# Computational and Experimental Analysis of Sophora alopecuroides L. Chloroform Fraction: Active Components and Anti-Breast Cancer Resistance Mechanisms

## TL;DR

This study identifies active compounds in Sophora alopecuroides L. that reverse drug resistance in breast cancer and explains their mechanisms.

## Contribution

The study reveals a multi-component, multi-target, and multi-pathway mechanism of action for reversing breast cancer resistance.

## Key findings

- SaL-30, a chloroform derivative, showed strong toxicity against MCF-7/ADR cells with an IC50 of 8.941 µg/mL.
- SACG reverses resistance via the PI3K-AKT pathway and synergizes with Adriamycin (CI = 0.3258).
- Network pharmacology and molecular docking confirmed multi-component, multi-target, and multi-pathway interactions.

## 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 IC50 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.