Identification of metabolites of FR429, a potential antitumor ellagitannin, transformed by rat intestinal bacteria in vitro, based on liquid chromatography-ion trap-time of flight mass spectrometry analysis
Identification of metabolites of FR429, a potential antitumor ellagitannin, transformed by rat intestinal bacteria in vitro, based on liquid chromatography-ion trap-time of flight mass spectrometry analysis
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DOI：
10.1016/j.jpba.2012.07.028
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发表时间：
2012-12-01
影响因子：
3.4
通讯作者：
Du, Xiao-Wei
中科院分区：
文献类型：
--
作者：
Fu, Jie;Ma, Jing-Yi;Du, Xiao-Wei
FR429是从中国属贵州、云南苗族传统中草药头状何首乌中分离纯化出的一种具有潜在抗肿瘤活性的单宁。我们的初步药理研究结果表明，FR429具有抗肿瘤活性。然而，FR429的代谢尚未见报道。在这项研究中。采用LC-IT-TOF/MS联用技术对FR429在体外被肠道细菌生物转化后的不可预测代谢产物进行了表征。通过与母药MSN各阶段的准确分子质量和碎片离子的比较，共检测到13个代谢物，并对其中4个进行了核磁共振鉴定。结果表明，FR429在体外可被肠道细菌转化，主要通过水解和还原反应进行转化。为进一步研究FR429在体内的生物转化奠定了基础。(C)2012爱思唯尔B.V.保留所有权利。
FR429 is an ellagitannin with a potential antitumor activity, isolated and purified from Polygonum capitatum Buch.-Ham.ex D.Don, which is a traditional Miao-nationality herbal medicine in Guizhou and Yunnan of China. Our preliminary result of pharmacology study has indicated that the antitumor activity of FR429. However, the metabolism of FR429 has not been reported yet. In this study. LC-ion trap-time of flight mass spectrometry (LC-IT-TOF/MS) was used to characterize unpredictable metabolites of FR429 biotransformed by intestinal bacteria in vitro. Total thirteen metabolites were detected and characterized via comparisons of their accurate molecular masses and fragment ions of each MSn stage with those of the parent drug, and four of them were also elucidated by NMR. The results demonstrated that FR429 could be transformed by intestinal bacteria in vitro, mainly via hydrolysis and reduction reaction. This work provided a basis for the further study on the biotansformation of FR429 in vivo. (C) 2012 Elsevier B.V. All rights reserved.