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

<i>Euphorbia ebracteolata</i> 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 <i>E. ebracteolata</i> 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 <i>E. ebracteolata</i> 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.