NEUROPROTECTIVE EFFECT OF QUERCETIN IN NEUROTOXICITY INDUCED RATS: ROLE OF NEUROINFLAMMATION IN NEURODEGENERATION
Objective: The aim was to study the neuroprotective effect of quercetin in the animal model of neurodegeneration.
Materials and Methods: Quercetin (3,5,7,3',4'-pentahydroxy flavones) is a potential compound having both anti-inflammatory and anti-oxidant
properties with low gastric and cardiac side effect. Different Cyclooxygenase (COX-2) inhibitors such as nimesulide, refecoxib and celecoxib have
been proved to have their neuroprotective action in different animal models of neurodegenerative disorders, but they are burdened with high toxicity.
Different neurodegenerative models like haloperidol-induced catalepsy, reserpine induced vacuous chewing movements and 1-Methyl-4-phenyl-
1,2,3,6-tetrahydropyridine (MPTP) induced neurodegeneration were evaluated with levadopa at a dose of (30 mg/kg i.p.) and quercetin at a dose of
(25 mg/kg, p.o.) as standard and test drugs respectively.
Results: In the haloperidol-induced catalepsy model the increased cataleptic score was significantly reduced with both the standard drug levodopa
and the test drug quercetin. The increased frequencies of vacuous chewing movements on administration of reserpine were reversed with the
treatment of quercetin. The reduced actophotometer activity score due to reserpine was significantly reversed by quercetin. The decreased level of
lipid per-oxidation and increased glutathione concentration by the administration of quercetin that reversed the toxicity of MPTP.
Conclusion: Quercetin is a potential compound having both anti-inflammatory and anti-oxidant properties. These effects of enlights the
pharmacodynamic pathway of neuroprotective properties of quercetin in animal model study.
Keywords: Catalepsy, Cyclooxygenases, Neuroprotection, Quercetin.
Lee JM, Sancheti S, Noh CI, Cho DW, Choi JH. Ameliorative effect
of novel vitamin formula with herbal extracts on scopolamine-induced
Alzheimerâ€™s disease. Asian J Pharm Clin Res 2013;6(2):175-9.
Braak H, Del Tredici K, RÃ¼b U, de Vos RA, Jansen Steur EN, Braak E.
Staging of brain pathology related to sporadic Parkinsonâ€™s disease.
Neurobiol Aging 2003;24:197-211.
McGeer PL, McGeer EG. Inflammation and the degenerative diseases
of aging. Ann N Y Acad Sci 2004;1035:104-16.
McGeer PL, McGeer EG. NSAIDs and Alzheimer disease:
Epidemiological, animal model and clinical studies. Neurobiol Aging
Ahmad M, Zhang Y, Liu H, Rose ME, Graham SH. Prolonged
opportunity for neuroprotection in experimental stroke with selective
blockade of cyclooxygenase-2 activity. Brain Res 2009;1279:168-73.
Hyo JL, Hua L. Quercetin from Siegesbeckia glabrescens inhibits the
expression of COX-2 through the suppression of NF-kB activation in
microglia. Biomol Ther 2011;19:27-32.
Mayee R, Thosar R. Evalution of antiasthmatic activity of Calotropis
gigantea roots. Asian J Pharm Clin Res 2011;4(2):330-5.
Klemm WR. Evidence for a cholinergic role in haloperidol-induced
catalepsy. Psychopharmacology (Berl) 1985;85(2):139-42.
Naidu PS, Singh A, Kulkarni SK. Effect of Withania somnifera root
extract on reserpine-induced orofacial dyskinesia and cognitive
dysfunction. Phytother Res 2006;20(2):140-6.
Grimm JW, Kruzich PJ, See RE. Emergence of oral and locomotor
activity in chronic haloperidol-treated rats following cortical
N-methyl-D-aspartate stimulation. Pharmacol Biochem Behav
Wang T, Pei Z, Zhang W, Liu B, Langenbach R, Lee C, et al.
MPP+-induced COX-2 activation and subsequent dopaminergic
neurodegeneration. FASEB J 2005;19(9):1134-6.
Huong NT, Matsumoto K, Kasai R, Yamasaki K, Watanabe H. In vitro
antioxidant activity of Vietnamese ginseng saponin and its components.
Biol Pharm Bull 1998;21(9):978-81.
