In this study, four previously undescribed flavonoids, named epimesatines P (), Q (), R (), and S (), were isolated from the aerial parts of Maxim. Their structures and absolute configurations were confirmed via spectroscopic analyses, quantum chemical electronic circular dichroism (ECD) calculations, Mo(OAc)-induced ECD, and Rh(OCOCF)-induced ECD experiments. Epimesatines Q and R were characterized by the presence of furan rings. A cytotoxicity assay demonstrated that epimesatines P-S exhibited significant inhibitory effects on the viability of MCF-7 human breast cancer cells, with IC values ranging from 1.27 to 50.3 μM. Notably, epimesatines Q and R exhibited superior efficacy against MCF-7 cells compared to epimesatines P and S, suggesting that the presence of furan rings may enhance their activity against MCF-7 cells. Specifically, epimesatine Q displayed a more potent inhibitory effect at 1.27 μM compared to a positive control, docetaxel, which had an IC of 2.13 μM, highlighting its potential as a therapeutic agent for breast cancer. Importantly, none of the tested compounds exhibited obvious toxicity toward MCF-10A human breast epithelial cells. Furthermore, compounds , , and were found to significantly inhibit the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells.