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Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease

Datla, Krishna P.1; Christidou, Maria1; Widmer, William W.2; Rooprai, Harcharan K.2; Dexter, David T.CA

Neuropharmacology And Neurotoxicology

Neuroprotective effects of a natural antioxidant tangeretin, a citrus flavonoid, were elucidated in the 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease (PD), after bioavailability studies. Following the chronic oral administration (10 mg/kg/day for 28 days), significant levels of tangeretin were detected in the hypothalamus, striatum and hippocampus (3.88, 2.36 and 2.00 ng/mg, respectively). The levels in the liver and plasma were 0.59 ng/mg and 0.11 ng/ml respectively. Unilateral infusion of the dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA; 8 μg), onto medial forebrain bundle significantly reduced the number of tyrosine hydroxylase positive (TH+) cells in the substantia nigra and decreased striatal dopamine content in the vehicle treated rats. Sub-chronic treatment of the rats with high doses of tangeretin (20 mg/kg/day for 4 days; p.o.) before 6-OHDA lesioning markedly reduced the loss of both TH+ cells and striatal dopamine content. These studies, for the first time, give evidence that tangeretin crosses the blood–brain barrier. The significant protection of striato-nigral integrity and functionality by tangeretin suggests its potential use as a neuroprotective agent.

Department of Neuroinflammation, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Charing Cross Campus, Fulham Palace Road, London W6 8RF; 1Experimental Neuro-Oncology Group, Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK; 2State of Florida, Department of Citrus, 700 Experiment Station Road, Lake Alfred, Florida, USA

CACorresponding Author

Received 19 September 2001; accepted 28 September 2001

© 2001 Lippincott Williams & Wilkins, Inc.