Zhao Huan, Hu Xueli, Guan Shenghong, Cai Jinhong, Li Xiaohan, Fang Jiaxi, Lin Bo, Zhu Wei, Tian Jingkui, Jin Juan, He Qiang, Zhang Xiaoyong
Department of Nephrology, Urology and Nephrology Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Key Laboratory for Molecular Medicine and Chinese Medicine Preparations, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Front Pharmacol. 2024 Mar 14;15:1361643. doi: 10.3389/fphar.2024.1361643. eCollection 2024.
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 Hemsl. CPS-A has anti-inflammatory pharmacological activity, but the substance basis is unknown at present, so studies on the interaction between intestinal microorganisms and CPS-A may clarify the pharmacodynamic substance basis of CPS-A. 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 . 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. 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. 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.
一些草药成分可以重塑肠道微生物群的组成及其代谢产物。与此同时,肠道微生物群也会影响药物代谢。大量研究报道,皂苷在肠道微生物的作用下发生生物转化,从而提高药物疗效和生物利用度。灯盏花苷A是一种三萜皂苷,来源于狭叶珍珠菜。灯盏花苷A具有抗炎药理活性,但目前其物质基础尚不清楚,因此研究肠道微生物与灯盏花苷A之间的相互作用可能会阐明灯盏花苷A的药效物质基础。本研究建立了结肠炎小鼠模型,收集正常小鼠和结肠炎小鼠的无菌粪便,并将灯盏花苷A与两种不同的肠道菌群进行孵育。基于液相色谱-质谱联用技术,研究了肠道微生物介导的灯盏花苷A的代谢过程以及灯盏花苷A对肠道微生物衍生代谢产物的干预作用。实验结果表明,肠道微生物可以介导灯盏花苷A的生物转化,将其代谢为相应的去糖基化产物,从而促进其药效。不仅如此,灯盏花苷A还可以促进结肠炎小鼠肠道微生物群中的脱氧胆酸、组胺、3-羟基十三烷酸和吲哚-3-乙酸等代谢产物的产生。这可能会导致抗结肠炎的效果。灯盏花苷A主要参与硫唑嘌呤和巯嘌呤等代谢途径,这也可能产生有益或有害的影响。本研究对灯盏花苷A与微生物群之间相互作用的研究为口服生物利用度差的中药研究提供了新思路。同时也发现了灯盏花苷A对结肠炎小鼠肠道菌群代谢产物的调节作用。为探索皂苷对结肠炎小鼠的作用机制奠定了基础。