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.
Keywords: UPLC-QTOF-MS; central-icaritin (c-IT); icaritin (IT); isomers; metabolic profiling.
Copyright © 2014 John Wiley & Sons, Ltd.