Chance B, Maehly AC. Assay catalases and peroxidise. Methods
Ellman G, Lysko H. A precise method for the determination of whole
blood and plasma sulfhydryl groups. Anal Biochem 1979;93(1):98-102.
Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF.
Expression of a mitogen-inducible cyclooxygenase in brain
neurons: regulation by synaptic activity and glucocorticoids. Neuron
Oka A, Takashima S. Induction of cyclo-oxygenase 2 in brains of
patients with Downâ€™s syndrome and dementia of Alzheimer type:
Specific localization in affected neurones and axons. Neuroreport
Pasinetti GM, Aisen PS. Cyclooxygenase-2 expression is increased
in frontal cortex of Alzheimerâ€™s disease brain. Neuroscience
Naidu PS, Singh A, Kulkarni SK. Carvedilol attenuates neurolepticinduced
orofacial dyskinesia: Possible antioxidant mechanisms. Br J
Teismann P, Ferger B. Inhibition of the cyclooxygenase isoenzymesCOX-1 and COX-2 provide neuroprotection in the MPTP-mouse model
of Parkinsonâ€™s disease. Synapse 2001;39(2):167-74.
Feng ZH, Wang TG, Li DD, Fung P, Wilson BC, Liu B, et al.
Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1,
, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in
the substantia nigra. Neurosci Lett 2002;329(3):354-8.
Figueiredo-Pereira ME, Li Z, Jansen M, Rockwell P. N-acetylcysteine
and celecoxib lessen cadmium cytotoxicity which is associated with
cyclooxygenase-2 up-regulation in mouse neuronal cells. J Biol Chem
Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S,
et al. Cyclooxygenase-2 is instrumental in Parkinsonâ€™s disease
neurodegeneration. Proc Natl Acad Sci U S A 2003;100(9):5473-8.
Sugama S, Yang L, Cho BP, DeGiorgio LA, Lorenzl S, Albers DS,
et al. Age-related microglial activation in 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration
in C57BL/6 mice. Brain Res 2003;964(2):288-94.
Mount MP, Lira A, Grimes D, Smith PD, Faucher S, Slack R, et al.
Involvement of interferon-gamma in microglial-mediated loss of
dopaminergic neurons. J Neurosci 2007;27(12):3328-37.
Lipton SA, Rosenberg PA. Excitatory amino acids as a final common
pathway for neurologic disorders. N Engl J Med 1994;330(9):613-22.
Kulkarni SK, Jain NK, Singh A. Cyclooxygenase isoenzymes and
newer therapeutic potential for selective COX-2 inhibitors. Methods
Find Exp Clin Pharmacol 2000;22(5):291-8.
Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: Structural,
cellular, and molecular biology. Annu Rev Biochem 2000;69:145-82.
Hurley SD, Oâ€™Banion MK, Song DD, Arana FS, Olschowka JA, Haber
SN. Microglial response is poorly correlated with neurodegeneration
following chronic, low-dose MPTP administration in monkeys. Exp
Morrow JD, Roberts LJ 2nd. Lipid-derived autocoids: Eicosanoids and
platelet activating factor. In: Hardman JG, Limbird LE, Gilman AG,
editors. Goodman & Gilmanâ€™s The Pharmcological Basis of Therapeutics.
th ed., Ch. 26. New York: McGraw-Hill; 2001. p. 669-87.
Abdel-Halim MS, LundÃ©n I, Cseh G, AnggÃ¥rd E. Prostaglandin profiles
in nervous tissue and blood vessels of the brain of various animals.
Neisewander JL, CastaÃ±eda E, Davis DA. Dose-dependent differences
in the development of reserpine-induced oral dyskinesia in rats:
Support for a model of tardive dyskinesia. Psychopharmacology (Berl)
Neisewander JL, CastaÃ±eda E, Davis DA, Elson HJ, Sussman AN.
Effects of amphetamine and 6-hydroxydopamine lesions on reserpineinduced
oral dyskinesia. Eur J Pharmacol 1996;305(1-3):13-21.
Nade VS, Dwivedi S, Kawale LA, Upasani CD, Yadav AV. Effect of
Hibiscus rosa sinensis on reserpine-induced neurobehavioral and
biochemical alterations in rats. Indian J Exp Biol 2009;47(7):559-63.
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