Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes
| العنوان: | Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes |
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| المؤلفون: | Joo Young Lee, Yong-Yeon Cho, Ju-Hyun Kim, Deok-Kyu Hwang, Sunjoo Kim, Won-Gu Choi, Yongho Shin, Hye Suk Lee, Han Chang Kang |
| المصدر: | Pharmaceutics Volume 11 Issue 7 Pharmaceutics, Vol 11, Iss 7, p 355 (2019) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | chemistry.chemical_classification, UGT1A6, 0303 health sciences, Sulfotransferase, Glucuronidation, Pharmaceutical Science, lcsh:RS1-441, sulfotransferase, carboxylesterase, 030226 pharmacology & pharmacy, Article, catalposide, in vitro human metabolism, lcsh:Pharmacy and materia medica, 03 medical and health sciences, Carboxylesterase, Metabolic pathway, 0302 clinical medicine, Enzyme, chemistry, Biochemistry, Microsome, Glucuronide, UDP-glucuronosyltransferase, 030304 developmental biology |
| الوصف: | Catalposide, an active component of Veronica species such as Catalpa ovata and Pseudolysimachion lingifolium, exhibits anti-inflammatory, antinociceptic, anti-oxidant, hepatoprotective, and cytostatic activities. We characterized the in vitro metabolic pathways of catalposide to predict its pharmacokinetics. Catalposide was metabolized to catalposide sulfate (M1), 4-hydroxybenzoic acid (M2), 4-hydroxybenzoic acid glucuronide (M3), and catalposide glucuronide (M4) by human hepatocytes, liver S9 fractions, and intestinal microsomes. M1 formation from catalposide was catalyzed by sulfotransferases (SULTs) 1C4, SULT1A1*1, SULT1A1*2, and SULT1E1. Catalposide glucuronidation to M4 was catalyzed by gastrointestine-specific UDP-glucuronosyltransferases (UGTs) 1A8 and UGT1A10 M4 was not detected after incubation of catalposide with human liver preparations. Hydrolysis of catalposide to M2 was catalyzed by carboxylesterases (CESs) 1 and 2, and M2 was further metabolized to M3 by UGT1A6 and UGT1A9 enzymes. Catalposide was also metabolized in extrahepatic tissues genetic polymorphisms of the carboxylesterase (CES), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes responsible for catalposide metabolism may cause inter-individual variability in terms of catalposide pharmacokinetics. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics11070355 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::753a27c5014b3942c6267fcb65912c95 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....753a27c5014b3942c6267fcb65912c95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19994923 |
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| DOI: | 10.3390/pharmaceutics11070355 |