Effect of acute administration of hydroalcohol extract of Ilex paraguariensis St Hilaire (Aquifoliaceae) in animal models of Parkinson's disease

Ilex paraguariensis St Hilaire (Aquifoliaceae) is a plant widely cultivated in South America and with various reputed medicinal properties that can be attributed to phenolic constituents of the leaves: caffeine, theophylline and theobromine, besides the flavonoids, quercetin and rutin. This study examined the antiparkinsonian activity of the hydroalcohol extract of Ilex paraguariensis in models of protection against cerebral injury induced by MPTP and reversal of the catatonia induced by reserpine in mice. The hydroalcohol extract prevented MPTP‐induced hypolocomotion at doses of 250 and 500 mg/kg at the all time points observed and also prevented the reserpine‐induced catalepsy at the same doses. The extract potentiated the effect of apomorphine in preventing catatonia, suggesting a non‐dopaminergic activity, probably through antagonism of adenosine. In biochemical studies the hydroalcohol extract caused a significant decrease in the NO levels, exhibited a DPPH‐scavenging ability and was effective in preventing the oxidation of deoxyribose. The results obtained suggest that the hydroalcohol extract of Ilex paraguariensis may have an antiparkinsonian profile in animal models, probably through its antioxidant activity and antagonist action on adenosine A2A receptors. Copyright © 2007 John Wiley & Sons, Ltd.

[1]  B. Halliwell,et al.  Formation of a thiobarbituric‐acid‐reactive substance from deoxyribose in the presence of iron salts , 1981 .

[2]  P. Jenner,et al.  Adenosine A2A receptor antagonists as new agents for the treatment of Parkinson's disease. , 1997, Trends in pharmacological sciences.

[3]  P. Svenningsson,et al.  Distribution, biochemistry and function of striatal adenosine A2A receptors , 1999, Progress in Neurobiology.

[4]  R. Lamuela-Raventós,et al.  Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent , 1999 .

[5]  A. Gugliucci,et al.  Ilex paraguariensis extracts are potent inhibitors of nitrosative stress: a comparative study with green tea and wines using a protein nitration model and mammalian cell cytotoxicity. , 2005, Life sciences.

[6]  G. Schinella,et al.  Antioxidant effects of an aqueous extract of Ilex paraguariensis. , 2000, Biochemical and biophysical research communications.

[7]  J. Trojanowski,et al.  The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer's and Parkinson's diseases. , 2002, Free radical biology & medicine.

[8]  M. Schwarzschild,et al.  Neuroprotection by Caffeine and A2A Adenosine Receptor Inactivation in a Model of Parkinson's Disease , 2001, The Journal of Neuroscience.

[9]  E. Wang,et al.  Modelling the effects of age-related mtDNA mutation accumulation; complex I deficiency, superoxide and cell death. , 1995, Biochimica et biophysica acta.

[10]  C. Tanner,et al.  Association of coffee and caffeine intake with the risk of Parkinson disease. , 2000, JAMA.

[11]  Nizam Uddin Khan,et al.  Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. , 2003, Medical science monitor : international medical journal of experimental and clinical research.

[12]  D. Perl,et al.  Protein Nitration in Parkinson's Disease , 1998, Journal of neuropathology and experimental neurology.

[13]  J. Xie,et al.  Parkinson's Disease Brain Mitochondrial Complex I Has Oxidatively Damaged Subunits and Is Functionally Impaired and Misassembled , 2006, The Journal of Neuroscience.

[14]  Anthony H V Schapira,et al.  Etiology of Parkinson’s disease , 2006, Neurology.

[15]  Z. Deng,et al.  Separation procedures for naturally occurring antioxidant phytochemicals. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[16]  Koji Yamada,et al.  Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP , 1999, Psychopharmacology.

[17]  P. López,et al.  Phenolic compounds in seven South American Ilex species. , 2001, Fitoterapia.

[18]  B. Ferger,et al.  Neuroprotective effects of (±)‐kavain in the MPTP mouse model of Parkinson's disease , 2001, Synapse.

[19]  S. G. Leitão,et al.  Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method , 2001, Phytotherapy research : PTR.

[20]  M. Erion,et al.  The therapeutic potential of agents acting via purine receptors. , 1998, Expert opinion on investigational drugs.

[21]  P. Jenner,et al.  A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD , 2003, Neurology.

[22]  A. Gugliucci,et al.  Ilex paraguariensis extracts inhibit AGE formation more efficiently than green tea. , 2005, Fitoterapia.

[23]  C. Olanow,et al.  The pathogenesis of cell death in Parkinson's disease , 2006, Neurology.

[24]  B. Bartholomew A rapid method for the assay of nitrate in urine using the nitrate reductase enzyme of Escherichia coli. , 1984, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[25]  E. Vaudano,et al.  KW-6002 protects from MPTP induced dopaminergic toxicity in the mouse , 2005, Neuropharmacology.

[26]  M. Caporali,et al.  Akinesia due to catecholamine depletion in mice is prevented by caffeine. Further evidence for an involvement of adenosinergic system in the control of motility , 1991, The Journal of pharmacy and pharmacology.

[27]  E. Oztaş,et al.  Neuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson’s disease , 2003, Neurology.

[28]  P. Mazzafera Maté drinking: caffeine and phenolic acid intake , 1997 .

[29]  P. Riederer,et al.  Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man , 2005, Journal of Neural Transmission.

[30]  Richard J Smeyne,et al.  The MPTP model of Parkinson's disease. , 2005, Brain research. Molecular brain research.