Therapeutic Targets and Mechanism of Banxia Xiexin Decoction on Precancerous Lesions of Gastric Cancer: Network pharmacology

Guoxiu Zu, Ke-yi Sun, Ling Li, Xiu-song Zu, T. Han, Hai-liang Huang
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引用次数: 1

Abstract

BackgroundPrecancerous Lesions of Gastric Cancer (PLGC) is a common gastrointestinal tract and digestive systemdisease that lacks effective therapeutic drugs with good curative effects and few adverse reactions. Traditional Chinese medicine (TCM) has the advantages of multiple components, multiple channels, and fewer adverse reactions in the treatment of PLGC. Although Banxia xiexin Decoction (BXD) demonstrates a good therapeutic effect on PLGC, the pharmacological mechanism underlying its anticancer effect is still unclear. MethodsWe used a network pharmacology strategy, including the construction and analysis of a complex drug-disease network, to explore the complex mechanism of BXD treatment of PLGC. In addition, molecular docking technology was used to preliminarily study the binding ability of the potential active components and core therapeutic targets of BXD. ResultsThe networkpharmacology results showed 80 targets of BXD that are involved in PLGC. PPI network analysis demonstrated that the top10 core targets were JUN, TP53, MAPK3, MAPK1, TNF, VEGFA, MAPK14, ESR1, NR3C1, and MAPK8. The GO enrichment analysis results showed that the BXD anti-cancer and anti-inflammatory mechanism mainly involves cellular response to organic cyclic compound, response to toxic substance, response to oxidative stress, cellular response to nitrogen compound, response to inorganic substance, and others. The KEGG analysis results indicated that BXD may regulate 167 pathways such as MAPK signaling pathway and pathway in cancer in the treatment of PLGC. The molecular docking resultsshowed that the binding energies of beta sitosterol withMAPK1, MAPK3, MAPK14, JUN, and VEGFA were less than−7.0 kcal·mol−1, indicating a good docking effect. ConclusionsThis study reflects the characteristics of the mechanism of action by which BXD treats PLGC, which includes multiple components, multiple targets, and multiple pathways, and provides a biological basis for further verification and a novel perspective for drug discoveryin PLGC.
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半夏泻心汤治疗胃癌癌前病变的靶点及机制:网络药理学
背景胃癌癌前病变(PLGC)是一种常见的胃肠道和消化系统疾病,缺乏有效的治疗药物,疗效好,不良反应少。中药治疗PLGC具有多成分、多渠道、不良反应少的优势。半夏泻心汤对PLGC有较好的治疗效果,但其抗癌作用的药理机制尚不清楚。方法采用网络药理学策略,构建复杂的药物-疾病网络,探讨BXD治疗PLGC的复杂机制。此外,利用分子对接技术,初步研究了BXD潜在活性成分与核心治疗靶点的结合能力。结果网络药理学结果显示,BXD的80个靶点参与了PLGC。PPI网络分析显示,top10核心靶点分别为JUN、TP53、MAPK3、MAPK1、TNF、VEGFA、MAPK14、ESR1、NR3C1和MAPK8。氧化石墨烯富集分析结果显示,BXD的抗癌抗炎机制主要涉及细胞对有机环化合物的应答、对有毒物质的应答、对氧化应激的应答、对氮化合物的应答、对无机物的应答等。KEGG分析结果表明,BXD在PLGC治疗中可能调控MAPK信号通路、肿瘤通路等167条通路。分子对接结果表明,β谷甾醇与mapk1、MAPK3、MAPK14、JUN和VEGFA的结合能均小于−7.0 kcal·mol−1,对接效果良好。结论本研究反映了BXD治疗PLGC多组分、多靶点、多通路的作用机制特点,为进一步验证PLGC提供了生物学基础,并为PLGC的药物发现提供了新的视角。
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