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 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 microg), 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.
Datla
K P
KP
Department of Neuroinflammation, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Charing Cross Campus, Fulham Palace Road, London, UK.
Christidou
M
M
Widmer
W W
WW
Rooprai
H K
HK
Dexter
D T
DT
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D047309:Flavones; D005419:Flavonoids / Q000097:blood / Q000493:pharmacokinetics*; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000097:blood / Q000493:pharmacokinetics*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014781:Viscera / Q000187:drug effects / Q000378:metabolism
D047309:Flavones; D005419:Flavonoids; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C059006:tangeretin; D004298:Dopamine