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Exploring the molecular mechanism of Epimedium for the treatment of ankylosing spondylitis based on network pharmacology, molecular docking, and molecular dynamics simulations

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Abstract

Ankylosing spondylitis (AS) is a rheumatic disease that causes inflammation and bone formation in the spine. Despite significant advances in treatment, adverse side effects have triggered research into natural compounds. Epimedium (EP) is a traditional Chinese herb with a variety of pharmacological activities, including antirheumatic, anti-inflammatory, and immunomodulatory activities; however, its direct effects on AS treatment and the underlying molecular mechanisms have not been systematically studied. Thus, here, we used network pharmacology, molecular docking, and molecular dynamics simulations to explore the targets of EP for treating AS. We constructed an interaction network to elucidate the complex relationship between EP and AS. Sixteen active ingredients in EP were screened; 80 potential targets were identified. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone, anhydroicaritin, and luteolin were the core components and TNF, IL-6, IL-1β, MMP9, and PTGS2 were the core targets. The GO and KEGG analyses indicated that EP may modulate multiple biological processes and pathways, including the AGE-RAGE, TNF, NF-κB/MAPK, and TLR signaling pathways, for AS treatment. Molecular docking and molecular dynamics simulations showed good affinity between the active components and core targets of EP, with stable binding within 100 nanoseconds. In particular, 8-(3-methylbut-2-enyl)-2-phenylchromone possessed the highest free energy of binding to PTGS2 and TNF (-115.575 and − 87.676 kcal/mol, respectively). Thus, EP may affect AS through multiple pathways, including the alleviation of inflammation, oxidative stress, and immune responses. In summary, we identified the active components and potential targets of EP, highlighting new strategies for the further experimental validation and exploration of lead compounds for treating AS.

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Data availability

No datasets were generated or analyzed during the current study. The original contributions presented in this study are included in the article/supplementary material, and further inquiries can be directed to the corresponding author. 

Abbreviations

MD:

Molecular dynamics

PPI:

Protein–protein interaction

GO:

Gene ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

MM-PBSA:

Molecular Mechanics Poisson-Boltzmann Surface Area

TNF:

Tumor necrosis factor

IL-6:

Interleukin 6

IL1β:

Interleukin 1β

MMP9:

Matrix metalloproteinase 9

PTGS2:

Prostaglandin G/H synthase 2

TGF-B1:

Transforming growth factor beta-1 proprotein

ESR1:

Estrogen receptor 1

RMSD:

Root mean square deviation

SASA:

Solvent accessible surface area

RMSF:

Root mean square fluctuation

OS:

Oxidative stress

COX-2:

Cyclooxygenase 2

PGE(2):

Prostaglandin E2

RAGE:

Receptor of advanced glycation end-products

PI3K-Akt:

Phosphatidilinositol 3-kinase/protein kinase B

NF-κB:

Nuclear factor-kappa B

MAPK:

Mitogen-activated protein kinase

TLRs:

Toll-like receptors

IBD:

Inflammatory bowel disease

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Funding

This research received support from the Department of Science and Technology of Sichuan Province, China (2023NSFSC1806, 2023NSFSC0679), and the National Famous Chinese Medicine Experts Inheritance Workshop Construction Project [(2022) No. 75].

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Authors and Affiliations

  1. School of Sports Medicine and Health, Chengdu Sports University, Chengdu, 610000, China

    Xiangjin Wang, Hao Wang, Langyu He, Yilang Hu, Zhaosen Li & Yuqin Zheng

  2. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, China

    Lijiao Wu & Maobin Yu

  3. Department of Respiratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, China

    Bo Peng

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Contributions

Methodology: XW and LW. Software: XW, LW, HW, and LH. Validation: XW and LW. Formal analysis: XW, YH, and ZL. Visualization: XW, LW, and MY. Conceptualization: BP, LW, and MY. Investigation: BP, YZ, YH, and ZL. Supervision: BP. Resources: LW, HW, and LH. Data Curation: LW, MY, and YZ. Writing—Original Draft: XW. Writing—Review & Editing: LW, MY, HW, LH, YH, ZL, YZ, and BP. Project administration: BP and LW. Funding acquisition: BP. All authors contributed to the article and approved the submitted version.

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Wang, X., Wu, L., Yu, M. et al. Exploring the molecular mechanism of Epimedium for the treatment of ankylosing spondylitis based on network pharmacology, molecular docking, and molecular dynamics simulations. Mol Divers (2024). https://doi.org/10.1007/s11030-024-10877-x

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