Green tea polyphenol (–)‐epigallocatechin‐3‐gallate prevents N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced dopaminergic neurodegeneration

Abstract

In the present study we demonstrate neuroprotective property of green tea extract and (±)-epigallocatechin-3-gallate in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin caused dopamine neuron loss in substantia nigra concomitant with a depletion in striatal dopamine and tyrosine hydroxylase protein levels. Pretreatment of mice with either green tea extract (0.5 and 1 mg/kg) or (±)-epigallocatechin-3-gallate (2 and 10 mg/kg) prevented these effects. In addition, the neurotoxin caused an elevation in striatal antioxidant enzymes superoxide dismutase (240%) and catalase (165%) activities, both effects being prevented by (±)-epigallocatechin-3-gallate. (±)-Epigallocatechin-3-gallate itself also increased the activities of both enzymes in the brain. The neuroprotective effects are not likely to be caused by inhibition of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine conversion to its active metabolite 1-methyl-4-phenylpyridinium by monoamine oxidase-B, as both green tea and (±)-epigallocatechin-3-gallate are very poor inhibitors of this enzyme in vitro (770 mg/mL and 660 mM, respectively). Brain penetrating property of polyphenols, as well as their antioxidant and iron-chelating properties may make such compounds an important class of drugs to be developed for treatment of neurodegenerative diseases where oxidative stress has been implicated.

Antiparkinson drug – Mucuna pruriens shows antioxidant and metal chelating activity

“…Polyphenols cross the blood-brain barrier and can exert their antioxidant and ironchelating properties in the brain. Polyphenols such as (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration (Levites et al, 2001). In Parkinson's disease, glutathione is depleted in the nigrostriatal tract (Perry et al, 1982).…”

MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

“…Furthermore, the molecular mechanism by which EGCG affects Sema3 signaling requires further study. Interestingly, EGCG has neuroprotective and anti-inflammatory effects, however, the molecular substrates responsible for these effects are poorly understood (Koh et al, 2004;Lee et al, 2003;Levites et al, 2001;Mandel et al, 2004).…”

Role of tea catechins in prevention of aging and age-related disorders

“…This way, by maintaining mitochondrial integrity in nonrenewable cells like neurons, contributes to neuroprotection (Mandel et al, 2005). Studies have also reported that EGCG increases SOD and catalase activity in the striatum of rats (Levites et al, 2001) and preserves striatal dopamine levels (Choi et al, 2002). Overall, ECG and EGCG have been shown to possess more validity in cases of neurodegenerative diseases as compared to other catechins owing to their capacity to cross blood brain barriers (Suganuma et al, 1998).…”