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.

Keywords:

• In vitro metabolism
• prosaikogenin G
• rat liver microsomes
• saikosaponin d
• saikogenin G

Declaration of interest

The authors report no declarations of interest.

The present study is financially supported by the National Natural Science Foundation of China (81403314, 81573626), Fundamental Research Funds for the Central Universities (2015PT032), the Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance (DQCP2015MS03), and the Open Project Program of Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards (201503).