Ethanol extract of Pueraria lobata improve acute myocardial infarction in rats via regulating gut microbiota and bile acid metabolism

BACKGROUND AND AIM: Acute myocardial infarction (AMI) is a multifactorial disease with high mortality rate worldwide. Ethanol extract of Pueraria lobata (EEPL) has been widely used in treating cardiovascular diseases in China. This study aimed to explore the underlying therapeutic mechanism of EEPL in AMI rats. EXPERIMENTAL PROCEDURE: We first evaluated the anti-AMI efficacy of EEPL through immunohistochemistry staining and biochemical indexes. Then, UPLC-MS/MS, 16S rDNA, and shotgun metagenomic sequencing were used to analyze the alterations in bile acid metabolism and intestinal flora. Finally, the influence of EEPL on ilem bile acid metabolism, related enzymes expression, and transporter proteins expression in rats were verified by mass spectrometry image and ELISA. KEY RESULTS: The results showed that EEPL can reduce cardiac impairment in AMI rats. Besides, EEPL effectively increased bile acid levels and regulated gut microbiota disturbance in AMI rats via increasing CYP7A1 expression and restoring intestinal microbiota diversity, separately. Moreover, it can increase bile acids reabsorption and fecal excretion through inhibiting FXR-FGF15 signaling pathway and increasing OST-α expression, which associated with Lachnoclostridium. CONCLUSIONS AND IMPLICATIONS: Our findings demonstrated that EEPL alleviated AMI partially by remediating intestinal dysbiosis and promoting bile acid biosynthesis, which provided new targets for AMI treatment.