Molecules 2012, 17(10), 11990-12002; doi:10.3390/molecules171011990
Article

In Vitro and in Vivo Metabolism of Verproside in Rats

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Received: 3 September 2012; in revised form: 28 September 2012 / Accepted: 8 October 2012 / Published: 12 October 2012
(This article belongs to the Special Issue Active Pharmaceutical Ingredients)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Verproside, a catalpol derivative iridoid glycoside isolated from Pseudolysimachion rotundum var. subintegrum, is a biologically active compound with anti-inflammatory, antinociceptic, antioxidant, and anti-asthmatic properties. Twenty-one metabolites were identified in bile and urine samples obtained after intravenous administration of verproside in rats using liquid chromatography-quadrupole Orbitrap mass spectrometry. Verproside was metabolized by O-methylation, glucuronidation, sulfation, and hydrolysis to verproside glucuronides (M1 and M2), verproside sulfates (M3 and M4), picroside II (M5), M5 glucuronide (M7), M5 sulfate (M9), isovanilloylcatalpol (M6), M6 glucuronide (M8), M6 sulfate (M10), 3,4-dihydroxybenzoic acid (M11), M11 glucuronide (M12), M11 sulfates (M13 and M14), 3-methyoxy-4-hydroxybenzoic acid (M15), M15 glucuronides (M17 and M18), M15 sulfate (M20), 3-hydroxy-4-methoxybenzoic acid (M16), M16 glucuronide (M19), and M16 sulfate (M21). Incubation of verproside with rat hepatocytes resulted in thirteen metabolites (M1–M11, M13, and M14). Verproside sulfate, M4 was a major metabolite in rat hepatocytes. After intravenous administration of verproside, the drug was recovered in bile (0.77% of dose) and urine (4.48% of dose), and O-methylation of verproside to picroside II (M5) and isovanilloylcatalpol (M6) followed by glucuronidation and sulfation was identified as major metabolic pathways compared to glucuronidation and sulfation of verproside in rats.
Keywords: verproside metabolism; rat bile; rat urine; rat hepatocytes; LC-HRMS
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MDPI and ACS Style

Kim, M.G.; Hwang, D.-K.; Jeong, H.-U.; Ji, H.Y.; Oh, S.-R.; Lee, Y.; Yoo, J.S.; Shin, D.H.; Lee, H.S. In Vitro and in Vivo Metabolism of Verproside in Rats. Molecules 2012, 17, 11990-12002.

AMA Style

Kim MG, Hwang D-K, Jeong H-U, Ji HY, Oh S-R, Lee Y, Yoo JS, Shin DH, Lee HS. In Vitro and in Vivo Metabolism of Verproside in Rats. Molecules. 2012; 17(10):11990-12002.

Chicago/Turabian Style

Kim, Min G.; Hwang, Deok-Kyu; Jeong, Hyeon-Uk; Ji, Hye Y.; Oh, Sei-Ryang; Lee, Yongnam; Yoo, Ji S.; Shin, Dae H.; Lee, Hye S. 2012. "In Vitro and in Vivo Metabolism of Verproside in Rats." Molecules 17, no. 10: 11990-12002.

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