Luo Yu-Ting, Lin Long-Fei, Liu Yu-Ling, Shi Guo-Lin, Wu Yan-Qiu, Yang An-Hui, Li Hui
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China Jiangxi University of Traditional Chinese Medicine Nanchang 330004, China.
Zhongguo Zhong Yao Za Zhi. 2020 Dec;45(23):5753-5761. doi: 10.19540/j.cnki.cjcmm.20201026.401.
The aim of this paper was to explore the potential molecular mechanism of Banxia Xiexin Decoction in the treatment of colon cancer through pharmacology network and molecular docking methods. The chemical constituents and action targets of 7 herbs from Banxia Xiexin Decoction were collected by using TCMSP database,Chinese Pharmacopoeia and literatures consultation. GeneCards database was used to predict the potential targets of colon cancer. GO biological process analysis and KEGG pathway enrichment analysis of the disease and drug intersection targets were carried out through DAVID database. "Component-target-pathway" network and protein-protein interaction(PPI) network were construction by using Cytoscape and STRING database,and then the core components and targets of Banxia Xiexin Decoction in the treatment of colon cancer were selected according to the topological parameters. Finally, Autodock Vina was used to realize the molecular docking of core components and key targets. The prediction results showed that there were 190 active compounds and 324 corresponding targets for Banxia Xiexin Decoction,involving 74 potential targets for colon cancer. Cytoscape topology analysis revealed 11 key targets such as STAT3,TP53,AKT1,TNF,IL6 and SRC, as well as 10 core components such as quercetin,β-sitosterol,baicalein,berberine,and 6-gingerol.In bioinformatics enrichment analysis, 679 GO terms and 106 KEGG pathways were obtained, mainly involving PI3 K-AKT signaling pathway,TNF signaling pathway and TP53 signaling pathway. The results of molecular docking showed that baicalein,berberine,licochalcone A and 6-gingerol had a high affinity with SRC,STAT3,TNF and IL6. The results suggested that Banxia Xiexin Decoction could play an anti-colon cancer effect by inhibiting cell proliferation, regulating cell cycle, inducing apoptosis and anti-inflammatory function. The study revealed the multi-components,multi-targets and multi-pathways molecular mechanism of Banxia Xiexin Decoction,which could provide scientific basis and research ideas for the clinical application of Banxia Xiexin Decoction and the treatment of colon cancer with compound Chinese medicines.
本文旨在通过药理学网络和分子对接方法探索半夏泻心汤治疗结肠癌的潜在分子机制。利用中药系统药理学数据库与分析平台（TCMSP）数据库、《中国药典》并查阅文献，收集半夏泻心汤7味药材的化学成分及作用靶点。使用基因卡片（GeneCards）数据库预测结肠癌的潜在靶点。通过DAVID数据库对疾病与药物的交集靶点进行基因本体（GO）生物学过程分析和京都基因与基因组百科全书（KEGG）通路富集分析。利用Cytoscape软件和STRING数据库构建“成分-靶点-通路”网络和蛋白质-蛋白质相互作用（PPI）网络，然后根据拓扑参数筛选出半夏泻心汤治疗结肠癌的核心成分和靶点。最后，使用Autodock Vina软件实现核心成分与关键靶点的分子对接。预测结果显示，半夏泻心汤有190种活性化合物和324个相应靶点，涉及74个结肠癌潜在靶点。Cytoscape拓扑分析揭示了11个关键靶点，如信号转导和转录激活因子3（STAT3）、肿瘤蛋白p53（TP53）、蛋白激酶B（AKT1）、肿瘤坏死因子（TNF）、白细胞介素6（IL6）和原癌基因酪氨酸蛋白激酶（SRC），以及10个核心成分，如槲皮素、β-谷甾醇、黄芩素、小檗碱和6-姜酚。在生物信息学富集分析中，获得了679个GO术语和106条KEGG通路，主要涉及磷脂酰肌醇-3激酶（PI3K）-蛋白激酶B（AKT）信号通路、TNF信号通路和TP53信号通路。分子对接结果表明，黄芩素、小檗碱、甘草查尔酮A和6-姜酚与SRC、STAT3、TNF和IL6具有较高亲和力。结果表明，半夏泻心汤可能通过抑制细胞增殖、调节细胞周期、诱导凋亡和抗炎作用发挥抗结肠癌效应。本研究揭示了半夏泻心汤多成分、多靶点、多通路的分子机制，可为半夏泻心汤的临床应用及复方中药治疗结肠癌提供科学依据和研究思路。
