The Pycnogenol Improves Motor Function and Anxiety Behavior in 6-hydroaydoamine (6-OHDA)-induced Experimental Model of Parkinson’s Disease in NMRI Male Mice

Subject Areas : Journal of Animal Biology

Farajollah Jafari ¹ (Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran)
Mahdi Goudarzvand ² (Department of Physiology-Pharmacology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran, b: Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran)
Ramin Hajikhani ³ (Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran.)
Mostafa Qorbani ⁴ (Department of Epidemiology, Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran)
Jalal Solati ⁵ (Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Karaj Branch, Karaj, Iran)

Received: 2021-03-01 Accepted : 2021-05-27 Published : 2021-11-22

Keywords: Mice, catalepsy, anxiety, Parkinson’s Disease, Pycnogenol,

Abstract :

Considering the role of oxidants in the pathogenesis of this disease, in this study, the effect of pycnogenol as an antioxidant on the improvement of motor function and anxiety behavior in the experimental model of Parkinson’s disease were assessed. Forty male NMRI mice were randomly divided into five groups (n=8 in each group): The control (saline) unilaterally received 3 μl of normal saline solution containing 0.1% ascorbic acid, as a solvent of 6-hydroxy dopamine (6-OHDA), into the left strianum. The treatment group received 6-OHDA toxin containing 1% ascorbic acid at a rate of 3 µg/µl in the left striatum and then received the distilled water, as pycnogenol solvent, via gavage for 7 days (the lesion group). The pycnogenol-treated groups received pycnogenol at doses of 10, 20, and 30 mg/kg via gavage for 7 days. The animals were stereotaxically operated to inject 6-OHDA toxin into the left striatum. Seven days after induction of Parkinson’s model, apomorphine was intraperitoneally used at dose of 0.5 mg/kg and the number of rotation of the animals was measured to confirm the damage to neurons in the striatum. Besides, the catalepsy or muscle stiffness by the bar test and the anxiety behavior by the plus maze test (EPM) were measured. The total number of rotations in apomorphine test showed a significant decrease in the groups receiving pycnogenol. Moreover, administration of pycnogenol significantly reduced catalepsy in pycnogenol-treated groups. The result of the anxiety behavior test demonstrated that the percentage of open arm time (OAT) and the number of open and close arm entries, as an indicator of the animal’s locomotor activity, significantly increased in the pycnogenol-treated groups. Pycnogenol with its antioxidant effect ameliorates movement deficit and reduces anxiety behavior in animal model of Parkinson’s disease..

References:

1. Alvarez-Fischer D., Henze C., Strenzke C., Westrich J., Ferger B., Höglinger G., et al., 2008. Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type and α-synuclein-deleted mice. Experimental Neurology, 210(1): 182-193.


2. Bayeta E., Lau B.H., 2000. Pycnogenol inhibits generation of inflammatory mediators in macrophages. Nutrition Research, 20(2): 249-259.


3. Berry C., Vecchia C. L., Nicotera P., 2010. Paraquat and Parkinson's disease, Cell Death Differentiation, 17(7): 1115-1125.


4. Betarbet R., Sherer T.B., Greenamyre J.T., 2002. Animal models of Parkinson's disease. Bioassays, 24(4): 308-318.


5. Cesarone M.R., Belcaro G., Hosoi M., Ledda A., Feragalli B., Maione C., et al., 2020. Supplementary management with Pycnogenol® in Parkinson's disease to prevent cognitive impairment. Journal of Neurosurgical Sciences, 64(3): 258-262.


6. Chen W., Sun Z., Wang X.J., Jiang T., Huang Z, Fang D, et al., 2009. Direct interaction between Nrf2 and p21Cip1/WAF1 upregulates the Nrf2-mediated antioxidant response. Molecular Cell, 34(6): 663-673.


7. D'Andrea G., 2010. Pycnogenol: a blend of procyanidins with multifaceted therapeutic applications? Fitoterapia, 81(7): 724-736.


8. Durackova Z., Trebaticky B., Novotny V., Zitnanova I., Breza J., 2003. Lipid metabolism and erectile function improvement by pycnogenol®, extract from the bark of pinus pinaster in patients suffering from erectile dysfunction-a pilot study. Nutrition Research, 23(9): 1189-1198.


9. Eftekharzadeh B., Maghsoudi N., Khodagholi F., 2010. Stabilization of transcription factor Nrf2 by tBHQ prevents oxidative stress-induced amyloid β formation in NT2N neurons. Biochimie, 92(3): 245-253.


