Background: Arnebia euchroma (A. euchroma), a traditional Chinese medicine (TCM) for the treatment of blood diseases. In recent years, more and more researches have been conducted on the anti-tumor effect of shikonin and its derivatives, the major active components of A. euchroma. However, the underlying mechanism of action (MoA) for all the ingredients of A. euchroma on leukemia has not been explored systematically.
Methods: In this study, we tried to analyze the MoA of A. euchroma on leukemia via network pharmacology approach. Firstly, the chemical components and their concentrations in A. euchroma as well as leukemia-related targets were collected. Next, we predicted compound-target interactions (CTIs) via our balanced substructure-drug-target network-based inference (bSDTNBI) method. The known and predicted targets of A. euchroma and leukemia-related targets were merged together to construct A. euchroma-leukemia protein-protein interactions (PPIs) network. Then, weighted compound-target bipartite network was constructed according to combination of eight central attributes with concentrations information via Cytoscape. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets.
Results: A total of 65 components of A. euchroma were obtained and 27 of them with concentration information, which involved in 157 targets, 779 compound- target interactions (CTIs), including 129 known CTIs (KCTIs) and 650 predicted CTIs (PCTIs). Following the analysis of A. euchroma-leukemia PPI network, 37 targets were used to construct the weighted compound-target bipartite network and further KEGG pathway analysis. We found that A. euchroma candidate targets were significantly associated with several apoptosis and inflammation-related biological pathways, such as MAPK signaling pathway, PI3K-Akt signaling pathway, IL-17 signaling pathway, T cell receptor signaling pathway. Moreover, molecular docking simulation demonstrated that there were 8 pairs of PCTIs had the strong binding free energy.
Conclusions: This network pharmacology-based study considered the information of component concentration, in combination with molecular docking, deciphered that the efficacy of A. euchroma in the treatment of leukemia may be mainly attributed to 10 targets and 14 components, which were associated with inhibiting leukemia cell survival and inducing apoptosis, relieving inflammatory environment and inhibiting angiogenesis.