Abstract
We discovered that the chloroform extracted from Sophora alopecuroides L. exhibited the capacity to counteract multidrug resistance in breast cancer significantly. However, the precise active ingredients and their underlying mechanisms of action remain to be elucidated, necessitating the urgent undertaking of in-depth studies. In this study, an extract of Sophora alopecuroides L. was obtained through ethanol extraction and chloroform solvent extraction. Subsequent isolation and multi-round screening using MCF-7/ADR cells yielded the highly active chloroform derivative SaL-30. The active compound group of Sophora alopecuroides L. (SACG), consisting of 13 compounds, was confirmed by HPLC-QTOF-MS/MS and compositional screening. Network pharmacological analysis and molecular docking technology demonstrated that SACG reversed breast cancer resistance through an intricate multi-component (flavonoids/alkaloids), multi-target (AKT1/TNF/CDK2), and multi-pathway (PI3K-AKT/FoxO/MAPK) synergistic mode of action, with the PI3K-AKT pathway acting as the core regulator. Cell experiments further demonstrate that SaL-30 has strong toxicity against MCF-7/ADR by cellular assay, with an IC(50) value of 8.941 ± 0.327 µg/mL and a synergistic index of CI = 0.3258, exhibiting a strong synergistic anti-breast cancer effect when co-administered with Adriamycin. These findings provide a theoretical foundation for elucidating the anti-drug resistance mechanism of Sophora alopecuroides L.