A Network Pharmacology Analysis of Cytotoxic Triterpenes Isolated fromEuphorbia abyssinicaLatex Supported by Drug-likeness and ADMET Studies

Abstract

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.

Network pharmacology and molecular docking study for biological pathway detection of cytotoxicity of the yellow jasmine flowers

“…The obtained protein interaction data was imported into the Cytoscape 3.9.1 application to generate a PPI protein interaction network. The CytoHubba plug-in was employed for the identification of Hub genes [ 23 ]. The cyto hubba plg-in has 12 topological features among which we used the “Degree” parameters to screen out the top-ranked proteins according to their degree value of interaction.…”

Apium extract alleviates indomethacin-induced gastric ulcers in rats via modulating the VEGF and IK-κB/NF-κB p65 signaling pathway: insights from in silico and in vivo investigations

“…A compounds-genes network was constructed based on chemical data informations obtained for each compound from the PubChem database ( https://pubchem.ncbi.nlm.nih.gov/ ) [ 56 ] (last accessed on 03–05-2023) and Swiss Target Prediction database: http://www.swisstargetprediction.ch/result.php?job=215444691&organism=Homo_sapiens [ 57 ] (last accessed on 03–05-2023) was used to find out the targets of each identified compound related to the human species (Homosapien) was selected and the top targets were chosen in the Swiss Target Prediction database with a probability score > 0.…”

In Vitro and Randomized Controlled Clinical Study of Natural Constituents’ Anti-HPV Potential for Treatment of Plantar Warts Supported with In Silico Studies and Network Analysis

“…For the construction of these networks, chemical data were obtained for each compound from the PubChem database ( ) [ 73 ] (last accessed on 24 February 2023), and the Swiss Target Prediction database ( ) [ 74 ] (last accessed on 28 February 2023) was used to find out the targets of each identified compound from Musca accuminata , Moringa olifera , and Nigella sativa related to the human species ( Homosapien ). We selected the top targets that were chosen in the Swiss Target Prediction database with a probability score > 0.…”

“…For the construction of these networks, chemical data were obtained for each compound from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/) [73] (last accessed on 24 February 2023), and the Swiss Target Prediction database (http://www. swisstargetprediction.ch/result.php?job=215444691&organism=Homo_sapiens) [74] (last accessed on 28 February 2023) was used to find out the targets of each identified compound from Musca accuminata, Moringa olifera, and Nigella sativa related to the human species (Homosapien).…”