Puerarin alleviates atherosclerosis via the inhibition of and its trimethylamine production.

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 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 () 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 mice fed HFD. Specifically, PU reduced the abundance of , which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased levels and reduced TMAO concentrations in patients with carotid artery plaque.

CONCLUSION

PU may provide therapeutic benefits in combating AS by targeting and its production of TMA.

TRIAL REGISTRATION NUMBER

ChiCTR1900022488.