British Journal of Nutrition

Molecular Nutrition

Chronic dietary supplementation with turmeric protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated neurotoxicity in vivo: implications for Parkinson's disease

Rajeswara Babu Mythria1, Jayagopalan Veenaa2 p1, G. Harisha1, B. S. Shankaranarayana Raoa2 and M. M. Srinivas Bharatha1 c1

a1 Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), PB No. 2900, Hosur Road, Bangalore 560 029, Karnataka, India

a2 Department of Neurophysiology, National Institute of Mental Health and Neurosciences, PB No. 2900, Hosur Road, Bangalore 560 029, Karnataka, India

Abstract

Multiple pathways including oxidative stress and mitochondrial damage are implicated in neurodegeneration during Parkinson's disease (PD). The current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Therefore, there is a demand for novel compound(s)/products that could target multiple pathways and protect the dying midbrain dopaminergic neurons, with potential utility as adjunctive therapy along with conventional drugs. Turmeric is a spice used in traditional Indian cuisine and medicine with antioxidant, anti-inflammatory and potential neuroprotective properties. To explore the neuroprotective property of turmeric in PD, mice were subjected to dietary supplementation with aqueous suspensions of turmeric for 3 months, mimicking its chronic consumption and challenged in vivo with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Brain samples from untreated and treated groups were characterised based on mitochondrial complex I (CI) activity, protein nitration and tyrosine hydroxylase immunoreactivity. Chronic turmeric supplementation induced the enzyme activity of γ-glutamyl cysteine ligase, which in turn increased glutathione levels and protected against peroxynitrite-mediated inhibition of brain CI. These mice were also protected against MPTP-mediated protein nitration, CI inhibition and degeneration of substantia nigra neurons in the brain. We conclude that chronic dietary consumption of turmeric protects the brain against neurotoxic insults, with potential application in neurodegeneration. Further characterisation of the active constituents of turmeric that potentially promote neuroprotection could improve the utility of dietary turmeric in brain function and disease.

(Received May 15 2010)

(Revised October 01 2010)

(Accepted December 14 2010)

(Online publication April 08 2011)

Correspondence:

c1 Corresponding author: Professor M. M. Srinivas Bharath, fax +91 80 26564830, email bharath@nimhans.kar.nic.in

p1 Present address: Laboratoire Psynugen, UMR INRA 1286, CNRS 5226, Université Bordeaux 2, Bâtiment UFR Pharmacie, 2ème Tranche, 2ème Etage, CC34, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33 076 Bordeaux Cedex, France.

Footnotes

Abbreviations: b.w., body weight; CI, mitochondrial complex I; γ-GCL, γ-glutamyl cysteine ligase; GSH, glutathione; MB, midbrain; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD, Parkinson's disease; PN, peroxynitrite; SN, substantia nigra; St, striatum; TH, tyrosine hydroxylase

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