A novel compound N-1, N-5-(Z)-N-10-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition

	A novel compound N-1, N-5-(Z)-N-10-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition
	Zhao, G; Gai, Y; Chu, WJ; Qin, GW; Guo, LH
刊名	EUROPEAN NEUROPSYCHOPHARMACOLOGY
	2009
卷号	19 期号:10 页码:749-758
关键词	Safflower N-1 Serotonin transporter Reuptake Inhibitor N-5-(Z)-N-10-(E)-tri-p-coumaroylspermidine
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	Safflower, the dry flower of Carthamus tinctorius L., has long been applied for empirically treating cerebral ischemia and depression in traditional Chinese medicine. Pathogenesis of major depression involves monoaminergic transmission. The present study assessed whether safflower or its isolate would be effective in functionally regulating monoamine transporter using in vitro screening cell lines. We discovered that safflower insoluble fraction significantly inhibited serotonin uptake in Chinese hamster ovary cells stably expressing serotonin transporter (i.e. S6 cells). This fraction went through an activity-guided isolation and an active ingredient was obtained, which was subsequently elucidated as a novel coumaroylspermidine analog N-1,N-5-(Z)-N-10-(E)-tri-p-coumaroylspermidine using NMR techniques. Pharmacologically, this compound potently and selectively inhibited serotonin uptake in S6 cells or in synaptosomes, with IC50 of 0.74 +/- 0.15 mu M for S6 cells or 1.07 +/- 0.23 mu M for synaptosomes and with a reversible competitive property for the 5HT-uptake inhibition. The potency of it for 5HT uptake was weaker than that of fluoxetine whereas efficacy generally similar for both. Animals treated with this testing compound showed a significant decrease in synaptosomal 5HT uptake capacity. Thus, N-1,N-5-(Z)N-10-(E)-tri-p-coumaroylspermidine is a novel serotonin transporter inhibitor, which could improve neuropsychological disorders through regulating serotoninergic transmission. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.
学科主题	Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
类目[WOS]	Clinical Neurology ; Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]	HYDROXYSAFFLOR-YELLOW ; DOPAMINE TRANSPORTER ; MONOAMINE TRANSPORTERS ; LINOLENIC ACID ; RAT-BRAIN ; OIL CAKE ; IN-VITRO ; SAFFLOWER ; DERIVATIVES ; ANXIETY
收录类别	SCI
语种	英语
WOS记录号	WOS:000270312300009
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1249]
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,Gai, Y,Chu, WJ,et al. A novel compound N-1, N-5-(Z)-N-10-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition[J]. EUROPEAN NEUROPSYCHOPHARMACOLOGY,2009,19(10):749-758.
APA	Zhao, G,Gai, Y,Chu, WJ,Qin, GW,&Guo, LH.(2009).A novel compound N-1, N-5-(Z)-N-10-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition.EUROPEAN NEUROPSYCHOPHARMACOLOGY,19(10),749-758.
MLA	Zhao, G,et al."A novel compound N-1, N-5-(Z)-N-10-(E)-tri-p-coumaroylspermidine isolated from Carthamus tinctorius L. and acting by serotonin transporter inhibition".EUROPEAN NEUROPSYCHOPHARMACOLOGY 19.10(2009):749-758.