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基于网络药理学和分子对接的升仙汤抗肺腺癌生物活性成分及分子机制研究

Bioactive components and the molecular mechanism of Shengxian Decoction against lung adenocarcinoma based on network pharmacology and molecular docking.

作者信息

Yuan Ruijiao, Li Kejuan, Li Qi, Wang Chun, Zhang Hong, Ge Lihong, Ren Yifeng, You Fengming

机构信息

College of Life Science, Sichuan Normal University Chengdu, Sichuan, China.

Hospital of Chengdu University of Traditional Chinese Medicine Chengdu, Sichuan, China.

出版信息

Am J Transl Res. 2023 Dec 15;15(12):6988-7012. eCollection 2023.

Abstract

OBJECTIVE

The aim of this study was to identify the active components of Shengxian Decoction (SXT) and to elucidate the multi-component, multi-target, and multi-pathway regulatory mechanisms underlying the efficacy of SXT in treating lung adenocarcinoma (LUAD).

METHODS

The effects of SXT extract on proliferation, migration, and invasion capabilities of human LUAD cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, and Transwell assays. High-Performance Liquid Chromatography (HPLC) was employed to pinpoint the primary active constituents of SXT. The SXT-active component-target-pathway network and protein-protein interaction (PPI) network were constructed based on network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID. The clinical significance of key targets was assessed using several external databases, and molecular docking confirmed the binding affinities between key targets and SXT active components.

RESULTS

SXT significantly inhibited the proliferation, migration and invasion of human LUAD cells. HPLC identified and quantified seven active SXT components. Network pharmacology yielded 197 targets, 128 signaling pathways, and 448 GO terms. The PPI network and external validation underscored 13 key targets significantly associated with the influence of SXT on LUAD progression. Molecular docking demonstrated strong interactions between SXT active components and key targets.

CONCLUSION

SXT treats LUAD through a multifaceted approach involving various components, targets, and pathways. This research offers novel insights into the constituents and molecular mechanisms of SXT in LUAD therapy.

摘要

目的

本研究旨在确定升仙汤(SXT)的活性成分,并阐明SXT治疗肺腺癌(LUAD)疗效背后的多成分、多靶点和多途径调控机制。

方法

通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)、伤口愈合和Transwell实验,测定SXT提取物对人LUAD细胞增殖、迁移和侵袭能力的影响。采用高效液相色谱法(HPLC)确定SXT的主要活性成分。基于网络药理学构建SXT活性成分-靶点-途径网络和蛋白质-蛋白质相互作用(PPI)网络。使用DAVID进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径分析。利用多个外部数据库评估关键靶点的临床意义,分子对接证实关键靶点与SXT活性成分之间的结合亲和力。

结果

SXT显著抑制人LUAD细胞的增殖、迁移和侵袭。HPLC鉴定并定量了七种SXT活性成分。网络药理学得出197个靶点、128条信号通路和448个GO术语。PPI网络和外部验证强调了13个与SXT对LUAD进展影响显著相关的关键靶点。分子对接表明SXT活性成分与关键靶点之间有强烈的相互作用。

结论

SXT通过涉及多种成分、靶点和途径的多方面方法治疗LUAD。本研究为SXT在LUAD治疗中的成分和分子机制提供了新的见解。

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