Effect of silybin in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) induced parkinsonism in mice

Shajil Anand Justin, Senthil Gobalakrishnan, Sylvia Santhakumari Asirvatham


Background: Parkinson disease (PD) is a major neurological disorder known since ancient times. Though drugs are available for therapy, still effective drug targeting the etiopathogenesis is always going on.

Methods: After obtaining permission from animal ethics committee, the mice were divided into four groups of eight each (normal control, experimental control with normal diet only, silybin 300mg/kg, silybin 600mg/kg). At the end of 55 days the mice were subjected to overnight fasting followed by plasma and liver biochemical analysis.

Results: The mice treated with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) developed motor dysfunction and behavioural changes similar to PD, which was tested with rotarod test, photoactometer test and hang test which revealed the impaired performance, hypo-locomotion and impaired neuromuscular strength respectively. Treatment with silybin reversed the motor dysfunction significantly (p≤0.001) in a dose dependent manner. Biochemical analysis measured the oxidant (TBARS, SOD, CAT) and antioxidants (GPx and GSH) which revealed the oxidant activity of MPTP and antioxidant activity of silybin. Histopathological evaluation showed the cytoprotective effect of silybin.

Conclusions: Silybin by its antioxidant property has a neuroprotective activity both in motor activity and behaviourally in the MPTP induced Parkinson disease in mice. Hence present study offers a conclusive evidence that silybin is a neuroprotective. Diet supplemented with silybin can protect against neurodegenerative disorders and prevent the progression of neurodegeneration.


Antioxidant, Neuroprotective, Silybin

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Lang AE. Parkinsonism. In Goldman's Cecil Medicine. Eds Lee Goldman, Dennis Ausiello, 23rded. Saunders, Elsevier. New Delhi. 2007;433(2):2326-33.

Devi GM, Gururaj G, Satishchandra P. Neuroepidemiology in developing countries. Manual for descriptive studies. National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore. Publication No.33;1994.

Jankovic J. Parkinson's disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry. 2008;79(4):368-76.

Schott BH, Niehaus L, Wittmann BC, Schütze H, Seidenbecher CI, Heinze HJ, et al. Ageing and early-stage Parkinson's disease affect separable neural mechanisms of mesolimbic reward processing. Brain. 2007 Jul 11;130(9):2412-24.

Tom T, Cummings JL. Depression in Parkinson's disease. Pharmacological characteristics and treatment. Drugs Ageing. 1998;12(1):55-74.

Chen JJ, Nelson MV, Swope DM. Parkinson's disease. In Pharmacotherapy. A Pathophyiological Approach. Eds Joseph T. DiPiro, Barbara G. Wells, Cecily V. DiPiro, Terry L. Schwinghammer, 7th Ed. McGraw-Hill Book Co. Newyork, 2008;61:977-988.

Mahlon R, DeLong, Jorge L, Juncos. Parkinson’s disease and other extrapyramidal movement disorders. In Harrison’s Principles of Internal Medicine. Eds Fauci AS,Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, 17th Ed. McGraw-Hill Book Co. Newyork. 2008;366:2549-59.

Langston JW, Ballard P, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219:979-80.

Alper G, Girgin FK, Ozgönül M, Menteş G, Ersöz B. MAO inhibitors and oxidant stress in aging brain tissue. European neuropsycho pharmacology. 1999 Mar 1;9(3):247-52.

Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, et al. Parkinson disease in twins: an etiologic study. Jama. 1999 Jan 27;281(4):341-6.

Zheng W, Wang SY. Antioxidant activity and phenolic compounds in selected herbs. J. Agric. Food Chem. 2001;49(11):5165-70.

Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Archives of neurology. 2002 Oct 1;59(10):1541-50.

Ferger B, Spratt C, Teismann P, Seitz G, Kuschinsky K. Effects of cytisine on hydroxyl radicals in vitro and MPTP-induced dopamine depletion in vivo. European journal of pharmacology. 1998 Nov 6;360(2):155-63.

Muralikrishnan D, Mohanakumar KP. Neuroprotection by bromocriptine against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice. FASEB J. 1998;12:905-12.

