Integrating Transcriptomics, Network Pharmacology, Molecular Docking and Experimental Validation to Explore the Pharmacological Mechanisms of Chinese Medicinal Honey in Treating Diabetic Wounds

ABSTRACT

Chinese medicinal honey (CMH) is traditionally used for wounds, but its mechanisms in diabetic wounds are unclear. This study aimed to investigate the active components of CMH and the molecular mechanisms underlying its promotion of wound healing in individuals with diabetes to provide a preliminary experimental basis for its clinical application. The main components of CMH were analysed using ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS). An integrated strategy combining network pharmacology, transcriptomics, molecular docking and animal experiments was applied. A db/db diabetic mouse model was used to evaluate CMH in diabetic wound healing. Histopathology, immunohistochemistry, qRT‐PCR and western blotting were performed to assess anti‐inflammatory, antioxidant and pro‐angiogenic effects. Fifty‐two major CMH components, mainly flavonoids and phenolic acids, were identified. Network pharmacology and transcriptomics showed that CMH targets epidermal growth factor receptor (EGFR), interleukin (IL)‐1β, matrix metallopeptidase 9 (MMP9) and prostaglandin‐endoperoxide synthase 2 (PTGS2), with significant enrichment in the IL‐17 signalling pathway. Molecular docking validated a strong binding affinity between CMH components and key targets, including IL‐17A and NF‐κB. In vivo findings suggest that CMH markedly accelerates wound healing in diabetic mice, reduces inflammation and oxidative stress, promotes collagen deposition and angiogenesis and suppresses the activity of the IL‐17A/NF‐κB pathway. This study provides a preliminary experimental basis of CMH. CMH supports diabetic wound healing through a multi‐component, multi‐target mechanism, primarily by inhibiting the IL‐17A/NF‐κB signalling pathway, thereby attenuating inflammation and oxidative stress and promoting angiogenesis and tissue repair.