Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.
Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.
复制标题
系统研究归芪白术治疗胃癌的有效成分及其作用机制。
DOI：
10.1111/cas.14851
复制
发表时间：
2021-05
期刊：
影响因子：
5.7
通讯作者：
Liu YQ
中科院分区：
文献类型：
--
作者：
Li L;Jin XJ;Li JW;Li CH;Zhou SY;Li JJ;Feng CQ;Liu DL;Liu YQ
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 μmol/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. We are committed to establishing a systematic research method based on network pharmacology, multitarget molecular docking, molecular dynamics simulation, and protein and experimental verification in vitro and in vivo, to establish a systematic analysis method for traditional Chinese medicine (TCM) treatment of diseases. We aim to provide a possible theoretical and experimental basis for the standardization and internationalization of TCM.
登录
查看更多内容
影响因子：
9.7
作者：
Chaganty BKR;Qiu S;Gest A;Lu Y;Ivan C;Calin GA;Weiner LM;Fan Z
通讯作者：
Fan Z
影响因子：
14.9
作者：
Kim S;Chen J;Cheng T;Gindulyte A;He J;He S;Li Q;Shoemaker BA;Thiessen PA;Yu B;Zaslavsky L;Zhang J;Bolton EE
通讯作者：
Bolton EE
影响因子：
5.6
作者：
Lee TS;Allen BK;Giese TJ;Guo Z;Li P;Lin C;McGee TD Jr;Pearlman DA;Radak BK;Tao Y;Tsai HC;Xu H;Sherman W;York DM
通讯作者：
York DM
影响因子：
5.6
作者：
Lan, Yin;Wang, Yi;Zeng, Qiutang
通讯作者：
Zeng, Qiutang
影响因子：
2.7
作者：
Elkamhawy, Ahmed;Farag, Ahmed Karam;Roh, Eun Joo
通讯作者：
Roh, Eun Joo