网络药理学与计算验证揭示健脾化湿中药对抗胃癌的多靶点机制

Pharmacological Research - Modern Chinese Medicine Pub Date : 2025-06-25 DOI:10.1016/j.prmcm.2025.100648

Shuping Qiu , Zhe Jing , Rong Su , Xinhong Chen , Meiyan Zhu , Yuhong Wu , Jing Han , Hailong Li

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引用次数: 0

摘要

目的探讨以茯苓为代表的各种健脾祛湿中药对的相关性。大灰狼（斑鸠）Fr. Poria Cocos （Schw.）狼与Coicis精液，Polyporus umellatus （Pers.）利用网络药理学、分子对接、动态模拟等方法，对黄芩、枸杞、胃癌及其亚型进行了研究。方法从TCMSP中鉴定活性成分和靶点，并用SwissTargetPrediction进行补充。gc相关靶从GeneCards、OMIM和TTD中检索。使用Venny 2.1.0分析交叉点，使用STRING和Cytoscape 3.9.1构建PPI网络。通过DAVID和生物信息学网站进行GO和KEGG分析。使用Kaplan-Meier绘图仪进行Kaplan-Meier生存分析。使用CB-Dock2、AutoDock Vina1.5.6、PyMol、Discovery Studio 2019、GROMACS 2023、CHARMM 36、Ewald （PME）和Verlet进行分子对接和动力学模拟。结果分别鉴定出15、11、9、29、8种有效成分。常见靶点如IL6、TNF、BCL2和MMP9被认为是GC治疗的潜在关键靶点。GO和KEGG分析强调了通过STAT3/VEGF轴介导的磷酸化相关途径。Kaplan-Meier分析显示，TNF、MMP9、HIF1A、CASP3、AKT1、CCND1、ESR1、BCL2L1、MAPK1、TP53、MYC、PTGS2与胃癌患者的总生存率显著相关。分子对接和动力学模拟表明，IL6与木犀草素、TNF与猪孢酸C、BCL2与沃根素、MMP9与槲皮素具有良好的结合亲和力。结论健脾祛湿中药配用可能通过与关键靶点的相互作用调节信号通路，发挥抗炎、抗氧化、抗增殖、促凋亡等作用。这表明胃癌治疗具有治疗潜力。

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Network Pharmacology and Computational Validation Uncover the Multi-Target Mechanisms of Spleen-Strengthening and Dampness-resolving Herb pair against Gastric Cancer

Objective

This study investigates the correlation between various spleen-invigorating and dampness-removing herb pairs, including Poria Cocos (Schw.) Wolf with Polyporus Umbellatus (Pers.) Fr., Poria Cocos (Schw.) Wolf with Coicis Semen, Polyporus Umbellatus (Pers.) Fr. with Scutellariae Barbatae Herba, and Coicis Semen with Mume Fructus, and gastric cancer and its subtypes, utilizing network pharmacology, molecular docking, and dynamic simulations.

Methods

Active components and targets were identified from TCMSP and supplemented using SwissTargetPrediction. GC-related targets were retrieved from GeneCards, OMIM, and TTD. Intersections were analyzed with Venny 2.1.0, and PPI networks were constructed using STRING and Cytoscape 3.9.1. GO and KEGG analyses were conducted with DAVID and the Bioinformatics websites. Kaplan-Meier survival analysis was performed using the Kaplan-Meier Plotter. Molecular docking and dynamics simulations were carried out with CB-Dock2, AutoDock Vina1.5.6, PyMol, Discovery Studio 2019, GROMACS 2023, CHARMM 36, Ewald (PME), and Verlet.

Results

We identified 15, 11, 9, 29, and 8 active components in the respective herbs. Common targets such as IL6, TNF, BCL2, and MMP9 were recognized as potential key targets for GC treatment. GO and KEGG analyses highlighted phosphorylation-related pathways mediated through the STAT3/VEGF axis. Kaplan-Meier analysis indicated that TNF, MMP9, HIF1A, CASP3, AKT1, CCND1, ESR1, BCL2L1, MAPK1, TP53, MYC, and PTGS2 significantly correlated with the overall survival of GC patients. Molecular docking and dynamics simulations demonstrated favorable binding affinities between IL6 and luteolin, TNF and poricoic acid C, BCL2 and wogonin, and MMP9 and quercetin.

Conclusion

It is suggested that the pairing of herbs that are both spleen-invigorating and dampness-removing may exert anti-inflammatory, antioxidant, anti-proliferative, and pro-apoptotic effects by modulating signalling pathways through interactions with key targets. This suggests that there is therapeutic potential for GC treatment.

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来源期刊

Pharmacological Research - Modern Chinese Medicine

CiteScore

1.60

自引率

0.00%

发文量