Exploration of Euscaphic Acid on Non-Hodgkin Lymphoma Based on Network Pharmacology, Molecular Docking and Cell Experiment

Abstract

Background: Euscaphic acid (EA) has been found that can inhibit the proliferation of various types of tumor cells, including non-Hodgkin's lymphoma (NHL) cells. However, the underlying mechanism of EA in the treatment of NHL is unclear. Objective: To study the pharmacological mechanism and experimental verification of EA in the treatment of NHL by network pharmacology method and cell experiments. Methods: Firstly, we screened EA-related targets and NHL-related targets from public databases to obtain the common targets shared between EA and NHL. Secondly, network pharmacology constructing and enrichment analyses were applied to predict the underlying biological function and mechanism involved in the anti-NHL effect of EA. Following this, molecular docking and molecular dynamic simulation were conducted to verify the reliability of the interactions between potential targets and compounds. Furthermore, a series of experiments were carried out in vitro to further validate the results. Results: A total of 121 compound targets and 2341 disease targets were identified, resulting in 51 EA anti-NHL targets. Network analysis highlighted 8 core target genes，which probably played an important role in the treatment of EA in NHL. Enrichment analysis showed that EA acted on NHL through multiple pathways, especially pathways in cancer, inducing apoptosis and inhibiting cell cycle. The molecular docking results show strong interaction between the core targets and the EA. Notably, EA binds stably to IGF1R, a finding that was further validated through molecular dynamics simulations. Cell experiments verified EA inhibited the proliferation of RAJI cells, and induced cell apoptosis. In addition, EA inhibits the expression of IGF1R. Conclusions: We have verified the potential mechanism of action of Euscaphic acid on NHL by network pharmacology combined with molecular docking and molecular dynamics simulation, and vitro experiments show that EA is a promising drug for the treatment of NHL.