Abstract
This study aimed to investigate the potential molecular mechanism of BYHWD in treating epilepsy by regulating the adenosine system, based on network pharmacology, molecular docking, and molecular dynamics simulations. Active components of BYHWD and their targets were screened using databases such as TCMSP and SwissTargetPrediction. Epilepsy-related targets were obtained from GeneCards and OMIM. Compound-target networks and protein–protein interaction (PPI) networks were constructed. GO and KEGG enrichment analyses were performed. Molecular docking and molecular dynamics simulations were employed to validate the binding ability and stability of key components with adenosine receptors (ADORA1, ADORA2A). A total of 33 active components targeting adenosine receptors were screened, among which 13 components could simultaneously act on both ADORA1 and ADORA2A. Enrichment analysis suggested that the mechanism involves neuroactive ligand-receptor interaction, cAMP signaling pathway, and synaptic function regulation. Molecular docking showed that multiple components had high affinity for the receptors. Molecular dynamics simulations further confirmed the stable binding of isorhamnetin with ADORA2A, with a binding free energy of −26.51 kcal/mol. BYHWD exerts anti-epileptic effects by synergistically regulating adenosine receptors (ADORA1, ADORA2A) and their downstream signaling pathways through multiple active components, thereby restoring the excitatory/inhibitory balance of the neural network.
Data availability
All data generated or analysed during this study are included in this published article.
Abbreviations
- BYHWD:
-
Buyang Huanwu Decoction
- OB:
-
Oral bioavailability
- DL:
-
Drug-likeness
- PPI:
-
Protein–protein interaction
- GO:
-
Gene ontology
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- MD:
-
Molecular dynamics
- RMSD:
-
Root mean square deviation
- Rg:
-
Radius of gyration
- SASA:
-
Solvent accessible surface area
- RMSF:
-
Root mean square fluctuation
- MM/GBSA:
-
Molecular mechanics/Generalized born surface area
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Funding
The Undergraduate Innovation and Entrepreneurship Training Program of Guangzhou University of Chinese Medicine under Grant No. 202510572276.
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Wu Sitong: Conceptualization, Methodology, Writing—Original Draft, Writing—Review & Editing, Data Curation, Visualization, Formal Analysis, Software. Deng Yuhan: Conceptualization, Data Curation, Software. Yang Jiayue: Conceptualization, Data Curation. Peng Zhuoling: Conceptualization. Chen Jiatong: Conceptualization. All authors have read and agreed to the published version of the manuscript.
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This study is a computational analysis utilizing publicly available data and does not involve any human or animal experiments.
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Wu, S., Deng, Y., Yang, J. et al. A study on the mechanism of Buyang Huanwu Decoction in treating epilepsy by regulating adenosine levels. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41089-y
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DOI: https://doi.org/10.1038/s41598-026-41089-y