Antolı́n I, Mayo JC, Sainz RM, del Brı́o MD, Herrera F, Martı́n V, et al. Protective effect of melatonin in a chronic experimental model of Parkinson’s disease. Brain research. 2002 Jul 12;943(2):163-73.

Fuller RW, Hemrick-Luecke SK. Deprenyl protection against striatal dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Res Comm Sub Abuse. 1984;5:241-6.

Kawasaki T, Ishihara K, Ago Y, Baba A, Matsuda T. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger, prevents 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced neurotoxicity in the substantia nigra but not the striatum. Journal of Pharmacology and Experimental Therapeutics. 2007 Jul 1;322(1):274-81.

Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs. 2001 Dec 1;61(14):2035-63.

Dixit N, Baboota S, Kohli K, Ahmad S, Ali J. Silymarin: A review of pharmacological aspects and bioavailability enhancement approaches. Indian journal of pharmacology. 2007 Jul 1;39(4):172.

Wang AL, Albert CH, Lau LT, Lee C, Tso MO. Minocycline inhibits LPS-induced retinal microglia activation. Neurochemistry international. 2005 Jul 31;47(1):152-8.

Smeyne RJ, Jackson-Lewis V. The MPTP model of Parkinson's disease. Brain Res Mol Brain Res. 2005;134(1):57-66.

Hamre K, Tharp R, Poon K, Xiong X, Smeyne RJ. Differential strain susceptibility following 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) administration acts in an autosomal dominant fashion: quantitative analysis in seven strains of Mus musculus. Brain research. 1999 May 15;828(1):91-103.

Carter CA, Pogribny M, Davidson A, Jackson CD, McGarrity LJ, Morris SM. Effects of retinoic acid on cell differentiation and reversion toward normal in human endometrial adenocarcinoma (RL95-2) cells. Anticancer research. 1996;16(1):17-24.

Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: The Cache County Study. Archives of neurology. 2004 Jan 1;61(1):82-8.

Meredith GE, Sonsalla PK, Cheselet. Animal models of Parkinson's disease progression. Acta Neuropathol. 2008;115:385-98.

Jackson-Lewis V, Jakowec M, Burke RE, Przedborski S. Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Neurodegeneration. 1995 Sep 30;4(3):257-69.

Perry TL, Godin DV, Hansen S. Parkinson’s disease: a disorder due to nigral glutathione deficiency?. Neuroscience Letters. 1982;33:305-10.

Singh RP, Dhanalakshmi S, Tyagi AK, Chan DC, Agarwal C, Agarwal R. Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels. Cancer research. 2002 Jun 1;62(11):3063-9.

He WX, Zhang S, Yang Q. Nutritional compositions of Silybum marianum gaertn seed oil and its hypolipidemic effect in rats. Acta Nutrimenta Sinica. 1996;18:163-7.

Tillerson JL, Michael Caudle W, Reverson ME. Detection of behavioural impairments correlated to neuro chemical deficits in mice treated with moderate doses of 1-methyi-4-phenyl-1,2,3,6-tetrahydropyridine. Exp Neuro. 2002;178:80-90.

Thaut MH, Miltner R, Lange HW, Hurt CP, Hoemberg V. Velocity modulation and rhythmic synchronization of gait in Huntington's disease. Movement Disorders. 1999 Sep 1;14(5):808-19.

Fernagut PO, Diguet E, Labattu B, Tison F. A simple method to measure stride length as an index of nigrostriatal dysfunction in mice. Journal of neuroscience methods. 2002 Jan 30;113(2):123-30.

Mohanasundari M, Srinivasan MS, Sethupathy S, Sabesan M. Enhanced neuroprotective effect by combination of bromocriptine and Hypericum perforatum extract against MPTP-induced neurotoxicity in mice. J of the Neu Sci. 2006 Nov 15;249(2):140-4.

Chen LJ, Gao YQ, Li XJ, Shen DH, Sun FY. Melatonin protects against MPTP/MPP+‐induced mitochondrial DNA oxidative damage in vivo and in vitro. Journal of pineal research. 2005 Aug 1;39(1):34-42.