A combination of notoginseng and safflower improves myocardial ischemia via modulating FXR and bile acid metabolism

Notoginseng and safflower, well-known medicinal and edible herbs, promote blood circulation and resolve blood stasis. The combination of notoginseng total saponins and safflower total flavonoids (CNS) provides significant therapeutic effects against myocardial ischemia. However, the exact mechanisms underlying its cardioprotective properties remain unclear. This study integrated metabolomics, 16S rRNA sequencing, and molecular biology techniques to explore the mechanism by which CNS ameliorates myocardial ischemia. Our findings demonstrate that CNS exerts anti-myocardial ischemic effects by activating FXR, reducing tissue bile acids (BAs) accumulation, and promoting fecal BAs excretion. In vitro experiments demonstrated that FXR activation enhanced, whereas FXR inhibition attenuated the cardioprotective effects of CNS. Furthermore, FXR −/− mouse experiments validated that deletion of FXR attenuated both the therapeutic effects of CNS on myocardial ischemic injury and its regulatory effects on BA homeostasis. These findings provide a novel theoretical basis supporting CNS as a therapeutic agent for myocardial ischemia.