Abstract
Diabetic foot ulcer is a severe complication of diabetes, characterized by impaired wound healing and immune dysregulation. Although Astragalus membranaceus (AM) has been widely used and reported to exert beneficial effects in diabetic complications, its underlying mechanisms of action in DFU remain incompletely understood. This study integrated single-cell RNA sequencing (scRNA-seq) data from a public bioinformatic cohort (GSE245703; 4 non-diabetic foot ulcer (NFU) and 5 diabetic foot ulcer (DFU) samples) with network pharmacology to explore potential molecular mechanisms by which AM may be involved in DFU pathology. scRNA-seq analysis identified ten major cell types within the DFU microenvironment and revealed significant macrophage heterogeneity. Network pharmacology identified 14 active compounds in AM and their predicted targets, some of which overlapped with macrophage-associated differentially expressed genes. Molecular docking suggested strong binding affinities between selected AM compounds and macrophage-associated hub genes. qPCR validation in a clinical cohort (6 NFU and 9 DFU patients) confirmed differential expression of several candidate hub genes overlapping with predicted AM targets. Collectively, these results provide a single-cell–resolved, systems-level framework that links AM components to macrophage-associated molecular processes in DFU, offering a hypothesis-generating basis for future functional and translational studies.
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Data availability
The scRNA-seq data used in this study were obtained from the Gene Expression Omnibus database under accession number GSE245703 and are available at the following URL: https://identifiers.org/geo: GSE245703.
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Funding
This study was supported by the Yunnan Provincial Science and Technology Department (202301BE070001-039), and the Project for Establishing a Flagship Department of Integrated Chinese and Western Medicine.
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X.L. conceived and designed the study, performed data analysis, and drafted the manuscript. C.H. and Y.D. contributed to methodology and validation. G.Z. and N.C. supervised the study and revised the manuscript. Y.N., Y.L. and R.Z. collected samples. N.C. and Y.Y. ainistered the project and provided resources. All authors read and approved the final manuscript.
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Informed consent was obtained from all subjects involved in the study.
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The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Anning First People’s Hospital (Approval No: Lun Shen 2025-026 (Other)-01).
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Li, X., Dong, Y., Huang, C. et al. Mechanism of action of Astragalus membranaceus for treating diabetic foot ulcers based on single-cell RNA sequencing data and network pharmacology. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41921-5
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DOI: https://doi.org/10.1038/s41598-026-41921-5
