title: In vitro and in vivo metabolism of verproside in rats.
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.
authors.affiliation: Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.forename: Deok-Kyu
authors.initials: DK
authors.lastname: Hwang
authors.forename: Hyeon-Uk
authors.initials: HU
authors.lastname: Jeong
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Ji
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.forename: Yongnam
authors.initials: Y
authors.lastname: Lee
authors.forename: Ji Seok
authors.initials: JS
authors.lastname: Yoo
authors.forename: Dae Hee
authors.initials: DH
authors.lastname: Shin
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D022781:Hepatocytes / Q000378:metabolism; D057888:Iridoid Glucosides / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D057888:Iridoid Glucosides; C512483:verproside