Prunella vulgaris polyphenols alleviate atherosclerosis by regulating lipid metabolism via suppressing STAT3 and activating the PI3K-Akt pathway.

Atherosclerosis (AS), a leading cause of cardiovascular diseases, remains a major challenge due to the lack of effective preventive and therapeutic strategies. This study investigated the anti-atherosclerotic effects and underlying mechanisms of Prunella vulgaris polyphenols (PVPs). PVPs were found to significantly reduce lipid deposition in the aorta and enhance plaque stability by increasing fibrous cap thickness and collagen content, while simultaneously reducing MMP-9 and CD68 protein expressions. Moreover, PVPs alleviated hepatic lipid accumulation by upregulating ABCA1 and downregulating SREBP1 protein expressions. The PI3K-Akt pathway was identified as a key mechanism underlying the therapeutic effects of PVPs, with STAT3 predicted as a critical target involved in lipid metabolism. These predictions were further validated experimentally, demonstrating that PVPs effectively inhibited STAT3 activation while enhancing the PI3K-Akt pathway. Taken together, these findings reveal that PVPs exert anti-atherosclerotic effects by modulating lipid metabolism through the inhibition of STAT3 and activation of the PI3K-Akt pathway.