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Inhibitive effects of Fructus Psoraleae extract on dopamine transporter and noradrenaline transporter
Authors:Zhao Gang  Li Sheng  Qin Guo-Wei  Fei Jian  Guo Li-He
Affiliation:Cell Star Bio-Technologies Co., Limited, 1 Jury Road, Shanghai 201203, People's Republic of China.
Abstract:A petroleum ether extract (FP) from Fructus Psoraleae, seeds of Psoralea corylifolia L. (Leguminosae), was found to strongly inhibit dopamine (DA) uptake by dopamine transporter (DAT) heterogeneously expressed cells (D8 cells) and noradrenaline (NE) uptake by noradrenaline transporter (NET) heterogeneously expressed cells, which, however, had no effect on gamma-aminobutyric acid transporter heterogeneously expressed cells and serotonin transporter heterogeneously expressed cells at the concentration up to 100 microg/ml. These inhibitory effects were also confirmed by experiments on SK-N-SH cell line and synaptosomes from rats' brains. In addition, FP showed a significantly mitigating effect on 1-methyl-4-pyridinium induced injury of D8 cells. Meanwhile, FP dose-dependently reduced the binding of tritium-labeled cocaine analog (-)-2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane to DAT of D8 cells, which suggests that FP may inhibit DAT activity in the same way as cocaine does. Behavioral study showed FP had a long-lasting stimulant effects on the activity of intact mice and reserpinized mice. So FP is proposed as a kind of DAT and NET inhibitor and may be involved in the process of regulating the DA and NE system, and FP or its unknown bioactive compounds may be developed into new medicines for disorders such as Parkinson's disease, depression, Attention Deficit Hyperactivity Disorder (ADHD) or cocaine addiction.
Keywords:FPS, Fructus Psoraleae   Fw, Fe, FP, FPc, FPe and FPb, water-, ethanol-, petroleum ether-, chloroform-, acetic ester- and n-butanol-extract from Fructus Psoraleae, respectively   DA, dopamine   DAT, dopamine transporter   NE, noradrenaline   NET, noradrenaline transporter   SERT, serotonin transporter   MAO, monoaine oxydase   GBR12,935, 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine   GAT-1, γ-aminobutyric acid transporter   WIN35,428, (−)-2β-carbomethoxy-3β-(4-fluorophenyl) tropane   PD, Parkinson's disease   ADHD, Attention Deficit Hyperactivity Disorder   PBS, phosphate-buffered saline   HBSS, Hank's balanced salt solution   MPP+, 1-methyl-4-pyridinium   MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine   CHO, Chinese hamster ovary cells   i.p., intraperitoneal   SC, subcutaneous   CNS, central nervous system
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