Multiple UDP-Glucuronosyltransferase and Sulfotransferase Enzymes are Responsible for the Metabolism of Verproside in Human Liver Preparations

Kim, Ju-Hyun; Hwang, Deok-Kyu; Moon, Joon‐Kwan; Lee, Yongnam; Yoo, Ji Seok; Shin, Dae Hee; Lee, Hye Suk

doi:10.3390/molecules22040670

Cited by 3 publications

(1 citation statement)

References 26 publications

(37 reference statements)

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“…It is important to establish the comparative metabolism and drug-metabolizing enzymes of active constituents for a full characterization of its pharmacokinetics, pharmacodynamics, and toxicity. The characterization of drug-metabolizing enzymes such as CYPs, carboxylesterases (CESs), UDP-glucuronosyltransferases (UGTs), and sulfotransferases (SULTs) responsible for the metabolism of a drug may reveal inter-individual variability in drug metabolism and the potential drug interactions [17,18,19]. However, catalposide metabolism has not been studied in humans and animals.…”

Section: Introductionmentioning

confidence: 99%

Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes

et al. 2019

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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.

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Section: Introductionmentioning

confidence: 99%

Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes

et al. 2019

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Pharmacogenetics of human sulfotransferases and impact of amino acid exchange on Phase II drug metabolism

Isvoran

Peng

Ceauranu

et al. 2022

Drug Discovery Today

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Metabolism of Dietary Carbohydrates by Intestinal Bacteria

Gülşan

Nowshad

Jayaraman

et al. 2022

Metabolism of Nutrients by Gut Microbiota

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Carbohydrates are significant components of both plant- and animal-based human diets. Depending on the type of diet, calories from carbohydrates can account for more than 70% of total daily energy intake of human adults. Bacteria residing in the colon have greater access to complex carbohydrates, as these molecules are only partially digested in the stomach and not fully absorbed in the small intestine. Microbial metabolism of these dietary microbiota-accessible carbohydrates (MACs) in the colon is important as organic acids such as short-chain fatty acids (SCFAs) produced upon fermentation of MACs are important mediators of host physiology, including promoting intestinal epithelial barrier integrity and development of the immune system. Here we review the microbial metabolism of three different MACs (dietary fiber, polyphenols, and amino sugars) and the enzymes involved in their metabolism. We also discuss advances in tools such as metabolomics and metabolic modeling that are needed for identifying and characterizing products of MAC metabolism by gut bacteria, and suggest future directions of research for elucidating the mechanisms whereby these products influence host physiological processes.

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Multiple UDP-Glucuronosyltransferase and Sulfotransferase Enzymes are Responsible for the Metabolism of Verproside in Human Liver Preparations

Cited by 3 publications

References 26 publications

Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes

Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes

Pharmacogenetics of human sulfotransferases and impact of amino acid exchange on Phase II drug metabolism

Metabolism of Dietary Carbohydrates by Intestinal Bacteria

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