alzheimer’s
disease. Ann Clin Psychiatry 2005;17:269-86.
Kennedy DO, Scholey AB. The psychopharmacology of European
herbs with cognition-enhancing properties. Curr Pharm Des
;12:4613-23.
Kritikar RR, Basu BD. Indian Medicinal Plants. In: Caius BJ,
Bhaskar KS, editors. Vol. 3, Dehradun, India: Bhishan Singh
Mahendra Paul Singh Co; 1935. p. 19-65.
Bhattacharya SK. In: Mukherjee B. Traditional Medicine. New
Delhi, India: IBH Publishing Co; 1993. p. 320.
Sharma PV. Dravyaguna Vijnan. Chaukhamba Sanskrit Sansthan,
Varanasi, India: 1978. p. 231.
Uma Devi P. Radioprotective, anticarcinogenic and antioxidant
properties of the Indian holy basil, Ocimum sanctum (Tulasi). Indian
J Exp Biol 2000;39:185-90.
Uma Devi P, Ganasoundari A, Vrinda B, Srinivasan KK,
Unnikrishnan MK. Radiation protection by Ocimum flavonoids
orientin and vicenin: Mechanism of action. Radiat Res 2000;154:
-60.
Geetha RK, Vasudevan DM. Inhibition of lipid peroxidation by
botanical extracts of Ocimum sanctum: In vivo and in vitro studies.
Life Sci 2004;76:21-8.
Subramanian M, Chintalwar GJ, Chattopadhyay S. Antioxidant and
radioprotective properties of an Ocimum sanctum polysaccharide.
Redox Rep 2005;10:257-64.
Kath RK, Gupta RK. Antioxidant activity of hydroalcoholic leaf
extract of Ocimum sanctum in animal models of peptic ulcer. Indian
J Physiol Pharmacol 2006;50:391-6.
Gupta S, Mediratta PK, Singh S, Sharma KK, Shukla R.
Antidiabetic, antihypercholesterolaemic and antioxidant effect of
Ocimum sanctum (Linn) seed oil. Indian J Exp Biol 2006;44:300-4.
Samson J, Sheeladevi R, Ravindran R. Oxidative stress in brain
and antioxidant activity of Ocimum sanctum in noise exposure.
Neurotoxicology 2007;28:679-85.
Hakkim FL, Shankar CG, Girija S. Chemical composition and
antioxidant property of holy basil (Ocimum sanctum L.) leaves,
stems, and inflorescence and there in vitro callus cultures. J Agric
Food Chem 2007;55:9109-17.
Sen P, Maiti PC, Puri S, Andulov NA, Valdman AV. Mechanism of
anti-stress activity of Ocimum sanctum Linn, eugenol, Tinospora
malabarica in experimental animals. Indian J Exp Biol 1992;30:
-6.
Sen P, Mediratta PK, Ray A. Effects of Azadirachta indica A Juss
on some biochemical, immunological and visceral parameters in
normal and stressed rats. Indian J Exp Biol 1992;30:1170-5.
Jyoti S, Satendra S, Sushma S, Anjana T, Shashi S. Antistressor
activity of Ocimum sanctum (Tulsi) against experimentally induced
oxidative stress in rabbits. Methods Find Exp Clin Pharmacol
;29:411-6.
Singh S, Majumdar DK, Rehan HM. Evaluation of anti-inflammatory
potential of Ocimum sanctum (Holy basil) and its possible mechanism
of action. J Ethnopharmacol 1996;54:19-26.
Devi PU, Ganasoundari A. Modulation of glutathione and
antioxidant enzymes by Ocimum sanctum and its role in protection
against radiation injury. Indian J Exp Biol 1999;37:262-8.
Prakash P, Gupta N. Therapeutic uses of Ocimum sanctum Linn
(Tulsi) with a note on eugenol and its pharmacological actions:
A short review. Indian J Physiol Pharmacol 2005;49:125-31.
Singh S, Taneja M, Majumdar DK. Biological activities of Ocimum
sanctum L. fixed oil: An overview. Indian J Exp Biol 2007;45:403-12.
Yanpallewar SU, Rai S, Kumar M, Acharya SB. Evaluation of
antioxidant and neuroprotective effect of Ocimum sanctum on
transient cerebral ischemia and long term cerebral hypoperfusion.
Pharmacol Biochem Behav 2004;79:155-64.
Yanpallewar, SU, Sunita Rai, Mohan Kumar, Satish Chauhan, SB,
Acharya. Neuroprotective effect of Azadiratcha indica on cerebral
post-ischemic reperfusion and hypoperfusion in rats. Life Sci
;76:1325-38.
