Abstract
Morroniside is one of the most important iridoid glycosides in the herbal drug Cornus officinalis Sieb. et Zucc. The current study was designed to investigate the ex vivo and in vivo effects of morroniside on CYP3A activity in rats after treatment with morroniside for 7 days (at 10, 30, 90 mg/kg, i.g.). Morroniside was found to induce CYP3A. According to the ex vivo experiment, the activity of CYP3A was measured by the quantification of 1-hydroxymidazolam, which was the metabolite from CYP3A probe substrate, midazolam. The concentration of 1-hydroxymidazolam was determined by using a validated liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) method. The levels of messenger RNA (mRNA) and protein of CYP3A were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting analysis, respectively. The pharmacokinetics of midazolam in rats after treatment with morroniside for 7 days (at 10, 30, 90 mg/kg, i.g.) were investigated in vivo. After treatment with morroniside, the activity, mRNA and protein expression of CYP3A were significantly induced and the absorbance and bioavailability of midazolam in rats were reduced. The results indicated that morroniside could induce the activity of CYP3A.
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