Possible molecular exploration of herbal pair Haizao-Kunbu in the treatment of Graves' disease by network pharmacology, molecular docking, and molecular dynamic analysis

Mengfei Yang; Yiwen Lai; Di Gan; Qingyang Liu; Yingna Wang; Xinyong He; Yi An; Tianshu Gao

doi:10.3389/fendo.2023.1236549

Possible molecular exploration of herbal pair Haizao-Kunbu in the treatment of Graves' disease by network pharmacology, molecular docking, and molecular dynamic analysis

Front Endocrinol (Lausanne). 2023 Oct 4:14:1236549. doi: 10.3389/fendo.2023.1236549. eCollection 2023.

Authors

Mengfei Yang¹, Yiwen Lai², Di Gan¹, Qingyang Liu², Yingna Wang², Xinyong He³, Yi An⁴, Tianshu Gao²

Affiliations

¹ Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
² Department of Endocrinology, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
³ Insititute of Laboratory Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
⁴ Department of Obstetrics, The People's Hospital of Liaoning, Shenyang, Liaoning, China.

Abstract

Objective: 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).

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Graves’ disease; Haizao-Kunbu; molecular docking; molecular dynamic analysis statements and declarations; network pharmacology.

MeSH terms

Graves Disease* / drug therapy
Graves Disease* / genetics
Humans
Molecular Docking Simulation
Molecular Dynamics Simulation*
Network Pharmacology
Phosphatidylinositol 3-Kinases

Substances

Phosphatidylinositol 3-Kinases

Grants and funding

This work was supported by the Foundation of Shenyang Bureau of Science and Technology [grant number 22-321-34-12].