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.
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 MS(n) 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.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China.
Jie
J
Fu
Jing-Yi
JY
Ma
Xian-Feng
XF
Zhang
Yan
Y
Wang
Ru
R
Feng
Yang-Chao
YC
Chen
Xiang-Shan
XS
Tan
Yi-Ying
YY
Zhang
Yu-Peng
YP
Sun
Ying
Y
Zhou
Chao
C
Ma
Chi-Yu
CY
He
Zhen-Xiong
ZX
Zhao
Xiao-Wei
XW
Du
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D001419:Bacteria / Q000378:metabolism*; D001711:Biotransformation; D002853:Chromatography, Liquid / Q000379:methods*; D005960:Glucosides / Q000737:chemistry* / Q000493:pharmacokinetics*; D029001:Herbal Medicine; D006868:Hydrolysis; D047348:Hydrolyzable Tannins / Q000737:chemistry* / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008516:Medicine, Chinese Traditional; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; C000595462:FR429 compound; D005960:Glucosides; D047348:Hydrolyzable Tannins; C013515:ellagitannin