Network Pharmacology and Experimental Verification: SanQi-DanShen Treats Coronary Heart Disease by Inhibiting the PI3K/AKT Signaling Pathway.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S480248

Min Zhao, Liuxiang Feng, Wenhua Li

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引用次数: 0

Abstract

Objective: To employee network pharmacology to predict the components and pathways of SanQi-DanShen (SQDS) in treating coronary heart disease, followed by in vitro experiments to validate the molecular mechanism of SQDS in treating coronary heart disease.

Methods: We sourced the active ingredients and targets of Panax notoginseng and Danshen from the Traditional Chinese Medicine Systems Pharmacology database. Coronary heart disease related genes were retrieved from the OMIM, Genecards, and Therapeutic Target databases. Using Cytoscape 3.7.2 software, we constructed a network diagram illustrating the components and targets of SQDS. The associated targets were then imported into the STRING database to build a protein-protein interaction network. The Metascape database and WeChat software were utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Lastly, we performed molecular docking between the key components and related targets using AutoDock Vina. To validate the potential mechanism of SQDS in treating coronary heart disease, we established an acute coronary heart disease rat model via tail vein injection of pituitrin.

Results: Network pharmacology analysis revealed that 65 active ingredients and 167 targets of SQDS are implicated in the treatment of coronary heart disease. The key targets identified include AKT1, TNF, TP53, IL6, and VEGFA. Notably, the PI3K/AKT signaling pathway emerged as the primary pathway. Furthermore, animal experiments showed that, compared to the model group, SQDS significantly reduced levels of TNF-α, IL-6, Bax, and cardiac troponin I, while increasing Bcl-2 content. It also notably suppressed the expression of p-PI3K and p-AKT, thereby offering protection to myocardial tissue.

Conclusion: Through the integrated approach of network pharmacology and molecular docking, we have established that SQDS exerts a multi-component, multi-target, and multi-pathway synergistic therapeutic effect on coronary heart disease. Its mechanism may involve the inhibition of the PI3K/AKT signaling pathway and the reduction of inflammatory factor expression.

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网络药理学与实验验证：三七丹参通过抑制 PI3K/AKT 信号通路治疗冠心病

目的利用网络药理学预测三七丹参治疗冠心病的成分和途径，并通过体外实验验证三七丹参治疗冠心病的分子机制：方法：我们从中药系统药理学数据库中获取了三七和丹参的有效成分和靶点。冠心病相关基因来自 OMIM、Genecards 和 Therapeutic Target 数据库。我们使用 Cytoscape 3.7.2 软件构建了一个网络图，说明了 SQDS 的组成和靶标。然后将相关靶标导入 STRING 数据库，构建蛋白质-蛋白质相互作用网络。我们利用 Metascape 数据库和微信软件进行了基因本体和京都基因和基因组百科全书的富集分析。最后，我们使用 AutoDock Vina 在关键成分和相关靶标之间进行了分子对接。为了验证 SQDS 治疗冠心病的潜在机制，我们通过尾静脉注射垂体促肾上腺皮质激素建立了急性冠心病大鼠模型：网络药理学分析表明，SQDS 的 65 种活性成分和 167 个靶点与冠心病的治疗有关。发现的关键靶点包括 AKT1、TNF、TP53、IL6 和 VEGFA。值得注意的是，PI3K/AKT 信号通路成为主要通路。此外，动物实验表明，与模型组相比，SQDS 能显著降低 TNF-α、IL-6、Bax 和心肌肌钙蛋白 I 的水平，同时增加 Bcl-2 的含量。它还能明显抑制 p-PI3K 和 p-AKT 的表达，从而为心肌组织提供保护：通过网络药理学和分子对接的综合方法，我们确定了 SQDS 对冠心病具有多成分、多靶点、多途径的协同治疗作用。其机制可能包括抑制 PI3K/AKT 信号通路和减少炎症因子的表达。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.