Puerarin alleviates atherosclerosis via the inhibition ofPrevotella copriand its trimethylamine production

Abstract

ObjectivePuerarin (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.DesignThe impact of PU on AS was examined inApoE−/−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 withPrevotella copri(P. copri) were employed.ResultsPU 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 intoApoE−/−mice fed HFD. Specifically, PU reduced the abundance ofP. copri, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation ofP. copriundermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance ofP. copriand plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreasedP. coprilevels and reduced TMAO concentrations in patients with carotid artery plaque.ConclusionPU may provide therapeutic benefits in combating AS by targetingP. copriand its production of TMA.Trial registration numberChiCTR1900022488.