Siddique YH, Ara G, Beg T, Afzal M. Anti-genotoxic effect of
Ocimum sanctum L. extract against cyproterone acetate induced
genotoxic damage in cultured mammalian cells. Acta Biol Hung
;58:397-409.
Manikandan P, Murugan RS, Abbas H, Abraham SK, Nagini S.
Ocimum sanctum Linn. (Holy Basil) ethanolic leaf extract protects
against 7,12-dimethylbenz(a)anthracene-induced genotoxicity,
oxidative stress, and imbalance in xenobiotic-metabolizing
enzymes. J Med Food 2007;10:495-502.
Jarrard LE. Selective hippocampal lesions and behaviour. In:
Isaacson RL and Pribram KH, The hippocampus, vol. 4. Plenum,
Publishing Corporation; 1986. p. 93-126.
Guide for the Care and Use of Laboratory Animals. NIH
Publication No. 85-23. Available from: http://grants.nih.gov/grants/
olaw/references/laba94.htm. [last revised on 1985].
Bhattacharya SK, Bhattacharya A, Das K, Muruganandam AV,
Sairam K. Further investigations on the antioxidant activity of
Ocimum sanctum using different paradigms of oxidative stress in
rats. J Nat Rem 2001;1:7-15.
Goel RK, Sairam K, Dorababu M, Prabha T, Rao Ch V. Effect of
standardized extract of Ocimum sanctum Linn. on gastric mucosal
offensive and defensive factors. Indian J Exp Biol 2005;43:715-21.
Pellow S, Chopin P, File SE, Briley M. Validation of open and closed
arm entries in an elevated plus maze as a measure of anxiety in
the rat. J Neurosci Methods 1985;14:149-67.
Willner P. The validity of animal models of depression.
Psychopharmacology (Berl) 1984;83:1-16.
Sherman AD, Petty F. Additivity of neurochemical changes
in learned helplessness and imipramine. Behav Neuro Biol
;35:344-53.
Pappas BA, De La Torre JC, Davidson CM, Keyes MT, Fortin T.
Chronic reduction of cerebral blood flow in the adult rat: Late
emerging CA1 cell loss and memory dysfunction. Brain Res
;708:50-8.
Kakkar P, Das B, Vishwanathan PN. A modified spectrophotometric
assay of superoxide dismutase. Indian J Biochem Biophys
;21:130-2.
Augustinson, KB. In methods of biochemical analysis. Vol. 5:
chapter 1, 1957. p. 43-47. 1
Brandeis, R, Pittel Z, Lachman, C, Heldman E, Luz S, Dachir S,
et al. AF64 induced cholinetoxicity: behavioural and biochemical
correlates. In: Fisher A, Hanin I, Lachman C, editors. Parkinson’s
and Alzheimer’s Disease: Strategies for Research and Development,
Plenum. New York: 1986. p. 469-78.
Lucki I. The forced swimming test as a model for core and
component behavioural effects of antidepressant drugs. Behav
Pharmacol 1997;8:523-32.
Bruce-Keller AJ, Begley JG, Fu, W, Butterfield DA, Bredesen DE,
Hutchins JB, et al. Bcl-2 protects isolated plasma and mitochondrial
membranes against lipid peroxidation induced by hydrogen
peroxide and amyloid beta-peptide. J Neurochem 1998;70:31-9.
Kelly JF, Furukawa K, Barger SW, Rengen MR, Mark RJ, Blanc EM,
et al. Amyloid β-peptide disrupts carbachol-induced muscarinic
cholinergic signal transduction in cortical neurons. Proc Natl Acad
Sci USA 1996;93:6753-8.
Eagger SA, Levy R, Sahakian BJ. Tacrine in Alzheimer’s disease.
Lancet 1991;337:989-92.
Davis KL, Mohs RC, Davis BM, Levy MI, Horvath TB, Rosenberg GS,
et al. Cholinergic treatment in Alzheimer’s disease: Implications
for future research. In: Corkin S, Davis KL, Crowdon JH, Usdin E,
Wurtman RJ, editors. Alzheimer’s disease: A report of progress in
research. New York: Raven Press; 1982. p. 483-94.
Mann DM. The locus coeruleus and its possible role in ageing and
degenerative disease of the human central nervous system. Mech
Ageing Dev 1983;23:73-94.
Palmer AM, Francis PT, Benton JS, Sims NR, Mann DM, Neary D,
et al. Presynaptic serotonergic dysfunction in patients with
Alzheimer’s disease. J Neurochem 1987;48:8-15.
Roberson MR, Harrell LE. Cholinergic activity and amyloid
precursor protein metabolism. Brain Res Brain Res Rev 1997;25:50-69.
