Background: In recent years, diabetic foot has become a significant cause of disability and mortality among individuals with diabetes. With the progression of time and technology, both modern medicine and traditional Chinese medicine have gradually deepened their understanding and research into diabetic foot, further enhancing the treatment methods available for this condition. To a certain extent, this can alleviate patients' pain and improve their quality of life.
Objective: To explore the mechanism of Simiao Yong’an Decoction (SYD) in the treatment of diabetic foot (DF).
Methods: Databases and software such as TCMSP, GeneCards, OMIM, and TTD were used to identify the pharmacodynamic material basis, therapeutic targets, and metabolic pathways of SYD in the treatment of DF. The serum metabolomics of SYD was integrated with network pharmacology to validate the potential active components and metabolic pathways involved in SYD’s intervention in DF.
Results: The main active components of SYD in treating DF were found to be luteolin, quercetin, and formononetin. The treatment may act through targets such as AKT1, TNF, HSP90AA1, MAPK8, and STAT3, regulating pathways including the MAPK signaling pathway, TNF signaling pathway, phosphatidylinositol signaling pathway, HIF-1 signaling pathway, and Toll-like receptor signaling pathway. The phosphatidylinositol signaling pathway was consistent with the findings from serum metabolomics analysis of SYD.
Conclusion: The phosphatidylinositol signaling pathway may be a key metabolic pathway in the intervention of DF by SYD.
Declarations
Not applicable.
Authors' contributions
K. Zhang: Project leader, Project Research and development. B. Zhang: Network pharmacological analysis and paper writing. Q. Wu: Network pharmacological analysis, databases and software are TCMSP, geneCards, OMIM, and TTD. S. Zhu: Blood and urine samples were systematically collected from the participants. D. Wang: Systematic collection of blood metabolomics data. C. Zhang: Systematic collection of urine metabolomics data.
Ethics approval and consent to participate
The study was approved by the Ethics Committee of Heilongjiang Provincial Hospital (SYYLLBA2022037). All procedures involving human participants were conducted in accordance with the ethical standards set by the institutional and national research committees and with the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical standards. Informed consent was obtained from all participants before participation in the study.
Consent for publication
Not applicable.
Availability of data and materials
Not applicable.
Funding
This work was supported by the Traditional Chinese Medicine Scientific Research Project of Heilongjiang Provincial Administration of Traditional Chinese Medicine (Project No.: ZHY2022-066).
Declarations of Competing interests
The authors declare that they have no competing interests.
Acknowledgements
Not applicable.
Authors' other information
Not applicable.
| [1] |
Diabetes Foot Disease Branch of the China International Exchange and Promotion Association for Medical and Healthcare, Expert Committee on Diabetic Foot Disease of the China Branch of the International Vascular Union. Guidelines for diagnosis and treatment of diabetic foot in China. Chinese Journal for Clinicians, 2020; 48(1): 19-27.
|
| [2] |
Gan ZY, Li CN, Wei XL, et al. Progress in early diagnosis and treatment of diabetic peripheral neuropathy. China Health Stand Manag. 2023; 14(11):194-198.
|
| [3] |
Zhang K.X. Clinical and Metabolomic Study of Simiao Yong'an Decoction in the Treatment of Heat-Toxin Excess Type Diabetic Foot. Harbin: Heilongjiang University of Chinese Medicine, 2021.
|
| [4] |
Zhao Y, Wang LH, Liao HZ, et al. Mechanism of action of Simiao Yongan decoction in treatment of diabetic foot: a study based on network pharmacology and molecular docking. Hunan. J Tradit Chin Med. 2023; 39(8):166-173.
|
| [5] |
Han SL. Observation on curative effect of comprehensive external treatment of traditional Chinese medicine on diabetic foot ulcer stage. J Pract Tradit Chin Med. 2019; 35(5):612-613.
|
| [6] |
Jie SS, Liu JX, Yu Z, et al. Research progress on anti-inflammatory mechanism of Simiao Yongan decoction. J Basic Chin Med. 2022; 28(9):1539-1542.
|
| [7] |
Ru JL, Li P, Wang JN, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Chemin-. 2014; 6:13.
|
| [8] |
Consortium U. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res. 2021; 49(D1):D480-D489.
|
| [9] |
Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: the human gene integrator. Database. 2010;2010:baq020.
|
| [10] |
Amberger JS, Hamosh A. Searching online mendelian inheritance in man (OMIM): a knowledgebase of human genes and genetic phenotypes. Curr Protoc Bioinforma. 2017; 58 1.2.1-1.2.12.
|
| [11] |
Wang YX, Zhang S, Li FC, et al. Therapeutic target database 2020:enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res. 2020; 48(D1):D1031-D1041.
|
| [12] |
Szklarczyk D, Franceschini A, Wyder S, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015; 43(Database.):D447-D452.
|
| [13] |
Zhou YY, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019; 10(1):1523.
|
| [14] |
Burley SK, Berman HM, Kleywegt GJ, et al. Protein data bank (PDB): the single global macromolecular structure archive. Methods Mol Biol. 2017; 1607:627-641.
|
| [15] |
Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-2504.
|
| [16] |
Mao LS, Zhu XH. Application progress of network pharmacology in traditional Chinese medicine. J Tradit Chin Med Manag. 2021; 29(13):98-102.
|
| [17] |
Da CH, Pei GX. Network Pharmacology: A Rosetta Stone for Traditional Chinese Medicine. Drug Dev Res. 2015; 75(5):299-312.
|
| [18] |
Chang L, Graham PH, Ni J, et al. Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance. Crit Rev Oncol Hematol. 2015; 96(3):507-517.
|