Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions

	Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions
刊名	CHINESE JOURNAL OF NATURAL MEDICINES
	2016
卷号	14
关键词	MYCOPHENOLATE-MOFETIL GLYCYRRHETINIC ACID LIVER-MICROSOMES LICORICE PATHWAY PHARMACOKINETICS MEDICINE KAMPO HPLC 3A Diammonium glycyrrhizinate UDP-glucuronosyltransferase Sprague-Dawley rat Drug-drug interaction
ISSN号	2095-6975
其他题名	Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions
英文摘要	Glycyrrhizin is a major bioactive component of liquorice, which exerts multiple biochemical and pharmacological activities and is frequently used in combination with other drugs in the clinic. Mycophenolate mofetil (MMF), an immunosuppressant widely used in transplant patients, is metabolized by UDP-glucuronyltransferases (UGTs). Although significant evidence supports that glycyrrhizin could interact with the cytochrome P450s (CYPs), few studies have addressed its effects on UGTs. The present study aimed at investigating the regulatory effects of diammonium glycyrrhizinate (GLN) on UGTs in vitro and in vivo. We found that long-term administration of GLN in rats induced overall metabolism of MMF, which might be due to the induction of UGT1A protein expression. Hepatic UGT1A activity and UGT1A mRNA and protein expression were significantly increased in GLN-treated rats. UGT1A expression levels were also increased in the intestine, contradicting with the observed decrease in intestinal UGT1A activities. This phenomenon may be attributed to different concentrations of glycyrrhetinic acid (GA) in liver and intestine and the inhibitory effects of GA on UGT1A activity. In conclusion, our study revealed that GLN had multiple effects on the expression and activities of UGT1A isoforms, providing a basis for a better understanding of interactions between GLN and other drugs.
资助项目	[Key Lab of Drug Metabolism and Pharmacokinetics of Jiangsu Province]
语种	英语
CSCD记录号	CSCD:5755936
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/68540]
专题	中国科学院合肥物质科学研究院
推荐引用方式 GB/T 7714	. Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions[J]. CHINESE JOURNAL OF NATURAL MEDICINES,2016,14.
APA	(2016).Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions.CHINESE JOURNAL OF NATURAL MEDICINES,14.
MLA	"Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions".CHINESE JOURNAL OF NATURAL MEDICINES 14(2016).