Tetrahydrofurofuranoid Lignans, Eudesmin, Fargesin, Epimagnolin A, Magnolin, and Yangambin Inhibit UDP-Glucuronosyltransferase 1A1 and 1A3 Activities in Human Liver Microsomes
| العنوان: | Tetrahydrofurofuranoid Lignans, Eudesmin, Fargesin, Epimagnolin A, Magnolin, and Yangambin Inhibit UDP-Glucuronosyltransferase 1A1 and 1A3 Activities in Human Liver Microsomes |
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| المؤلفون: | Hye Suk Lee, Im-Sook Song, Eun Jeong Park, Ria Park, Han Chang Kang, Joo Young Lee, Yong-Yeon Cho |
| المصدر: | Pharmaceutics Volume 13 Issue 2 Pharmaceutics, Vol 13, Iss 187, p 187 (2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | UGT1A4, fargesin, Glucuronidation, lcsh:RS1-441, Pharmaceutical Science, yangambin, Pharmacology, 030226 pharmacology & pharmacy, Article, human liver microsomes, lcsh:Pharmacy and materia medica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, eudesmin, In vivo, Chenodeoxycholic acid, magnolin, Uridine, In vitro, UGT2B7, epimagnolin A, chemistry, 030220 oncology & carcinogenesis, Microsome, UDP-glucuronosyltransferase |
| الوصف: | Eudesmin, fargesin, epimagnolin A, magnolin, and yangambin are tetrahydrofurofuranoid lignans with various pharmacological activities found in Magnoliae Flos. The inhibition potencies of eudesmin, fargesin, epimagnolin A, magnolin, and yangambin on six major human uridine 5′-diphospho-glucuronosyltransferase (UGT) activities in human liver microsomes were evaluated using liquid chromatography–tandem mass spectrometry and cocktail substrates. Eudesmin, fargesin, epimagnolin A, magnolin, and yangambin inhibited UGT1A1 and UGT1A3 activities, but showed negligible inhibition of UGT1A4, UGT16, UGT1A9, and UGT2B7 activities at 200 μM in pooled human liver microsomes. Moreover, eudesmin, fargesin, epimagnolin A, magnolin, and yangambin noncompetitively inhibited UGT1A1-catalyzed SN38 glucuronidation with Ki values of 25.7, 25.3, 3.6, 26.0, and 17.1 μM, respectively, based on kinetic analysis of UGT1A1 inhibition in pooled human liver microsomes. Conversely, the aforementioned tetrahydrofurofuranoid lignans competitively inhibited UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation with 39.8, 24.3, 15.1, 37.6, and 66.8 μM, respectively in pooled human liver microsomes. These in vitro results suggest the necessity of evaluating whether the five tetrahydrofurofuranoid lignans can cause drug–drug interactions with UGT1A1 and UGT1A3 substrates in vivo. |
| وصف الملف: | application/pdf |
| تدمد: | 1999-4923 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d510e1d58135f5fb71d592d51361d68c https://pubmed.ncbi.nlm.nih.gov/33535454 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d510e1d58135f5fb71d592d51361d68c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19994923 |
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