Bingqing Gao Facilitates the Healing Process of Full-Thickness Skin Defects in Rat Wounds by Activating the PI3K/AKT Pathway
Authors: Ma Hong’e , Hu Rui , Guo Jiajun , Wang Xinfu , Liu Xin , Zhang Ning , Ren Ruilong , Wang Danyang , Zhang Wenxian 
Published: February 2025

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 drugtarget
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 in vivo 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 in vivo 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. In vivo 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.