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Short-Term Supplementation with Plant Extracts Rich in Flavonoids Protect Nigrostriatal Dopaminergic Neurons in a Rat Model of Parkinson's Disease

Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College, Charing Cross Campus (K.P.D., V.Z., D.R., S.P., D.D.)
The Food Research Centre, Department of Applied Science, London South Bank University (O.I.A.), London, UNITED KINGDOM
Meiji Seika Kaisha Limited, Food and Health R & D Laboratories (N.O.), Saitama, JAPAN
Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University (O.I.A.), Seoul, KOREA

Address reprint requests to: Dr. David T. Dexter, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College, Charing Cross Campus, St. Dunstan's Road, London W6 8RP, UNITED KINGDOM. E-mail: d.dexter{at}imperial.ac.uk

Objective: Antioxidants from plants were known to reduce the oxidative stress by scavenging free radicals, chelating metal ions and reducing inflammation. As increased oxidative stress was implicated in the nigrostriatal dopaminergic neuronal loss in Parkinson's disease (PD), we have assessed whether the plant extracts protects the nigrostriatal dopaminergic neurons in the animal model of PD.

Methods: Male adult Sprague-Dawley rats were treated orally between 10am–11am each day with the extracts from tangerine peel, grape seeds, cocoa and red clover for four days. One hour after the final dosing, the left medial forebrain bundle was lesioned by infusing the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA; 12µg) under anaesthesia. Seven days post-lesion, the number of dopaminergic cells in the substantia nigra pars compacta and the levels of dopamine and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striata were quantified and compared with the vehicle-treated groups.

Results: Compared to the unlesioned side, 6-OHDA lesions significantly reduced the number of dopaminergic cells and the levels of dopamine and its metabolites DOPAC and HVA in the vehicle-treated animals. Pretreatment of animals with extracts of tangerine peel (rich in polymethoxylated flavones; 35 mg/kg/day), cocoa-2 (rich in procyanidins; 100 mg/kg/day) and red clover (rich in isoflavones; 200 mg/kg/day) significantly attenuated the 6-OHDA-induced dopaminergic loss. However, no significant protection was seen in animals supplemented with red and white grape seeds (rich in catechins; 100 mg/kg/day), and cocoa-1 (rich in catechins; 100 mg/kg/day).

Conclusions: Pre-treatment of plant extracts rich in polymethoxylated flavones, procyanidins and isoflavones but not catechins protected the nigrostriatal dopaminergic neurons in the rat model of PD.

Key words: ntioxidants, flavonoids, 6-hydroxydopamine, neuroprotection, Parkinson's disease