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学科主题: 物理化学
题名: In vitro Investigation of Glucuronidation of Magnolol: UGT2B7, a Major Responsible Isoform in HLMs
作者: Zhu LL(朱亮亮) ;  Liu HX(刘慧鑫) ;  Ge GB(葛广波) ;  Yang L(杨凌)
会议名称: 18th International Symposium on Microsomes and Drug Oxidations
会议日期: 2010-5-16
出版日期: 2010-05-16
会议地点: 中国
通讯作者: 杨凌
部门归属: 十八室
主办者: Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College
摘要: Background: Magnolol, a biphenyl phenol, is a major active component in Magnolia Officinalis (also known as the traditional Chinese Medicine Houpu), which is used to treat mental disturbance and gastrointestinal disorder. Recently magnolol has been drawn attentions for its various pharmacological activities including anti-microbial, anti-platelet aggregation, anti-oxidation, anti-anxiety, anti-depression and anti-cancer activities. Compared to its known pharmacological effects, the understanding of its metabolism is limited. Previous study in rat has shown that glucuronidation of magnolol was an important elimination pathway (Hattori et al., 1986). However, to date, littlie is known about its metabolic pathway in man. The objective of present study is to investigate Magnolol metabolic pathway and involving metabolic enzymes in man. Results: In this study, the formation of magnolol glucuronide was observed in the presence of human liver microsomes (HLMs) and recombinant human UGT isoforms including UGT1A1, 1A3, 1A9, 2B7 and extra hepatic isoforms 1A7, 1A8, 1A10. Our study showed that magnolol glucuronidation could occur at high efficiency in HLMs (with observed maximum velocity 7.05nmol/min/mg protein). Among UGT isoforms investigated, UGT2B7 showed the highest glucuronidation activity towards magnolol (with the maximum velocity 7.94±1.79 nmol/min/mg protein). Each UGT isoform mediated magnolol glucuronidation exhibited atypical kinetic behavior, among which UGT1A1, 1A3, 1A7, 2B7 show saturable inhibition kinetic and 1A9 shows biphasic kinetic. The HLMs mediated glucuronidation of magnolol had a strong correlation (r=0.93) with 3’-azido-3’deoxythymidine (AZT) glucuronidation, a probe reaction for UGT2B7. Diclofenac inhibited magnolol glucuronidation in HLMs with an IC50 value of 24.13μM, similarly to that in UGT2B7 with IC50 value of 23.35μM. Diclofenac showed weak inhibition activity towards UGT1A1, 1A3, 1A9 mediated magnolol glucuronidation with IC50 value >100μM. Conclusion: This study suggested that magnolol glucuronidation could occur at high efficiency in human liver with UGT2B7 as a major responsible isoform. References Hattori M, Endo Y, Takebe S, Kobashi K, Fukasaku N, Namba T. Metabolism of magnolol from Magnoliae cortex. II. Absorption, metabolism and excretion of [ring-14C] magnolol in rats. Chem Pharm Bull (Tokyo), 1986; 34(1): 158-167
语种: 中文
内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/114058
Appears in Collections:中国科学院大连化学物理研究所_会议论文

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Recommended Citation:
Zhu LL,Liu HX,Ge GB,et al. In vitro Investigation of Glucuronidation of Magnolol: UGT2B7, a Major Responsible Isoform in HLMs[C]. 见:18th International Symposium on Microsomes and Drug Oxidations. 中国. 2010-5-16.
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