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

• Main Authors: Guo-Ming Dong, Hang Yu, Li-Bin Pan, Shu-Rong Ma, Hui Xu, Zheng-Wei Zhang, Pei Han, Jie Fu, Xin-Yu Yang, Adili Keranmu, Hai-Tao Niu, Jian-Dong Jiang, Yan Wang
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Molecules
• Subjects: timosaponin BII; gut microbiota; metabolites; LC-MS/MS; LC/MS-Q-TOF
• Online Access: https://www.mdpi.com/1420-3049/26/13/3861

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.