Objective Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans. Design The impact of PU on AS was examined in ApoE −/− mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with Prevotella copri ( P. copri ) were employed. Results PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into ApoE−/− mice fed HFD. Specifically, PU reduced the abundance of P. copri , which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of P. copri undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of P. copri and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased P. copri levels and reduced TMAO concentrations in patients with carotid artery plaque. Conclusion PU may provide therapeutic benefits in combating AS by targeting P. copri and its production of TMA. Trial registration number ChiCTR1900022488. Data are available in a public, open access repository. Data are available in a public, open access repository (). All data relevant to the study are included in the article or uploaded as supplementary information. Other data sets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.

中文翻译：

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葛根素通过抑制 Prevotella copri 及其三甲胺的产生来缓解动脉粥样硬化


目的 葛根素 （PU） 是一种天然化合物，口服生物利用度有限，但在治疗动脉粥样硬化 （AS） 方面显示出前景。然而，其治疗效果的确切机制仍不完全清楚。本研究旨在探讨 PU 及其缓解小鼠和人类 AS 的作用机制。设计 在饲喂高脂饮食 （HFD） 的 ApoE −/- 小鼠和颈动脉斑块的人类患者中检查了 PU 对 AS 的影响。为了探讨 PU 相关肠道微生物群与 AS 之间的因果关系，采用了粪便微生物群移植 （FMT） 和小鼠普雷沃氏菌 （P. copri） 的单定植。结果 PU 通过调节肠道菌群来缓解 AS，PU 处理小鼠肠道菌群组成的改变和饲喂 HFD 的 ApoE-/− 小鼠在 FMT 后 AS 的改善证明了这一点。具体来说，PU 降低了 P. copri 的丰度，它通过产生三甲胺 （TMA） 加剧了 AS。P. copri 的长期单定植破坏了 PU 对 AS 的有益作用。在临床上，AS 患者的斑块评分与 P. copri 丰度和血浆三甲胺-N-氧化物 （TMAO） 水平呈正相关。为期 1 周的 PU 口服干预可有效降低颈动脉斑块患者的 P. copri 水平并降低 TMAO 浓度。结论 PU 可能通过靶向 P. copri 及其产生 TMA 为对抗 AS 提供治疗益处。试验注册号 ChiCTR1900022488。数据在公共、开放访问存储库中可用。数据在公共、开放访问存储库 （） 中可用。与研究相关的所有数据都包含在文章中或作为补充信息上传。 在当前研究期间生成和/或在当前研究期间分析的其他数据集可应合理要求从通讯作者处获得。