title: Induction of CYP3A by morroniside in rats.
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.
authors.affiliation: Institute of Materia Medica, Shandong Academy of Medical Sciences, Ji'nan, Shandong 250062, China; Key Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Jinglai
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. Electronic address: zhangzhenqingpharm@163.com.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D029768:Cornus / Q000737:chemistry*; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008874:Midazolam / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D006027:Glycosides; D012333:RNA, Messenger; C488401:morroniside; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam
keywords: CYP3A; Induction; Morroniside; Rats