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Molecules 2017, 22(4), 670; doi:10.3390/molecules22040670

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

Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 14462, Korea
Central R&D Institute, YUNGJIN PHARM. CO., LTD., Suwon 16229, Korea
Author to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 6 April 2017 / Revised: 17 April 2017 / Accepted: 19 April 2017 / Published: 22 April 2017
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [3774 KB, uploaded 22 April 2017]   |  


Verproside, an active iridoid glycoside component of Veronica species, such as Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica, possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and cytostatic activities. Verproside is metabolized into nine metabolites in human hepatocytes: verproside glucuronides (M1, M2) via glucuronidation, verproside sulfate (M3) via sulfation, picroside II (M4) and isovanilloylcatalpol (M5) via O-methylation, M4 glucuronide (M6) and M4 sulfate (M8) via further glucuronidation and sulfation of M4, and M5 glucuronide (M7) and M5 sulfate (M9) via further glucuronidation and sulfation of M5. Drug-metabolizing enzymes responsible for verproside metabolism, including sulfotransferase (SULT) and UDP-glucuronosyltransferase (UGT), were characterized. The formation of verproside glucuronides (M1, M2), isovanilloylcatalpol glucuronide (M7), and picroside II glucuronide (M6) was catalyzed by commonly expressed UGT1A1 and UGT1A9 and gastrointestinal-specific UGT1A7, UGT1A8, and UGT1A10, consistent with the higher intrinsic clearance values for the formation of M1, M2, M6, and M7 in human intestinal microsomes compared with those in liver microsomes. The formation of verproside sulfate (M3) and M5 sulfate (M9) from verproside and isovanilloylcatalpol (M5), respectively, was catalyzed by SULT1A1. Metabolism of picroside II (M4) into M4 sulfate (M8) was catalyzed by SULT1A1, SULT1E1, SULT1A2, SULT1A3, and SULT1C4. Based on these results, the pharmacokinetics of verproside may be affected by the co-administration of relevant UGT and SULT inhibitors or inducers. View Full-Text
Keywords: verproside; in vitro metabolism; UDP-glucuronosyltransferase; sulfotransferase verproside; in vitro metabolism; UDP-glucuronosyltransferase; sulfotransferase

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MDPI and ACS Style

Kim, J.-H.; Hwang, D.-K.; Moon, J.-Y.; Lee, Y.; Yoo, J.S.; Shin, D.H.; Lee, H.S. Multiple UDP-Glucuronosyltransferase and Sulfotransferase Enzymes are Responsible for the Metabolism of Verproside in Human Liver Preparations. Molecules 2017, 22, 670.

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