Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] prevents 6-hydroxydopamine-induced dopamine depression in mouse striatum and increases superoxide scavenging activity in serum.
As superoxide (*O(2)-) and hydroxyl radical (*OH) have been implicated in pathogenesis of Parkinson's disease, free radical scavenging, antioxidant, and neuroprotective agents have attracted attention as ways to prevent progression. We examined effects of zingerone, an alkaloid extracted from ginger root, on 6-hydroxydopamine (6-OHDA)-induced dopamine (DA) reduction in mouse striatum. Zingerone administration 1 h before and for 6 more days following one intracerebroventricular 6-OHDA injection prevented reductions of striatal DA and its metabolites, and increased serum *O(2)- scavenging activity. Zingerone did not change activities of catalase or glutathione peroxidase in striatum or serum, or *O(2)- scavenging activity in striatum. Treatment with diethyldithiocarbamate, SOD inhibitor, abolished the protective effect of zingerone against 6-OHDA-induced DA reduction. In vitro, zingerone scavenged *O(2)- and *OH and suppressed lipid peroxidation only weakly. Thus, direct antioxidant effects may be a minor component of its putative neuroprotective effect; instead, zingerone acted mainly by increasing systemic superoxide dismutase activity. Effects of zingerone treatment in this model suggest possible value in treatment of Parkinson's disease.
Kabuto
Hideaki
H
Kagawa Prefectural College of Health Sciences, Japan. kabuto@chs.pref.kagawa.jp
Nishizawa
Masahiro
M
Tada
Mika
M
Higashio
Chie
C
Shishibori
Tsuyoshi
T
Kohno
Masahiro
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016627:Oxidopamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013481:Superoxides / Q000097:blood*; D013565:Sympatholytics / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D016166:Free Radical Scavengers; D009419:Nerve Tissue Proteins; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D013481:Superoxides; D017665:Hydroxyl Radical; C013738:zingerone; D006139:Guaiacol; D016627:Oxidopamine; D002374:Catalase; D005979:Glutathione Peroxidase; D004298:Dopamine; D006719:Homovanillic Acid