Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions.
10.1016/S1875-5364(16)30063-2
- Author:
Fei-Yan LI
1
,
2
;
Hao XIE
3
;
Lin WENG
4
;
Hong WANG
3
;
Li-Juan CAO
3
;
Hai-Ping HAO
5
;
Guang-Ji WANG
6
Author Information
1. State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
2. Department of Good Clinical Practice, Zhejiang Cancer Hospital, Hangzhou 310022, China.
3. State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
4. Department of Good Clinical Practice, Zhejiang Cancer Hospital, Hangzhou 310022, China.
5. State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: hhp_770505@hotmail.com.
6. State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: guangjiwang@hotmail.com.
- Publication Type:Journal Article
- Keywords:
Diammonium glycyrrhizinate;
Drug-drug interaction;
Sprague-Dawley rat;
UDP-glucuronosyltransferase
- MeSH:
Animals;
Drugs, Chinese Herbal;
chemistry;
pharmacology;
Glucuronosyltransferase;
chemistry;
metabolism;
Glycyrrhizic Acid;
chemistry;
pharmacology;
Herb-Drug Interactions;
Intestines;
chemistry;
drug effects;
enzymology;
Kinetics;
Liver;
chemistry;
drug effects;
enzymology;
Male;
Rats;
Rats, Sprague-Dawley
- From:
Chinese Journal of Natural Medicines (English Ed.)
2016;14(7):534-540
- CountryChina
- Language:English
-
Abstract:
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.
