Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
Department of Endocrinology, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
Front Endocrinol (Lausanne). 2023 Oct 4;14:1236549. doi: 10.3389/fendo.2023.1236549. eCollection 2023.
To promote the development and therapeutic application of new medications, it is crucial to conduct a thorough investigation into the mechanism by which the traditional Chinese herb pair of Haizao-Kunbu (HK) treats Graves' disease (GD).
Chemical ingredients of HK, putative target genes, and GD-associated genes were retrieved from online public databases. Using Cytoscape 3.9.1, a compound-gene target network was established to explore the association between prosperous ingredients and targets. STRING, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analyses visualized core targets and disease pathways. Additionally, we conducted a refined analysis of the binding interactions between active ingredients and their respective targets. To visualize these findings, we employed precise molecular docking techniques. Furthermore, we carried out molecular dynamics simulations to gain insights into the formation of more tightly bound complexes.
We found that there were nine key active ingredients in HK, which mainly acted on 21 targets. These targets primarily regulated several biological processes such as cell population proliferation, protein phosphorylation, and regulation of kinase activity, and acted on PI3K-AKT and MAPK pathways to treat GD. Analysis of the molecular interaction simulation under computer technology revealed that the key targets exhibited strong binding activity to active ingredients, and Fucosterol-AKT1 and Isofucosterol-AKT1 complexes were highly stable in humans.
This study demonstrates that HK exerts therapeutic effects on GD in a multi-component, multi-target, and multi-pathway manner by regulating cell proliferation, differentiation, inflammation, and immunomodulatory-related targets. This study provides a theoretical foundation for further investigation into GD.
为了促进新药的开发和治疗应用，深入研究中药海藻昆布（HK）治疗格雷夫斯病（GD）的作用机制至关重要。
从在线公共数据库中检索 HK 的化学成分、假定靶基因和与 GD 相关的基因。使用 Cytoscape 3.9.1 构建化合物-基因靶标网络，以探讨丰富成分与靶标之间的关联。STRING、基因本体论和京都基因与基因组百科全书通路分析可视化核心靶标和疾病通路。此外，我们对活性成分与其各自靶标之间的结合相互作用进行了精细分析。为了可视化这些发现，我们采用了精确的分子对接技术。此外，我们进行了分子动力学模拟，以深入了解形成更紧密结合复合物的过程。
我们发现 HK 中有九种关键的活性成分，主要作用于 21 个靶标。这些靶标主要调节细胞群体增殖、蛋白磷酸化和激酶活性调节等几种生物学过程，并通过 PI3K-AKT 和 MAPK 通路作用于 GD。计算机技术下的分子相互作用模拟分析表明，关键靶标对活性成分表现出强烈的结合活性，并且在人类中 Fucosterol-AKT1 和 Isofucosterol-AKT1 复合物非常稳定。
本研究表明，HK 通过调节与细胞增殖、分化、炎症和免疫调节相关的靶标，以多成分、多靶标和多途径的方式对 GD 发挥治疗作用。本研究为进一步研究 GD 提供了理论基础。
