Effects of Vitexin on the Pharmacokinetics and mRNA Expression of CYP Isozymes in Rats

被引:22
作者
Wang, Xin-shuai [1 ]
Hu, Xiao-chen [1 ]
Chen, Gui-ling [1 ]
Yuan, Xiang [1 ]
Yang, Rui-na [1 ]
Liang, Shuo [1 ]
Ren, Jing [1 ]
Sun, Jia-chun [1 ]
Kong, Guo-qiang [1 ]
Gao, She-gan [1 ]
Feng, Xiao-shan [1 ]
机构
[1] Henan Univ Sci & Technol, Dept Oncol, Inst Canc, Affiliated Hosp 1, Luoyang 471003, Henan, Peoples R China
关键词
vitexin; cocktail; CYP; mRNA; herb-drug interaction; TRADITIONAL CHINESE MEDICINES; DRUG-METABOLISM; CYTOCHROME-P450; ACTIVITY; LIVER-MICROSOMES; GRAPEFRUIT JUICE; HERBAL MEDICINES; PRESCRIBED DRUGS; IN-VIVO; ENZYMES; VALIDATION;
D O I
10.1002/ptr.5260
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In traditional therapy with Chinese medicine, vitexin has several pharmacological properties, including antinociceptive, antispasmodic, antioxidant, antimyeloperoxidase, and -glucosidase inhibitory activities. Recently, vitexin was shown to protect the heart against ischemia/reperfusion injury in an in vitro model by inhibiting apoptosis. The purpose of this study was to find out whether vitexin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied. A cocktail solution at a dose of 5mL/kg, which contained phenacetin (10mg/kg), tolbutamide (1mg/kg), and midazolam (5mg/kg), was given as oral administration to rats treated with short or long period of intravenous vitexin via the caudal vein. Blood samples were collected at a series of time points, and the concentrations of probe drugs in plasma were determined by HPLC-mass spectrometry (MS)/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time reverse transcription-polymerase chain reaction was performed to determine the effects of vitexin on the mRNA expression of CYP1A2, CYP2C11, and CYP3A1 in rat liver. Treatment with short or long period of vitexin had no effects on rat CYP1A2. However, CYP3A1 enzyme activity was inhibited by vitexin in a concentration-dependent and time-dependent manner. Furthermore, CYP2C11 enzyme activity was induced after short period treatment but inhibited after long period of vitexin treatment. The mRNA expression results were in accordance with the pharmacokinetic results. In conclusion, vitexin can either inhibit or induce activities of CYP2C11 and CYP3A1. Therefore, caution is needed when vitexin is co-administered with some CYP2C11 or CYP3A1 substrates in clinic, which may result in treatment failure and herb-drug interactions. Copyright (c) 2014 John Wiley & Sons, Ltd.
引用
收藏
页码:366 / 372
页数:7
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