Nowadays, cancer is considered one of the leading causes of death in developing countries. Due to mediocre socioeconomic status of many of the North African countries, people resort to traditional medicine from natural products for cancer therapy which are of great chemical complexity, interacting with several protein targets leading to synergistic effects. A holistic network pharmacology approach is needed for understanding the molecular mechanism of North African plants constituents in the different cancer-related pathways.The aim of this study is the implementation of network pharmacology for identification of the main active constituents of North African plants against cancer molecular targets and to explore their therapeutic mechanism.Constituents of North African plants were retrieved from public database and ADME screening was implemented for filtration of constituents using Qikprop software. STITCH database was used for predicting the plant constituents target proteins/genes, TDD DB and Uniprot databases were used for identifying genes related to cancer. Constituent-target gene (C-T), constituent-pathway (C-P) and plant-constituent-target gene (P-C-T) networks were constructed using Cytoscape to decipher the anti-cancer mechanism of action of the plants. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to cancer.6844 constituent were subjected to ADME filtration resulting in 3194 constituent which were forwarded to target prediction. 53 constituents and 36 targets were linked through 329 edges which constituted the main pathways related to cancer. Luteolin, alternariol, apigenin, aloe-emodin and myricetin had the highest combined score in the C-T network, while the genes CASP3, CYP1A1, CYP1B1, PTGS2, MAPK8, AKT1 and EGFR were the most enriched by the constituents in this network. Euphorbia spp., Hyphaene thebaica, Artemisia herba-alba, bee propolis and Marrubium vulgare possessed the largest number of P-C-T interactions. The identified targets were mainly associated with cell cycle arrest and apoptosis in addition to inhibition of cellular proliferation by revealing a striking functional association with various signal and cancer related pathways CONCLUSIONS: Analysis of the constructed pharmacological networks results allowed for the prediction and interpretation of the multi-constituent, multi-target, and multi-pathway mechanisms of North African plants as potential source for supportive treatment of cancer where their potential molecular mechanism towards cancer-associated targets, biological processes and pathways were revealed.
