Dopamine transporter inhibitory and antiparkinsonian effect of common flowering quince extract.
Common flowering quince (FQ) is the fruit of Chaenomeles speciosa (Sweet) Nakai. FQ-containing cocktails have been applied to the treatment of neuralgia, migraine, and depression in traditional Chinese medicine. The present study assessed whether FQ is effective in dopamine transporter (DAT) regulation and antiparkinsonism by utilizing in vitro and in vivo assays, respectively. FQ at concentrations of 1-1000 microg/ml concentration-dependently inhibited dopamine uptake by Chinese hamster ovary (CHO) cells stably expressing DAT (D8 cells) and by synaptosomes. FQ had a slight inhibitory action on norepinephrine uptake by CHO cells expressing the norepinephrine transporter and no inhibitory effect on gamma-aminobutyric acid (GABA) uptake by CHO cells expressing GABA transporter-1 or serotonin uptake by the serotonin transporter. A viability assay showed that FQ mitigated 1-methyl-4-phenylpyridinium-induced toxicity in D8 cells. Furthermore, in behavioral studies, FQ alleviated rotational behavior in 6-hydroxydopamine-treated rats and improved deficits in endurance performance in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Furthermore, immunohistochemistry revealed that FQ markedly reduced the loss of tyrosine hydroxylase-positive neurons in the substantia nigra in MPTP-treated mice. In summary, FQ is a selective, potent DAT inhibitor and has antiparkinsonian-like effects that are mediated possibly by DAT suppression. FQ has the potential to be further developed for Parkinson's disease treatment.
Zhao
Gang
G
Cell Star Bio-Technologies Co., Limited, 898 Halei Road, Shanghai 201203, PR China.
Jiang
Zhi-Hua
ZH
Zheng
Xiang-Wei
XW
Zang
Shao-Yun
SY
Guo
Li-He
LH
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005116:Extrapyramidal Tracts / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D030781:Organisms, Genetically Modified; D010936:Plant Extracts / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D027824:Rosaceae / Q000737:chemistry*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D050485:GABA Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010936:Plant Extracts; D050486:Serotonin Plasma Membrane Transport Proteins; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine