PMID- 26869342
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1618-2650 (Electronic)
IS  - 1618-2642 (Linking)
VI  - 408
IP  - 10
DP  - 2016 Apr
TI  - Metabolites profiling of 10 bufadienolides in human liver microsomes and their 
      cytotoxicity variation in HepG2 cell.
PG  - 2485-95
LID - 10.1007/s00216-016-9345-y [doi]
AB  - Bufadienolides, a class of polyhydroxy steroids, exhibit significant antitumor 
      activity. In this study, a total of 39 metabolites from 10 bufadienolides were 
      detected and identified by ultrahigh-performance liquid chromatography (UHPLC) 
      coupled with an LTQ Orbitrap mass spectrometer. The results showed that 
      hydroxylation and dehydrogenation were the major metabolic pathways of 
      bufadienolides in human liver microsomes (HLMs). CYP3A4 was found to be the major 
      metabolic enzyme and CYP2D6 only mediated the dehydrogenation reaction. A 
      systematic validated cytotoxicity evaluation method for bufadienolide metabolites 
      at equal equivalents was established. Hellebrigenin (1), hellebrigenol (2), 
      arenobufagin (3), bufotalin (5), and bufalin (6) were selected to determine their 
      cytotoxicity against HepG2 cells before and after incubation in HLMs. All the 
      test samples were enriched by a validated solid-phase extraction (SPE) method. 
      Although the cytotoxicities of metabolites were weaker than those of the parent 
      compounds to different degrees, their effects were still strong.
FAU - Han, Lingyu
AU  - Han L
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China.
FAU - Wang, Hongjie
AU  - Wang H
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China.
FAU - Si, Nan
AU  - Si N
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China.
FAU - Ren, Wei
AU  - Ren W
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China.
FAU - Gao, Bo
AU  - Gao B
AD  - Anhui Jinchan Biochemistry Company Ltd., Huaibei, 235000, China.
FAU - Li, Yan
AU  - Li Y
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China.
FAU - Yang, Jian
AU  - Yang J
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China.
FAU - Xu, Miao
AU  - Xu M
AD  - State Intellectual Property Office of the P.R.C, Beijing, 100088, China.
FAU - Zhao, Haiyu
AU  - Zhao H
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China. hyzhao@icmm.ac.cn.
FAU - Bian, Baolin
AU  - Bian B
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, 100700, China. blbian@icmm.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160211
PL  - Germany
TA  - Anal Bioanal Chem
JT  - Analytical and bioanalytical chemistry
JID - 101134327
RN  - 0 (Bufanolides)
RN  - 29565-35-3 (bufadienolide)
SB  - IM
MH  - Bufanolides/*metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Hep G2 Cells
MH  - Humans
MH  - Microsomes, Liver/*metabolism
MH  - Tandem Mass Spectrometry
OTO - NOTNLM
OT  - Bufadienolides
OT  - CYP2D6
OT  - CYP3A4
OT  - HepG2 cell line
OT  - Metabolites
EDAT- 2016/02/13 06:00
MHDA- 2016/12/15 06:00
CRDT- 2016/02/13 06:00
PHST- 2015/11/10 00:00 [received]
PHST- 2016/01/18 00:00 [accepted]
PHST- 2016/01/06 00:00 [revised]
PHST- 2016/02/13 06:00 [entrez]
PHST- 2016/02/13 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1007/s00216-016-9345-y [pii]
AID - 10.1007/s00216-016-9345-y [doi]
PST - ppublish
SO  - Anal Bioanal Chem. 2016 Apr;408(10):2485-95. doi: 10.1007/s00216-016-9345-y. Epub 
      2016 Feb 11.