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

Neuroprotective effects of a natural antioxidant tangeretin, a citrus flavo noid, were elucidated in the 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease (PD), after bioavailability studies. Following the chr onic oral administration (10 mg/kg/day for 28 days), significant levels of tangeretin were detected in the hypothalamus, striatum and hippocampus (3.8 8, 2.36 and 2.00 ng/mg, respectively). The levels in the liver and plasma w ere 0.59 ng/mg and 0.11 ng/ml respectively. Unilateral infusion of the dopa minergic neurotoxin, 6-hydroxydopamine (6-OHDA; 8 mug), onto medial forebra in bundle significantly reduced the number of tyrosine hydroxylase positive (TH+) cells in the substantia nigra and decreased striatal dopamine conten t 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 t he blood-brain barrier. The significant protection of striato-nigral integr ity and functionality by tangeretin suggests its potential use as a neuropr otective agent. NeuroReport 12:3871-3875 2001 Lippincott Williams & Wilkins .