In vitro metabolism study of saikosaponin d and its derivatives in rat liver microsomes

Abstract

1. Saikosaponins, one of the representative bioactive ingredients in Radix Bupleuri, possess hepatoprotective, anti-inflammatory, antiviral, antitumor, and other pharmacological activities. Up to now, few studies focused on the further metabolism of saikosaponins and their secondary metabolites absorbed into the circulatory system. 2. To understand the in vivo efficacy of saikosaponin d, the in vitro metabolism of saikosaponin d, and its two derivatives formed in the gastrointestinal tract, prosaikogenin G and saikogenin G was investigated in rat liver microsomes, respectively. 3. Fifteen metabolites were detected using high-performance liquid chromatography hybrid ion trap and time-of-flight mass spectrometry and triple-quadrupole mass spectrometry, and the predominant metabolic reactions were hydroxylation, carboxylation and combinations of these steps on the aglycone moiety. 4. The metabolic pathways of saikosaponin d, prosaikogenin G, and saikogenin G were proposed in vitro and the results contribute to the understanding of saikosaponins in vivo metabolism.

Identification and Analysis of Compound Profiles of Sinisan Based on ‘Individual Herb, Herb-Pair, Herbal Formula’ before and after Processing Using UHPLC-Q-TOF/MS Coupled with Multiple Statistical Strategy

“…94 was clearly observed in VPBR, VPBR-VPPRA herb-pair, SNS-containing VPBR and VPPRA, and SNS, and almost undetectable in BR and BR-PRA herb-pair. According to the fragmentations in both positive and negative ion modes and other reports [22,23,24], we suggested that peak No. 94 is SSg.…”

A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins

“…The metabolic routes are different depends on different administrative routes . The same research group also confirmed that, similar to SSa, SSd and its derivatives PSGG and SGG are all transformed into phase-1 metabolites through liver microsomeand CYP enzymes-mediated oxidation, including dehydrogenation, monooxidation, and carboxylation and combination of these processes on aglycone moiety (Yu et al, 2017).…”

“…Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was employed to simultaneously detect the contents of SSs (SSa, SSc and SSb2) in rat plasma (Xu et al, 2012b). Most recently, both SSa and SSd, as well as 15 and 16 metabolites, respectively, were simultaneously identified in various bio-samples, including plasma, bile, feces and urines, by using state-of-the-art liquid chromatography-diode array detector coupled with hybrid ion trap-time-of-flight mass spectrometry (LC-DAD-IT-TOF-MS) analysis Yu et al, 2017).…”

Z0 ion from saikosaponins with 16 α‐OH and Y0‐H2O from saikosaponins with 16 β‐OH may underlie their different dissociation patterns of [aglycone − H2O + H]+

“…However, it is the dissociation patterns in the positive ion mode which provide the direct structural information about aglycones that pose a great challenge to elucidate. For example, the challenge still exists in characterizing and identifying the in vitro metabolites of SSd even after the characterization and identification of the in vivo metabolites of its epimer, SSa, had been reported . Not surprisingly, it will become more difficult in the case of metabolism research when the herbal medicines containing Bupleurum species are administered.…”