Puerarin alleviates atherosclerosis via the inhibition ofand its trimethylamine production.

Abstract

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 inmice 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() 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 intomice fed HFD. Specifically, PU reduced the abundance of, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation ofundermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance ofand plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreasedlevels and reduced TMAO concentrations in patients with carotid artery plaque. CONCLUSION: PU may provide therapeutic benefits in combating AS by targetingand its production of TMA. TRIAL REGISTRATION NUMBER: ChiCTR1900022488.