QQ客服 官方微博 反馈留言

	Characterization of human metabolic pathway of daphnetin: UDP-glucuronosyltransferase involved in the methylated daphnetin
	Liang SC(梁思成) ; Ge GB(葛广波) ; Liu HX(刘慧鑫) ; Zhang JW(张江伟) ; Yang L(杨凌)
	2009-10-18
会议名称	16th north american regional issx meeting
会议日期	2009-10-18
会议地点	美国
页码	286/1
通讯作者	杨凌
中文摘要	daphnetin (7, 8-dihydroxycoumarin) was used for treatment against coagulation disorders and burger’s since 1980s. like other coumarin analogs, daphnetin has been found to exhibit broad biological effects including anti-inflammatory, antimicrobial, anti-malarial, anti-cancer activities. previous studies indicated that daphnetin was metabolized rapidly in vivo. however its metabolic pathway in human is still unknown. according to the structure of daphnetin, there are two phenolic hydroxyl groups in the coumarin skeleton, indicating the potential phase ii enzymes mediated clearance. our previous study revealed that the ugt1a9 and ugt1a6 involved in the glucuronidation of daphnetin. in this study, we investigated other phase ii metabolic pathway of daphnetin. one metabolite (m-1) was detected when daphnetin was incubated with human liver s9 in the presence of 3’-phosphoadenosine 5’-phosphosulfate, indicating the existence of methylation pathway of daphnetin by catechol-o-methyltransferase (comt). m-1 was indentified as the c-7 methylated daphnetin by liquid chromatography/mass spectrometry (lc/ms) and nuclear magnetic resonance (nmr). notably, m-1 was found can be glucuronidated in human liver microsomes (hlms) in the presence of udpga. further study showed that ugt1a1, ugt1a3, ugt1a7, ugt1a8, ugt1a9 and ugt1a10 involved in m-1 glucuronidation by using 12 commercially available recombinant human ugts. these results indicated that daphnetin can be metabolized by comt and the methylated metabolite (m-1) can be further metabolized by several ugts, which revealed that the phase ii metabolic pathway plays a crucial role in metabolic clearance of daphnetin.
会议主办者	the international society for the study of xenobiotics (issx)
学科主题	物理化学
语种	中文
WOS记录号	WOS:000280165300273
内容类型	会议论文
源URL	[http://159.226.238.44/handle/321008/113672]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
推荐引用方式 GB/T 7714	Liang SC,Ge GB,Liu HX,et al. Characterization of human metabolic pathway of daphnetin: UDP-glucuronosyltransferase involved in the methylated daphnetin[C]. 见:16th north american regional issx meeting. 美国. 2009-10-18.

个性服务

查看访问统计

相关权益政策

暂无数据

收藏/分享

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。