Inhibitory Effect of Sauchinone on UDP-Glucuronosyltransferase (UGT) 2B7 Activity
| Autor: | Eun Chae Gong, Young Hee Choi, Byoung Hoon You |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
UGT1A6 Glucuronosyltransferase Pharmaceutical Science Dioxoles Pharmacology 030226 pharmacology & pharmacy Article Analytical Chemistry lcsh:QD241-441 Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine sauchinone lcsh:Organic chemistry Pharmacokinetics In vivo Saururus chinensis Drug Discovery Animals Humans Benzopyrans Drug Interactions Physical and Theoretical Chemistry UGT2B7 inhibition drug interaction biology Plant Extracts Chemistry Organic Chemistry Drug interaction Tracheophyta Uridine diphosphate Chemistry (miscellaneous) 030220 oncology & carcinogenesis Microsomes Liver biology.protein Microsome Thermodynamics Molecular Medicine Zidovudine |
| Zdroj: | Molecules; Volume 23; Issue 2; Pages: 366 Molecules, Vol 23, Iss 2, p 366 (2018) Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules23020366 |
| Popis: | Herb–drug interaction (HDI) limits clinical application of herbs and drugs, and inhibition of herbs towards uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has gained attention as one of the important reasons to cause HDIs. Sauchinone, an active lignan isolated from aerial parts of Saururus chinensis (Saururacease), possesses anti-oxidant, anti-inflammatory, and anti-viral activities. In pharmacokinetics of sauchinone, sauchinone is highly distributed to the liver, forming extensive metabolites of sauchinone via UGTs in the liver. Thus, we investigated whether sauchinone inhibited UGTs to explore potential of sauchinone–drug interactions. In human liver microsomes (HLMs), sauchinone inhibited activities of UGT1A1, 1A3, 1A6, and 2B7 with IC50 values of 8.83, 43.9, 0.758, and 0.279 μM, respectively. Sauchinone also noncompetitively inhibited UGT1A6 and 2B7 with Ki values of 1.08 and 0.524 μM, respectively. In in vivo interaction study using mice, sauchinone inhibited UGT2B7-mediated zidovudine metabolism, resulting in increased systemic exposure of zidovudine when sauchinone and zidovudine were co-administered together. Our results indicated that there is potential HDI between sauchinone and drugs undergoing UGT2B7-mediated metabolism, possibly contributing to the safe use of sauchinone and drug combinations. |
| Databáze: | OpenAIRE |
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