A Network Pharmacology Analysis of Cytotoxic Triterpenes Isolated from Euphorbia abyssinica Latex Supported by Drug-likeness and ADMET Studies

[Image: see text] Euphorbia plants have been identified as potential sources of antitumor lead compounds. The current study aimed to isolate and identify the main active constituents of Euphorbia abyssinica latex followed by a cytotoxic evaluation. A network pharmacology approach was employed to predict the underlying mechanism. Finally, drug-likeness and ADMET studies were conducted for active compounds. The phytochemical investigation of the latex of E. abyssinica resulted in the isolation of two triterpenes, 3-acetyloxy-(3α)-urs-12-en-28-oic methyl ester (1) and lup-20(29)-en-3α,23-diol (2). The dichloromethane extract displayed potent cytotoxic activity against the MCF7 cell line with an IC(50) value of 4.27 ± 0.12 μg/mL but weak activity against HepG2 and HeLa cell lines (IC(50) = 20.47 ± 1.17 and 26.73 ± 2.99 μg/mL, respectively) compared to doxorubicin. Compound 1 showed an encouraging cytotoxic effect against MCF7 with IC(50) = 4.20 ± 0.20 μg/mL, followed by compound 2 (IC(50) = 5.8 ± 0.35 μg/mL). The network analysis revealed that the two isolated compounds are linked to 68 targets of human nature, among which 51 genes are linked to breast carcinomas and 5 targets (AR, CYP19A1, EGFR, PGR, and PTGS2) might be the top therapeutic targets of isolated compounds on breast cancer. Furthermore, the gene-enrichment analysis revealed that E. abyssinica could play a role in the treatment of breast cancer by striking 51 potential targets via mainly three signaling pathways: P13K–AKT, Wnt, and VEGF. Therefore, isolated triterpenes could be considered effective antitumor agents for breast cancer by elucidating their candidate target to alleviate breast cancer and related signaling pathways of the targets.