Mechanisms of Huhuang decoction in treating diabetic wounds: a network pharmacological and experimental study.

Abstract

Background: Huhuang (HH) decoction, a composition of seven traditional Chinese medicines, has demonstrated clinical efficacy in wound healing. However, its pharmacological foundation and potential mechanisms remain unclear. This study aimed to elucidate the mechanisms of action of HH decoction in the treatment of diabetic wounds. Methods: The chemical composition of HH decoction was analysed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The targets of the HH decoction in treating diabetic wounds were predicted using network pharmacology. The gene ontology and pathway enrichment analyses were performed using the DAVID functional annotation tool. The compound targets and PPI networks were established using Cytoscape. Molecular docking was implemented using the AutoDock Vina software. Experimental verification was performed on the target prediction of the HH decoction in treating diabetic wounds, both in vivo and in vitro. Results: The study identified 53 chemical components in HH decoction, with tetrahydropalmatine, emodin, rosmarinic acid, citric acid, berberine, and cryptotanshinone as key components for treating diabetic wounds. Twenty-one target genes were identified as core genes. Gene ontology analysis indicated that the therapeutic effects of HH on diabetic foot ulcers may occur through the regulation of cell proliferation, migration, and inflammation. Pathway enrichment was found to be mainly related to the HIF-1 and TNF signalling pathways. HH promoted proliferation, migration, and tube formation in vascular endothelial cells in vitro. Compared with the control group, the expression levels of HIF-1α, VEGF-α, cyclinD1 in the HH group were higher while the phosphorylation level of p65 in the HH group was significantly lower. The concentrations of IL-6, TNF-α, and IL-1β in wound tissue in the HH group were significantly lower than those in the control group. The expression levels of CD31, VEGF-α, Ki67 and HIF-1α in the wounds of diabetic rats in the HH group were higher than those in the control group. Conclusions: The HH decoction promotes diabetic wound healing via multiple components, targets, and pathways. It may enhance vascular endothelial cell proliferation via cyclinD1, promote vascularization through the HIF-1α/VEGF-α signalling pathway, and inhibit inflammation through NF-κB signalling pathways.