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image of Bingqing Gao Facilitates the Healing Process of Full-Thickness Skin Defects in Rat Wounds by Activating the PI3K/AKT Pathway

Abstract

Background

Trauma, resulting from mechanical factors, entails damage to human tissues or organs. Whether occurring during times of war or peace, trauma is prevalent, particularly skin defects arising from surgery or external injuries. The development and design of effective wound dressings have become paramount. Bingqing Gao(BQG), rooted in Chinese folk medicine, is employed explicitly in trauma treatment based on traditional Chinese medicine (TCM) theory. This study aims to elucidate how BQG facilitates full-thickness skin wound healing in Sprague Dawley (SD) rats.

Methods

Data collection commenced using two approaches: retrieval from TCM system pharmacology databases (TCMSP) and literature mining to compile the practical chemical components and targets of BQG. A drug-target network was constructed. Subsequently, disease targets related to wound healing were collected to select core targets and pathways, building a drug-disease target protein-protein interaction (PPI) network using the ClusterONE algorithm to identify core genes. Gene Ontology (GO) and KEGG enrichment analyses were conducted based on the Metascape database. Finally, molecular docking validation was performed on the screened core targets and core components. In terms of experimentation, an SD rat full-thickness skin defect model was established, and varying doses of BQG were applied. Healing area, HE staining, Masson staining, ELISA, PCR, and other methods were employed to validate cytokines, differential proteins, and pathways. The study collectively discusses the mechanism and targets by which BQG promotes full-thickness skin wound healing in SD rats.

Results

Through network pharmacology screening, we identified various active components, including resveratrol, Lithospermic acid B, sanguiinH-2, asernestioside A_qt, kaempferol, daidzein, quercetin, apigenin, and Medicarpin. The core targets encompass Interleukin-6 (IL-6), Protein Kinase B (AKT1), Vascular Endothelial Growth Factor A (VEGFA), Interleukin-1 beta (IL-1β), Tumor Protein 53 (TP53), Epidermal Growth Factor Receptor (EGFR), Tumor Necrosis Factor (TNF), Albumin (ALB), among others. Potential signaling pathways include Phosphoinositide 3-kinase (PI3K)/AKT, Tumor Necrosis Factor (TNF), Hypoxia-Inducible Factor-1 (HIF-1), and more. Molecular docking studies suggest a robust binding interaction between the active components of BQG and disease targets, indicating a potential regulation of cytokines through the PI3K/AKTsignaling pathway, thereby promoting wound healing. The results of the experiment revealed that, in comparison to the model group, both the rhb-FGF group and BQG-H group exhibit a noteworthy increase in the expression levels of PI3K and AKT genes. Concurrently, there is a significant decrease in the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Additionally, there is a substantial increase in the levels of Transforming Growth Factor-beta (TGF-β) and Vascular Endothelial Growth Factor (VEGF).

Conclusion

Network pharmacology results indicate that BQG promotes wound healing through multiple components, targets, and pathways. experimental results suggest that BQG may activate the PI3K/AKTsignaling pathway, inhibit the production and release of related pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, promote VEGF generation at the injury site, and enhance TGF-β signaling transduction, effectively regulates the inflammatory response at the site of injury, promotes vascular regeneration in the injury area, and induces the proliferation and migration of cells in the injury area, ultimately contributing to wound healing. This study establishes the foundation for a more profound understanding of the molecular mechanisms underlying BQG's promotion of wound healing and offers insights for future drug research on BQG.

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2025-02-04
2025-03-28

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Bingqing Gao Facilitates the Healing Process of Full-Thickness Skin Defects in Rat Wounds by Activating the PI3K/AKT Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0113862073311259240918081737
/content/journals/cchts/10.2174/0113862073311259240918081737
/content/journals/cchts/10.2174/0113862073311259240918081737
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  • Article Type:     Research Article
Keywords: Full-thickness skin defects ; TGF-β ; inflammatory factors ; VEGF ; wound healing ; PI3K/AKT ; molecular docking

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