Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.

绞股蓝皂甙，提取物绞股蓝yixingense, 传统上被规定用于改善亚洲民间和当地传统医学医院的代谢综合征。然而，其作用机制仍不清楚。在这项工作中，我们的结果表明，长期服用 2α-OH-原人参二醇 (GP2)，一种绞股蓝皂苷的体内代谢物，通过改善肠道 L 细胞功能保护小鼠免受高脂饮食诱导的肥胖和改善葡萄糖耐量。从机制上讲，GP2 处理抑制胆盐水解酶的酶活性并调节肠道微生物群的比例，从而导致肠道中牛磺-β-鼠胆酸 (TβMCA) 的积累增加。TβMCA 通过降低核受体法尼醇 X 受体 (FXR) 的转录活性来诱导 GLP-1 的产生和分泌。将 GP2 重塑的粪便微生物群移植到抗生素治疗的小鼠中也增加了肠道 TβMCA 含量并改善了肠道 L 细胞功能。这些发现表明 GP2 至少部分通过肠道微生物群重塑通过肠道 FXR/GLP-1 轴改善代谢综合征，并且还表明 GP2 可作为代谢综合征的有前途的口服治疗剂。