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
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016-07-20 2016 |
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| Erschienen: |
2016-07-20 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2016 |
|---|---|
| Enthalten in: |
Zhongguo-tianran-yaowu - (2016), 07 vom: 20. Juli, Seite 534-540 Original Letters: Enthalten in (DE-576)307196259 (DE-576)307196259 |
| Reihe: |
China Academic Journals (CAJ), E, 医药卫生科技 = Medicine & Public Health |
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| Sprache: |
Chinesisch |
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| Weiterer Titel: |
Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP-Glucuronosyltransferases in rats: Implication in herb-drug interactions |
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| Beteiligte Personen: |
LI Fei-Yan [VerfasserIn] |
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| Links: |
oversea.cnki.net [lizenzpflichtig] |
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| Anmerkungen: |
Author info:LI Fei-Yan;XIE Hao;WENG Lin;WANG Hong;CAO Li-Juan;HAO Hai-Ping;WANG Guang-Ji;State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University;Department of Good Clinical Practice, Zhejiang Cancer Hospital |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
CAJ51241162X |
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| 520 | |a 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. | ||
| 610 | 2 | 4 | |a State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University |
| 610 | 2 | 4 | |a Department of Good Clinical Practice, Zhejiang Cancer Hospital |
| 650 | 4 | |a 中药学、方剂学 | |
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