Bakuchiol analogs inhibit monoamine transporters and regulate monoaminergic functions
文献类型：期刊论文
| 作者 | Zhao, G; Zang, SY; Zheng, XW; Zhang, XH; Guo, LH |
| 刊名 | BIOCHEMICAL PHARMACOLOGY
 |
| 出版日期 | 2008 |
| 卷号 | 75期号:9页码:1835-1847 |
| 关键词 | bakuchiol analogs monoamine transporter dopamine transporter norepinephrine transporter reuptake inhibitor |
| 通讯作者 | Guo, LH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,lhguo@sibs.ac.cn |
| 英文摘要 | Monoamine transporters play key roles in controlling monoamine levels and modulating monoamine reuptake. The objective of the present study was to identify monoamine transporter inhibitors from herbal sources. We discovered that bakuchiol analogs isolated from Fructus Psoraleae inhibited monoamine transporter uptake to differing degrees. The bakuchiol analog, Delta(3),2-hydroxybakuchiol was the most potent and efficacious reuptake blocker and was thus selected as the candidate target. Monoamine transporter inhibition by Delta(3),2-hydroxybakuchiol was more selective for the dopamine transporter (DAT) (IC50 = 0.58 +/- 0.1 mu M) and norepinephrine transporter (NET) (IC50 = 0.69 +/- 0.12 mu M) than for the serotonin transporter (SERT) (IC50 = 312.02 +/- 56.69 mu M). Delta(3),2-Hydroxybakuchiol exhibited greater potency (pEC(50) for DAT and NET) than bupropion and exhibited similar efficacy (E-max for DAT and/or NET) to bupropion and GBR12,935. Pharmacokinetically, Delta(3),2-hydroxybakuchiol competitively inhibited DAT and NET with partial reversibility and occupied cocaine binding sites. Moreover, Delta(3),2-hydroxybakuchiol counteracted 1-methyl-4-phenylpyridinium-induced toxicity in cells expressing DAT with similar efficacy to GBR12,935. In vivo studies showed that Delta(3),2-hydroxybakuchiol increased the activity of intact mice and improved the decreased activity of reserpinized mice. In the conditioned place preference test, preference scores in intact mice were unaffected by Delta(3),2-hydroxybakuchiol treatment. Bakuchiol analogs, especially Delta(3),2-hydroxybakuchiol, are monoamine transporter inhibitors involved in regulating dopaminergic and noradrenergic neurotransmission and may have represented potential pharmacotherapies for disorders such as Parkinson's disease, depression, and cocaine addiction. (C) 2008 Elsevier Inc. All rights reserved. |
| 学科主题 | Pharmacology & Pharmacy |
| 类目[WOS] | Pharmacology & Pharmacy |
| 关键词[WOS] | DOPAMINE TRANSPORTER ; NORADRENALINE TRANSPORTER ; PSORALEA-CORYLIFOLIA ; SUBSTANTIA-NIGRA ; IN-VITRO ; NEUROTRANSMITTER TRANSPORTERS ; PARKINSONS-DISEASE ; NUCLEUS-ACCUMBENS ; KNOCKOUT MICE ; RAT |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000255849400015 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1436]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhao, G,Zang, SY,Zheng, XW,et al. Bakuchiol analogs inhibit monoamine transporters and regulate monoaminergic functions[J]. BIOCHEMICAL PHARMACOLOGY,2008,75(9):1835-1847. |
| APA | Zhao, G,Zang, SY,Zheng, XW,Zhang, XH,&Guo, LH.(2008).Bakuchiol analogs inhibit monoamine transporters and regulate monoaminergic functions.BIOCHEMICAL PHARMACOLOGY,75(9),1835-1847. |
| MLA | Zhao, G,et al."Bakuchiol analogs inhibit monoamine transporters and regulate monoaminergic functions".BIOCHEMICAL PHARMACOLOGY 75.9(2008):1835-1847. |
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