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

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.

Zi Shen Wan Fang Attenuates Neuroinflammation and Cognitive Function Via Remodeling the Gut Microbiota in Diabetes-Induced Cognitive Impairment Mice

“…Although accumulative studies confirmed that berberine, the main alkaloid component of Phellodendri Chinensis Cortex, can protect cognitive function (Aski et al, 2018;Shinjyo et al, 2020;Yi et al, 2021), subsequent studies gradually recognized that regulating intestinal flora may be the initial link of berberine improving cognitive function (Zhang et al, 2020b;Habtemariam, 2020). The ZSWF components metabolized by intestinal flora of DCI mice may be saponins in Anemarrhenae Rhizoma (Tian et al, 2016;Dong et al, 2021). Furthermore, besides the immune signaling pathway investigated in this study, the mechanism of ZSWF regulating intestinal flora to improve DCI may also include the following aspects: first, regulating the tryptophan-kynurenine metabolic pathway.…”

Combination of ultra‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry and network pharmacology to reveal the key effective compounds and mechanism of Shengxian decoction for ameliorating doxorubicin cardiotoxicity

“…Compound 11, characterized by the molecular formula of C 45 H 76 O 19 , fragment ions at m/z 901.4813 [M‐H‐H 2 O] − , m/z 757.4384 [M‐H‐C 6 H 10 O 5 ] − , and m/z 595.3843 [M‐H‐C 6 H 10 O 5 ‐C 6 H 10 O 5 ] − , was identified as timosaponin B‐II according to the reference substance and reported data [30]. It could be detected in all bio‐samples of CHF rats (Figure 7).…”

Analysis of the therapeutic effect of Dimu Ningshen (TCM formula) on attention deficit hyperactivity disorder based on gut microbiota and serum metabolomics

“…According to research reports, these saponins have antidepressant and antineuritis pharmacological activities. Guo-Ming Dong et al found that the gut microbiota has a strong metabolic effect on timosaponin BII, which can be converted into 7 characteristic metabolites [ 36 ]. Considering that the phytochemical-microbiota interaction is the key to drug metabolism, we will focus our research on the influence of DMNS on the abundance, diversity and function of the gut microbiota of ADHD rats.…”