Network Pharmacology Analysis to Uncover the Potential Mechanisms of Lycium barbarum on Colorectal Cancer

Background: Studies have shown that extracts from Lycium barbarum exerted protective effects against colorectal cancer (CRC) cells. We used the network pharmacology method to determine the effects of L. barbarum on CRC and to predict core targets, biological functions, pathways, and mechanisms of action.

Method: We obtained the active compounds and their targets in L. barbarum via use of the Traditional Chinese Medicine System Pharmacology Database (TCMSP), gathered the CRC targets from Malacards, TTD, GeneCards, and DisGeNET, and chosen the overlapped targets as the candidate targets. After protein-protein interaction (PPI) network analysis, 20 with the highest node degree were selected as the core targets, and their enrichment and pathways were analyzed. Furthermore, we employed iGEMDOCK to validate the compound-target relation.

Result: Eventually, 103 overlapped targets were chosen as the candidate targets. Targets with the top 20 highest node degree were selected as the core targets. Gene Ontology (GO) enrichment analysis indicated that the core targets were enriched in cell proliferation regulation, extracellular space, cytokine receptor binding, and so on. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis proved that the core targets were significantly enriched in bladder cancer, pathways in cancer. The docking results demonstrated that beta-sitosterol, glycitein, and quercetin had good binding activity to CRC putative targets.

Conclusion: Our work successfully predicted the functioning ingredients and potential targets of L. barbarum in CRC and illustrated the potential pathways and mechanisms comprehensively. Nevertheless, these results still call for in vitro and in vivo experiments to validate.