文献类型：期刊文献

英文题名：Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer

作者：Li, Ling[1];Jin, Xiao-jie[1,2];Li, Jia-wei[1,3];Li, Cheng-hao[1];Zhou, Shuang-yan[4];Li, Jun-jie[1];Feng, Cai-qin[5];Liu, Dong-ling[1,2];Liu, Yong-qi[1,6]

第一作者：李莉;李琳;李丽

通信作者：Li, JW[1];Liu, YQ[1]

机构：[1]Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Coll Pharm, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Sch Basic Med Sci, Lanzhou, Peoples R China;[4]Chongqing Univ Posts & Telecommun, Chongqing Key Lab Big Data Bio Intelligence, Chongqing, Peoples R China;[5]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou, Peoples R China;[6]Gansu Univ Chinese Med, Minist Educ Peoples Republ China, Key Lab Dun Huang Med & Transformat, Lanzhou, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2021

卷号：112

期号：5

起止页码：1772

外文期刊名：CANCER SCIENCE

收录：;Scopus(收录号：2-s2.0-85102113221);WOS:【SCI-EXPANDED(收录号:WOS:000625889500001)】；

基金：Gansu University Key Laboratory for Molecular Medicine and Chinese Medicine Prevention and Treatment of Major Diseases, Gansu University of Chinese Medicine; National Natural Science

语种：英文

外文关键词：gastric cancer; Guiqi Baizhu prescription; molecular docking; molecular dynamics simulation; MST analysis; network pharmacology

摘要：Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K-AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1-ligand 1 (PD-L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD-L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD-L1, with K-d values of 3.7 mu mol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD-L1, calculated by molecular mechanics Poisson-Boltzmann surface area, of -26.55, -14.18, -19.41, and -11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN-45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.