Biotransformation of Timosaponin BII into Seven Characteristic Metabolites by the Gut Microbiota

Guo-Ming Dong,Zheng-Wei Zhang,Pei Han,Hui Xu,Jian-Dong Jiang,Jie Fu,Adili Keranmu,Hai-Tao Niu,Yan Wang,Xin-Yu Yang,Shu-Rong Ma,Hang Yu,Li-Bin Pan

doi:10.3390/molecules26133861

Abstract

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1–M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.

Highlights

Anemarrhena saponins are steroidal saponins derived from the plant Anemarrhena asphodeloides Bge of the family Liliaceae
A method for quantifying timosaponin BII was established using High-Performance Liquid Chromatograph (HPLC)-MS/MS to explore whether timosaponin BII can be metabolized by gut microbiota
Anemarrhenae Rhizoma is a traditional Chinese medicine commonly used in Chinese medicinal formulae and has the functions of clearing heat, purging fire, nourishing yin and moisturizing dryness

Summary

Introduction

Anemarrhena saponins are steroidal saponins derived from the plant Anemarrhena asphodeloides Bge of the family Liliaceae. Studies have shown that Anemarrhena saponins have a variety of pharmacological activities, including effects on the symptoms of dementia, improvements in learning and memory, remission of depression, vascular protection, anticoagulant and antithrombotic activities, regulation of glucose and lipid metabolism, and antitumor activities [1,2,3,4,5,6,7]. More than 40 Anemarrhena saponins have been reported and widely exist in Anemarrhena asphodeloides Bge [8]. Timosaponin BII has been reported to have pharmacological activities such as effects on the symptoms of dementia, inhibiting platelet aggregation, anti-inflammatory activity, and improving learning and memory functions [4,10,11,12]. It has been shown that the parent drug of timosaponin BII itself, and its metabolites may have pharmacological activity

Objectives

Methods

Results

Conclusion