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Characterization of the metabolism of sibiricaxanthone F and its aglycone in vitro by high performance liquid chromatography coupled with Q-trap mass spectrometry
Song, Yuelin; Yang, Xiaojuan; Jiang, Yong; Tu, Pengfei
关键词Sibiricaxanthone f Metabolism 1 Intestinal Bacteria 3 Liver Microsomes 6-trihydroxy-2 Lc-ms/ms 7-dimethoxyxanthone
刊名JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
2012-11-01
DOI10.1016/j.jpba.2012.06.038
70页:700-707
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Analytical ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]POLYGALA-TENUIFOLIA ROOT ; XANTHONE GLYCOSIDES ; MANGIFERIN ; GLUCURONIDATION ; DERIVATIVES ; RATS
英文摘要

To explain the low bioavailability of sibiricaxanthone F (SF) following oral administration and to predict its possible metabolites in vivo, the in vitro biotransformation of SF and its metabolic stability in intestinal bacteria (BI) were studied. The metabolism of SF and its aglycone (1,3,6-trihydroxy-2,7-dimethoxyxanthone, Xan) was characterized after incubation with human and rat liver microsomes (HLMs and RLMs). The chemical structures of the metabolites were tentatively identified on the basis of their mass profiles using high performance liquid chromatography coupled with an enhanced mass spectrometry-information dependent acquisition-enhanced product ion (EMS-IDA-EPI) scan mode on a hybrid triple quadrupole-linear ion trap mass spectrometer. The metabolic stability of SF in BI was determined using the multiple reaction monitoring (MRM) mode. As a result, five hydrolyzed metabolites (M1-M4 and Xan) were generated stepwise for SF when it was incubated with BI, whereas two demethylated products (M1 and M5) were detected for Xan in BI. The metabolic stability study of SF in BI revealed that the parent compound could be rapidly hydrolyzed by Bland that Xan, the main corresponding metabolite, increased rapidly. In RLMs and HLMs, two hydrolyzed metabolites (M2 and M3) mediated by CYP450 isoenzymes appeared for SF in the presence of an NADPH-regenerating system, whereas no metabolite was detected for Xan under the same conditions. One (M6) and three glucuronidated metabolites (M7-M9) were generated from SF and Xan, respectively, by phase II isoenzymes in liver microsomal proteins in the presence of uridine 5′-diphosphoglucuronic acid (UDPGA). Overall, the present study revealed that extensive first-pass elimination occurred for SF in intestinal bacteria and hepatic subcellular proteins in vitro, which could be one of the main reasons for the low bioavailability of SF; furthermore, the possible SF-related metabolites in rats and humans were elucidated to be mono-glucuronidated derivatives of Xan following oral administration of SF. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000309314600097
项目编号985-2-102-113 ; 30873429 ; 2012ZX09301002-002
资助机构Ministry of Education of China ; National Natural Science Foundation of China ; National Key Technology R&amp ; D Program "New Drug Innovation" of China
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52088
专题北京大学药学院
北京大学药学院_天然药物学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Song, Yuelin,Yang, Xiaojuan,Jiang, Yong,et al. Characterization of the metabolism of sibiricaxanthone F and its aglycone in vitro by high performance liquid chromatography coupled with Q-trap mass spectrometry[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2012,70:700-707.
APA Song, Yuelin,Yang, Xiaojuan,Jiang, Yong,&Tu, Pengfei.(2012).Characterization of the metabolism of sibiricaxanthone F and its aglycone in vitro by high performance liquid chromatography coupled with Q-trap mass spectrometry.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,70,700-707.
MLA Song, Yuelin,et al."Characterization of the metabolism of sibiricaxanthone F and its aglycone in vitro by high performance liquid chromatography coupled with Q-trap mass spectrometry".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 70(2012):700-707.
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