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.

Metabolic mapping of Schisandra sphenanthera extract and its active lignans using a metabolomic approach based on ultra high performance liquid chromatography with high‐resolution mass spectrometry

“…It is believed that compounds with similar structures have similar metabolic rules, and the metabolism in vitro can be used to predict the metabolic pathways in vivo to some extent [26]. Recently, it was reported that WZ's active lignans including SinA, SolA and SolB were the substrates of CYP3A [6], we performed the in vitro study using mice liver microsome, which could highly express drug-metabolizing phase I enzymes [27].…”

Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma

“…Recently, we reported that verproside is a major biologically active compound of this plant, showing potent anti-inflammatory, antioxidant, and anti-asthmatic activities [33, 34]. However, verproside is predominantly metabolized to picroside II in vivo [35]. These information led us to evaluate the protective effects of picroside II on airway inflammation.…”

Characterization of picroside II metabolites in rats by ultra-high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry

“…M01, M02 and M09 were found as the circulating metabolites in rat plasma, which may be associated with its activity. Although the biotransformation on picroside II have been reported in previous studies [23][24], our observations provided insights into the in vivo disposition of picroside II as a total of six metabolites were newly identified (M03-M08). Further studies should focus on the preparation of the newly identified principal metabolites and the evaluation of their hepatoprotective effects and toxicities.…”