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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 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.
- CARDIOVASCULAR DISEASE
Data availability statement
Data are available in a public, open access repository. Data are available in a public, open access repository (https://doi.org/10.5061/dryad.sf7m0cgfg). 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.
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Data availability statement
Data are available in a public, open access repository. Data are available in a public, open access repository (https://doi.org/10.5061/dryad.sf7m0cgfg). 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.
Footnotes
Z-HL, JW, JY and Y-HZ contributed equally.
Correction notice This article has been corrected since it published Online First. Author's Ping-Zhen Yang and Hong-Wei Zhou have been added as corresponding authors.
Contributors Z-HL, JW, JY and Y-HZ designed and supervised the study. JW, JY and Y-HZ collected and analysed the data. Q-YH, H-FS and Y-QH recruited subjects and collected samples. YD, Z-PW, Z-YW, G-HL, XL, R-HT and J-CD conducted animal, bacterial cultivation and mass spectrometry experiments. Z-HL wrote the manuscript. H-WZ and P-ZY contributed to text revision and discussion. ZL acts as guarantor of this study. All authors discussed the results and approved the manuscript.
Funding This work was supported by grants from the National Key R&D Programme of China (2022YFA0806400), Guangzhou Key Research Programme on Brain Science (202206060001) and the National Natural Science Foundation of China (81925026 and 82130068) to H-WZ, the National Natural Science Foundation of China (82200936) and the Guangdong Basic and Applied Basic Research Foundation (SL2023A04J02020) to ZL, the National Natural Science Foundation of China (82200442) to Z-HL.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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