Study on Antitumor Secondary Metabolites from Euphorbia ebracteolata Hayata: Structural Characterization, Network Pharmacology, Molecular Docking and In Vitro

Euphorbia ebracteolata Hayata, a perennial herbaceous plant known as "langdu" in traditional Chinese medicine, utilizes its dried root for treating cancer, ascites, and edema. In this study, a structure-guided chemical investigation of E. ebracteolata led to the identification of 21 secondary metabolites. Notably, five of these were previously undescribed compounds, designated as euphebranones A–E, whose structures were elucidated through comprehensive spectroscopic analysis. Among these, euphebranones B–E were found to be unusual derivatives of ECBs. Given the traditional application of E. ebracteolata in cancer treatment, we screened these new compounds against a panel of tumor cell lines. Interestingly, (±)-euphebranone A, a racemic compound, demonstrated excellent antiproliferation activity against SMMC-7721 cells, with an IC50 value of 0.625 ± 0.039 μM. Mechanistic studies revealed that (±)-euphebranone A induced cell-cycle arrest in the G2/M phase and may inhibit the viability of hepatocellular carcinoma cells by suppressing the EGFR/PTEN and PI3K/AKT signaling pathways.