A UPLC-MS/MS method for simultaneous quantification of pairs of oleanene- and ursane-type triterpenoid saponins and their major metabolites in mice plasma and its application to a comparative pharmacokinetic study.

Wenwen Zhao,Weiwei Guo,Xia Wu,Xiaoqing Chen,Kui Luo,Jie Yang,Zongyang Liu,Wei Gao

doi:10.1039/c8ra00739j

Abstract

Ilexhainanoside D (IhD) and Ilexsaponin A1 (IsA) are a pair of oleanene- and ursane-type triterpenoid saponins, which are also the main bioactive pharmaceutical ingredients of Ilex hainanensis Merr. with great potential to treat non-alcoholic fatty liver disease (NAFLD). The pharmacokinetics of four representative triterpenoids in mice were investigated in this study, which were IhD, IsA and their major metabolites 3β, 19α-dihydroxyolean-12-ene-24, 28-dioic acid (ID) and Ilexgenin A (IA). A sensitive and accurate UPLC-MS/MS method was developed and validated for the simultaneous quantitative determination of IhD, IsA, ID and IA in control and NAFLD mice plasma after oral administration of the total saponins of I. hainanensis (the contents of IhD and IsA were 41.6% and 54.4%, respectively). The results revealed that the pharmacokinetic behaviors could be changed in NAFLD mice compared with control mice. The area under the plasma drug concentration–time curve and maximum plasma concentrations of IhD and IsA were greatly decreased in the NAFLD mice. However, the main residence time of ID and IA were greatly increased in the NAFLD mice. The results revealed that this method could be used to analyze two pairs of triterpenoid isomers in biological samples.

Highlights

IntroductionThey are the major triterpenoid glycosides and aglycones in the leaves of Ilex hainanensis Merr
Ilexhainanoside D (IhD), Ilexsaponin A1 (IsA), 3b, 19adihydroxyolean-12-ene-24, 28-dioic acid (ID) and Ilexgenin A (IA) are two pairs of oleanene- and ursane-type triterpenoids
It has been demonstrated that the extracts from I. hainanensis could reduce the levels of blood lipids and improve diet-induced non-alcoholic fatty liver disease (NAFLD).[2]

Summary

Introduction

They are the major triterpenoid glycosides and aglycones in the leaves of Ilex hainanensis Merr. Phytochemical studies revealed that main components of I. hainanensis were triterpene glycosides, triterpenes and avonoids.[4] IhD and IsA, ID and IA are the major bioactive constituents in I. hainanensis, which show great pharmacological effects, such as cardiovascular and cerebrovascular protection activities in mice[5] and protective effects against NAFLD in rats.[6] IhD and IsA usually exist in pairs in the plants, and their contents are 0.5–1% and 1–4%, respectively.[7]

Methods

Results

Conclusion