Sophoricoside enhances reparative macrophage polarization to promote cardiac repair postmyocardial infarction through PPAR-γ.

BACKGROUND

Myocardial infarction (MI) represents a significant cardiovascular condition that endangers human health. This research aimed to explore the therapeutic effectiveness of sophoricoside (Sop) using a mouse model of MI.

METHODS

To conduct this investigation, a mice model of MI was utilized, and Sop was delivered through oral administration via gavage. The area of MI in mice was assessed by Masson trichrome staining. Cardiac systolic function and left ventricular dilatation were measured by cardiac ultrasound. Picrosirius red staining and Masson's trichrome staining were performed to detect the collagen deposition and fibrosis. The expressions of reparative macrophage-associated markers were measured by quantitative real-time PCR. Western blotting was utilized to sense expression of lysyl oxidase (LOX), peroxisome proliferator-activated receptor γ (PPAR-γ), and collagen 1. Flow cytometry was performed to detect the number of macrophages. The Cell Counting Kit-8 assay was performed to detect Sop's cytotoxicity. The M2 polarization and efferocytosis in mice model of MI was verified by immunofluorescence assay.

RESULTS

Sop significantly reduced myocardial infarct size. Cardiac ultrasound evaluation further showed that Sop was effective in improving cardiac systolic dysfunction and left ventricular dilatation. In addition, Sop significantly promoted efferocytosis and reparative M2 macrophage polarization and inhibited glycolytic metabolic pathways, thereby promoting cardiac tissue repair. It was further found that Sop could obviously promote expression of PPAR-γ in the nucleus. GW9662 partially reversed the improvement of Sop on cardiac repair and reparative macrophage polarization in MI mice.

CONCLUSION

In summary, this study elucidates that Sop enhances reparative macrophage polarization to promote cardiac repair post-MI through PPAR-γ.