The findings suggest that Volvalerenic A, the primary metabolite in KYXC, can enhance the accumulation of lipids, mitigate the inflammatory milieu, alleviate mitochondrial damage, and eventually impede the progression of atherosclerosis by activating the PGC-1α/Sirt3/Epac1 signaling pathway. This evidence concerns the gene RAPGEF3 and atherosclerosis.