10. Franco R., Panayiotidis M.I., 2009. Environmental toxicity, oxidative stress, human disease and the" black box" of their synergism: how much have we revealed? Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 674(1-2): 1-2.


11. Fujita M., Nishino H., Kumazaki M., Shimada S., Tohyama M., Nishimura T., 1996. Expression of dopamine transporter mRNA and its binding site in fetal nigral cells transplanted into the striatum of 6-OHDA lesioned rat. Brain Research Molecular Brain Research, 39(1-2): 127-136.


12. Gao B., Chang C., Zhou J., Zhao T., Wang C., Li C., et al., 2015. Pycnogenol protects against rotenone-induced neurotoxicity in PC12 cells through regulating NF-κB-iNOS signaling pathway. DNA Cell Biology, 34(10): 643-649.


13. Gerlach M., Riederer P., 1996. Animal models of Parkinson's disease: an empirical comparison with the phenomenology of the disease in man. Journal of Neural Transmission, 103(8-9): 987-104.


14. Grimm T, Schäfer A., Högger P., 2004. JFRB, Medicine. Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (pycnogenol). Free Radical Biology and Medicine, 36(6): 811-822.


15. Hefti F., Melamed E., Sahakian B.J., Wurtman R.J., 1980. Circling behavior in rats with partial, unilateral nigro-striatal lesions: effect of amphetamine, apomorphine, and DOPA. Pharmacology Biochemistry and Behavior, 12(2): 185-188.


16. Kaplan M.H., 2013. STAT signaling in inflammation. JAK-STAT, 2(1): e24198.


17. Khan M.M., Kempuraj D., Thangavel R., Zaheer A., 2013. Protection of MPTP-induced neuroinflammation and neurodegeneration by Pycnogenol. Neurochemistry International, 62(4): 379-388.


18. Lin T.K., Liou C.W., Chen S.D., Chuang Y.C., Tiao M.M., Wang P.W., et al., 2009. Mitochondrial dysfunction and biogenesis in the pathogenesis of Parkinson’s disease. Chang Gung Medical Journal, 32(6): 589-599.


19. Mahmoudi J., Nayebi A.M., Samini M., Reyhani-Rad S., Babapour V., 2011. Buspirone improves the anti-cataleptic effect of levodopa in 6-hydroxydopamine-lesioned rats. Pharmacological reports, 63(4): 908-914.


20. Mei L., Mochizuki M., Hasegawa N., 2014. Pycnogenol ameliorates depression-like behavior in repeated corticosterone-induced depression mice model. Biomed Research International, 2014(3): 942927.


21. Peng Y.J., Lee C.H., Wang C.C., Salter D.M., Lee H.S., 2012. Pycnogenol attenuates the inflammatory and nitrosative stress on joint inflammation induced by urate crystals. Free Radical Biology and Medicine, 52(4): 765-774.


22. Pires J., Bonikovski V., Futuro-Neto H., 2005. Acute effects of selective serotonin reuptake inhibitors on neuroleptic-induced catalepsy in mice. Brazilian Journal of Medical and Biological Research, 38(12): 1867-1872.


23. Przedbroski S., Leviver M., Jiang H., Ferreira M., Jackson-Lewis V., Donaldson D., et al., 1995. Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by instrastriatal injection of 6-hydroxydopamine. Neuroscience, 67(3): 631-647.


24. Rascol O., Payoux P., Ory F., Ferreira J.J., Brefel‐Courbon C., Montastruc J.L., et al., 2003. Limitations of current Parkinson's disease therapy. Annals of Neurology, 53(3): 3-15.


25. Roghani M., Behzadi G., 2001. Neuroprotective effect of vitamin E on the early model of Parkinson’s disease in rat: behavioral and histochemical evidence. Brain Research, 892(1): 211-217.


26. Rohdewald P., 2002. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. International Journal of Clinical Pharmacology and Therapeutics, 40(4): 158-168.


27. Ryan J., Croft K., Mori T., Wesnes K., Spong J., Downey L., et al., 2008. An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. Journal of Psychopharmacology, 22(5): 553-562.


28. Stanislavov R., Nikolova V., 2003. Treatment of erectile dysfunction with pycnogenol and L-arginine. Journal of Sex and Marital Therapy, 29(3): 207-213.


29. Tabolacci C., Forni C., Jadeja R.N., Facchiano F., 2019. Natural compounds against cancer, inflammation, and oxidative stress. Biomed Research International, 2019: 9495628.


30. Tostes J., Medeiros P., Melo-Thomas L., 2013. Modulation of haloperidol-induced catalepsy in rats by GABAergic neural substrate in the inferior colliculus. Neuroscience, 255: 212-218.