Anti-colorectal cancer of Ardisia gigantifolia Stapf. and targets prediction via network pharmacology and molecular docking study.
Anti-colorectal cancer of Ardisia gigantifolia Stapf. and targets prediction via network pharmacology and molecular docking study.
复制标题
DOI：
10.1186/s12906-022-03822-8
复制
发表时间：
2023-01-09
影响因子：
3.9
通讯作者：
Hu, Xianjing
中科院分区：
文献类型：
--
作者：
Dai, Weibo;Yang, Jing;Liu, Xin;Mei, Quanxi;Peng, Weijie;Hu, Xianjing
关键词：
大叶紫荆（AGS）是一种广泛生长在中国南方的民间药物，几项研究报道了AGS可以抑制乳腺癌、肝癌和膀胱癌细胞系的增殖。然而，人们对其抗结直肠癌（CRC）的功效知之甚少。本研究采用MTT法、网络药理学分析、生物信息学、分子对接、分子动力学模拟等方法，探讨AGS抗结直肠癌的有效成分、靶点及可能的作用机制。MTT实验显示，正丁醇提取物（NBAGS）、乙酸乙酯提取物（EAAGS）和石油醚提取物（PEAGS） 3种组分对结直肠癌细胞的增殖均有显著抑制作用，其对HCT116细胞的IC50值分别为197.24、264.85、15.45µg/mL，对SW620细胞的IC50值分别为523.6、323.59、150.31µg/mL。鉴定出11- o-没食子酸根茎素、11- o-原儿茶根茎酸根茎素、11- o-丁香根茎酸根茎素、皂荚素B、根茎素、表儿茶素-3-没食子酸酯、没食子酸、槲皮素、豆甾醇、豆甾醇-3-o-β- d -葡萄糖吡喃苷等11种有效成分。通过数据库检索，共筛选出173个与生物活性成分相关的靶点和21572个与CRC相关的靶点。基于AGS与CRC的交叉靶点，利用String数据库构建蛋白-蛋白互作网络，从中得出核心靶点为SRC、MAPK1、ESR1、HSP90AA1、MAPK8。此外，GO分析显示AGS抗CRC的生物学过程、细胞成分和分子功能的数量分别为1079条、44条和132条，KEGG通路富集表明，AGS抗CRC可能共有96条信号通路参与，其中MAPK信号通路、脂质、动脉粥样硬化、癌症蛋白聚糖、前列腺癌、粘附体连接可能是主要通路。对接研究证实，AGS具有多成分、多靶点的抗CRC作用。分子动力学（MD）模拟分析表明，通过形成氢键，这种结合是稳定的。我们的研究表明，AGS具有良好的抗crc效力，具有多成分、多靶点、多信号通路的特点。在线版本包含补充资料，下载地址：10.1186/s12906-022-03822-8。
Ardisia gigantifolia Stapf. (AGS), a Chinese folk medicine widely grows in the south of China and several studies reported that AGS could inhibit the proliferation of breast cancer, liver cancer, and bladder cancer cell lines. However, little is known about its anti-colorectal cancer (CRC) efficiency. In the present study, a combination of MTT assay, network pharmacological analysis, bioinformatics, molecular docking, and molecular dynamics simulation study was used to investigate the active ingredients, and targets of AGS against CRC, as well as the potential mechanism. MTT assay showed that three kinds of fractions from AGS, including the n-butanol extract (NBAGS), ethyl acetate fraction (EAAGS), and petroleum ether fraction (PEAGS) significantly inhibited the proliferation of CRC cells, with the IC50 values of 197.24, 264.85, 15.45 µg/mL on HCT116 cells, and 523.6, 323.59, 150.31 µg/mL on SW620 cells, respectively. Eleven active ingredients, including, 11-O-galloylbergenin, 11-O-protocatechuoylbergenin, 11-O-syringylbergenin, ardisiacrispin B, bergenin, epicatechin-3-gallate, gallic acid, quercetin, stigmasterol, stigmasterol-3-o-β-D-glucopyranoside were identified. A total of 173 targets related to the bioactive components and 21,572 targets related to CRC were picked out through database searching. Based on the crossover targets of AGS and CRC, a protein-protein interaction network was built up by the String database, from which it was concluded that the core targets would be SRC, MAPK1, ESR1, HSP90AA1, MAPK8. Besides, GO analysis showed that the numbers of biological process, cellular component, and molecular function of AGS against CRC were 1079, 44, and 132, respectively, and KEGG pathway enrichment indicated that 96 signaling pathways in all would probably be involved in AGS against CRC, among which MAPK signaling pathway, lipid, and atherosclerosis, proteoglycans in cancer, prostate cancer, adherens junction would probably be the major pathways. The docking study verified that AGS had multiple ingredients and multiple targets against CRC. Molecular dynamics (MD) simulation analysis showed that the binding would be stable via forming hydrogen bonds. Our study showed that AGS had good anti-CRC potency with the characteristics of multi-ingredients, -targets, and -signaling pathways. The online version contains supplementary material available at 10.1186/s12906-022-03822-8.
登录
查看更多内容
DOI：
10.1016/j.pnpbp.2013.03.005
发表时间：
2013-07-01
影响因子：
5.6
作者：
Calati, Raffaella;Crisafulli, Concetta;Mendlewicz, Julien
通讯作者：
Mendlewicz, Julien
影响因子：
6.3
作者：
Genheden S;Ryde U
通讯作者：
Ryde U
影响因子：
24.5
作者：
Coker, Olabisi Oluwabukola;Nakatsu, Geicho;Yu, Jun
通讯作者：
Yu, Jun
评估 MM/PBSA 和 MM/GBSA 方法的性能。
影响因子：
5.6
作者：
Hou, Tingjun;Wang, Junmei;Li, Youyong;Wang, Wei
通讯作者：
Wang, Wei
影响因子：
4.6
作者：
Garcia-Rodriguez S;Callejas-Rubio JL;Ortego-Centeno N;Zumaquero E;Ríos-Fernandez R;Arias-Santiago S;Navarro P;Sancho J;Zubiaur M
通讯作者：
Zubiaur M