ABSTRACT

Objective: Atherosclerotic cardiovascular disease poses a significant health challenge globally. Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition (EndMT) in atherosclerosis. Morin is a bioflavonoid mainly extracted from white mulberry, a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties. This study examines whether morin can alleviate atherosclerosis by suppressing EndMT and seeks to elucidate the underlying mechanism.

Methods: We induced an in vitro EndMT model in human umbilical vein endothelial cells (HUVECs) by stimulating the cells with transforming growth factor β1 (TGF-β1) (10 ng/mL) for 48 h. The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E (ApoE)^–/– mice fed with a high-fat diet (HFD). Mice in the intervention group were given morin (50 mg/kg) orally for 4 weeks. Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase 9 (MMP-9).

Results: Morin inhibited the expression of EndMT markers in a dose-dependent manner in TGF-β1-treated HUVECs. Administering 50 μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced EndMT. Moreover, the overexpression of MMP-9 activated Notch-1 signaling, thereby reversing morin's inhibitory effect on EndMT. In the HFD-induced atherosclerotic ApoE^–/– mice, morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing EndMT. Furthermore, morin demonstrated a strong binding affinity for MMP-9.