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Network pharmacology-based approach for exploring the biotargets and mechanisms of vitamin A for the treatment of diabetic foot ulcers
doi: 10.2478/fzm-2023-0023
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Abstract:
Background In some developing countries, people have little knowledge about the causes of diabetic foot ulcers. Therefore, public health education for patients on these conditions is a prerequisite for effective pharmacological treatment. Diabetic foot ulcers are a complex symptom of diabetes and are hard to cure due to the lack of efficacious medicine and alternative treatment approaches. Vitamin A (VA) is known to have potent biological functions, including skin repair and immunoregulation. However, the potential pharmacological effects and molecular mechanisms of VA on foot ulcers are still to be discovered. Methods By using bioinformatic/computational analyses, including network pharmacology, gene ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we aimed to identify and reveal the pharmacological targets, molecular mechanisms, biological functions, and signaling pathways of VA in the treatment of diabetic foot ulcers. Results A total of 66 intersection genes were identified as candidate targets of VA, which are related to diabetic foot ulcers. Therein, 18 core genes/targets, namely JUN, MAPK1, THRB, MAPK14, MTNR1B, CXCR3, ESR1, AR, HDAC1, IL-10, CNR1, DRD2, EGFR, ADRA2A, CCND1, RXRB, RARA , and RXRA , were further identified. Furthermore, the biological processes, cell components, and molecular functions which may underlie the effects of VA against diabetic foot ulcers were characterized. Conclusion Based on our findings, we concluded that the pharmacological effects of VA on diabetic foot ulcers primarily involve the promotion of cellular regeneration and proliferation and the inhibition of inflammatory response. The core genes/targets may potentially serve as promising biomarkers for the diagnosis of diabetic foot ulcers. -
Key words:
- diabetic foot ulcers /
- vitamin A /
- network pharmacology /
- core genes /
- mechanisms
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Figure 1. Flowcharts illustrating the network pharmacology approaches and procedures used in the present study to reveal the therapeutic targets and mechanistic pathways of vitamin A against diabetic foot ulcers
Figure 2. The Venn diagram (left) displaying the 66 intersection targets for vitamin A action against diabetic foot ulcers and protein-protein interaction network plot for the targets (right)
Figure 3. Identification of 18 core targets for VA action against diabetic foot ulcers: JUN, MAPK1, THRB, MAPK14, MTNR1B, CXCR3, ESR1, AR, HDAC1, IL-10, CNR1, DRD2, EGFR, ADRA2A, CCND1, RXRB, RARA, and RXRA
Figure 4. Bioinformatics analyses revealing the top biological processes associated with vitamin A action against diabetic foot ulcers
Figure 5. KEGG analysis of the signaling pathways for the pharmacological effects of vitamin A against diabetic foot ulcers
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