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Metabolic profiling of isomeric aglycones central‐icaritin ( c ‐IT) and icaritin (IT) in osteoporotic rats by UPLC‐QTOF‐MS
Author(s) -
Jiang Jun,
Feng Liang,
Sun E,
Li Haotian,
Cui Li,
Jia Xiaobin
Publication year - 2015
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.1672
Subject(s) - chemistry , glucuronidation , metabolic pathway , osteoporosis , ovariectomized rat , bone mineral , urine , metabolism , metabolic bone disease , high performance liquid chromatography , metabolite , pharmacology , excretion , chromatography , medicine , biochemistry , in vitro , microsome , hormone
The isomers, although of similarly chemical structures, have different pharmacological activities due to their metabolic processes in vivo . Central‐icaritin ( c ‐IT) and icaritin (IT) are isomers and major bioactive aglycones of the Herba Epimedii. In this study, we found that the anti‐osteoporotic effect of c ‐IT was stronger than IT on bone structural changes in osteoporotic rats evaluated by Micro‐μCT with the parameters of bone mineral density (BMD), bone mineral content (BMC), tissue mineral content (TMC), and tissue mineral density (TMD). c ‐IT treatment significantly increased the bone microarchitecture, compared with IT ( p < 0.05). In order to explain their differences in anti‐osteoporosis, the metabolic profiling and pathways of c ‐IT and IT in the plasma, bile, urine, and faeces of ovariectomized (OVX) rats were investigated by ultra‐performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC‐QTOF‐MS) after oral administration of c ‐IT or IT (80 mg/kg). Finally, 59 metabolites of c ‐IT and 43 metabolites of IT were identified by elucidating their corresponding quasimolecular ions and fragment ions. IT could be quickly absorbed into blood and reached a maximum plasma concentration, and then be rapidly conversed to its glucuronidation metabolites, most of which were excreted out by urine. Interestingly, the absorbed and conjugated speeds of c ‐IT were slower than IT. The metabolic processes of c ‐IT existed enterohepatic circulation, which decreased the metabolism and excretion rate of c ‐IT, and prolonged the anti‐osteoporosis effect. Our findings provided evidence on the difference on metabolic profiles of c ‐IT and IT in osteoporotic rats, which might shed new lights on improving anti‐osteoporotic effects of IT and c ‐IT. Copyright © 2014 John Wiley & Sons, Ltd.