Table1_In-depth LC-MS and in-vitro studies of a triterpenoid saponin capilliposide-A metabolism modulation in gut microbiota of mice.pdf

Introduction: Some herbal ingredients can reshape the composition of the gut microbiome as well as its metabolites. At the same time, the gut microbiota can also affect drug metabolism. A large number of studies have reported that saponins are biotransformed under the action of intestinal microorganisms to improve drug efficacy and bioavailability. Capilliposide A is a triterpenoid saponin, which is derived from Lysimachia capillipes Hemsl. CPS-A has anti-inflammatory pharmacological activity, but the substance basis in vivo is unknown at present, so studies on the interaction between intestinal microorganisms and CPS-A may clarify the pharmacodynamic substance basis of CPS-A.
Methods: This study established a colitis mouse model, collected sterile feces from normal mice and colitis mice, and incubated CPS-A with two different intestinal flora in vitro. Based on LC-MS, the metabolic process of CPS-A mediated by intestinal microbes and the intervention effect of CPS-A on intestinal microbiome derived metabolites were studied.
Results: The results of experiments indicate that intestinal microorganisms can mediate the biotransformation of CPS-A and metabolize it into corresponding deglycosylation products, thereby promoting its drug effect. Not only that, CPS-A can also promote metabolites such as Deoxycholic acid, Histamine, 3-Hydroxytridecanoic acid, and Indole-3-acetic acid in the intestinal microbiota of mice with colitis. This may result in anti-colitis effects. CPS-A mainly involved in metabolic pathways such as azathioprine and mercaptopurine, which may also have beneficial or adverse effects.
Discussion: This study on the interaction between CPS-A and microbiota provides a new idea for the study of traditional Chinese medicine with poor oral bioavailability. The regulatory effect of CPS-A on the metabolites of intestinal flora in colitis mice was also found. It laid a foundation for exploring the mechanism of action of saponins on colitis mice.

引言：部分草本成分可重塑肠道微生物组（gut microbiome）及其代谢物的组成。与此同时，肠道微生物群（gut microbiota）亦可影响药物代谢。已有大量研究表明，皂苷（saponins）可在肠道微生物的作用下发生生物转化，从而提升药物疗效与生物利用度。毛蕊草苷A（Capilliposide A，简称CPS-A）是一种来源于过路黄（Lysimachia capillipes Hemsl.）的三萜类皂苷（triterpenoid saponin），其具有抗炎药理活性，但目前其体内药效物质基础尚不明确，因此开展肠道微生物与CPS-A的相互作用研究，或可阐明CPS-A的药效物质基础。
方法：本研究构建结肠炎小鼠模型，收集正常小鼠与结肠炎小鼠的无菌粪便，体外将CPS-A与两种不同的肠道菌群进行共孵育。基于液相色谱-质谱联用（LC-MS）技术，本研究分析了肠道微生物介导的CPS-A代谢过程，以及CPS-A对肠道微生物组来源代谢物的干预作用。
结果：实验结果表明，肠道微生物可介导CPS-A发生生物转化，将其代谢为相应的去糖基化产物，进而增强其药效活性。不仅如此，CPS-A还可促进结肠炎小鼠肠道菌群产生脱氧胆酸（Deoxycholic acid）、组胺（Histamine）、3-羟基十三烷酸（3-Hydroxytridecanoic acid）及吲哚-3-乙酸（Indole-3-acetic acid）等代谢物，这可能是其发挥抗结肠炎作用的潜在机制。此外，CPS-A主要参与硫唑嘌呤（azathioprine）与巯嘌呤（mercaptopurine）相关代谢通路，该过程或同时存在有益与不良影响。
讨论：本研究针对CPS-A与肠道微生物群的相互作用，为口服生物利用度较低的中药研究提供了新思路。本研究同时揭示了CPS-A对结肠炎小鼠肠道菌群代谢物的调控作用，为阐明三萜类皂苷治疗结肠炎的作用机制奠定了基础。