Abstract
BACKGROUND: Diabetic wounds are one of the most common complications of diabetes mellitus. Jingfang Granules (JFG), a combination of 11 herbs, has been clinically used for treating colds and the flu and for preventing various skin diseases. PURPOSE: The present study was designed to evaluate the therapeutic effect of JFG on diabetic wounds and to elucidate the associated mechanisms. METHODS: JFG serum was prepared using Sprague-Dawley rats and the phytochemicals of JFG in the serum were identified using UHPLC-ESI-QE-Orbitrap-MS. A cell viability assay and cellular angiogenesis methods were performed to evaluate wound healing in vitro. Diabetic wounds were developed using streptozotocin-induced diabetic rats to investigate the efficacy of JFG on diabetic wounds in vivo. Network pharmacology analysis, molecular docking, and Western blot were performed to elucidate the potential mechanisms of JFG in diabetic wound healing. RESULTS: JFG serum attenuated H(2)O(2)-induced and high glucose-induced oxidative damage, significantly reduced lipopolysaccharide-induced upregulation of inflammatory cytokines, and promoted angiogenesis in vitro. In diabetic rats, JFG effectively promoted wound healing, reduced blood glucose and lipid levels, and alleviated oxidative stress and inflammation. A total of 56 phytochemicals were identified in the JFG serum. Six core targets (AKT1, EGFR, MAPK3, MAPK1, IL6, and TNF) and the PI3K-AKT and MAPK signaling pathways were identified by network pharmacology analysis, which were further validated by subsequent experimental methods. CONCLUSION: JFG could accelerate diabetic wound healing by alleviating oxidative damage, suppressing inflammation, promoting angiogenesis, and regulating metabolic abnormalities, with involvement of the PI3K-AKT and MAPK signaling pathways.