基于计算机辅助药物设计及网络药理学探析复方补中益气汤对子宫内膜癌的作用机制研究

Network pharmacology-based prediction of the active ingredients and potential targets of Bu-Zong-Yi-Qi-Tang for the treatment of endometrial cancer

目的:通过网络药理学和计算机辅助药物设计,找出补中益气汤的潜能成分,并探讨其成为治疗子宫内膜癌的药物的可能性。方法:从DisGeNET和BisoGenet应用程序中收集与子宫内膜癌相关的基因和蛋白质以及从中医药数据库中收集复方中药补中益气汤的成分,运用Cytoscape建立网络关系图,并用CytoNCA筛选出能影响子宫内膜癌的蛋白质。再运用Surflex-Dock对补中益气汤的10种中草药的534个成分与子宫内膜癌相关的蛋白质进行柔性分子对接及分析其在活性位点的结合模式,并使用FAF-Drugs3和OSIRIS进行分子结构的筛选以预测其吸收、分布、代谢、排泄和毒性(ADMET)。结果:补中益气汤的六氢西红柿红素、八氢西红柿红素、新橙皮苷和橙皮苷这4个化合物与子宫内膜癌相关的蛋白质有好的结合亲和力与良好的药物特性。结论:从研究和文献中发现这4个化合物与癌症相关,有望进一步研究成为治疗子宫内膜癌的药物。

Objective： Bu-Zong-Yi-Qi-Tang demonstrated promising in vivo data in the inhibition of endometrial cancer ceils from vari- ous studies, however, the pharmacological mechanism is still unknown. Methods： Here, a computational network pharmacology ap- proach is constructed to predict the effects of 534 bioactive ingredients on the potential targets of endometrial cancer. This network was created using three cytoscape plugins, which are DisGeNET, BisoGenet and CytoNCA. Docking was performed using Surflex-Dock to calculate the binding affinities between the bioactive ingredients and the potential targets. FAF-Drugs3 and OSIRIS were used to screen the ingredients with adequate drug-like and ADMET properties. Results： Overall, phytofluene, phytoen, neohesperidin and hesperidin were predicted to be potential inhibitors with good pharmacokinetic properties and minimal adverse reactions. Conclusion： These com- pounds have the highest potential for further in vitro and in vivo investigation with the aim of developing safe and high-efficacy endo- metrial cancer treatment.