Exploring the potential mechanisms of Tangzukang Ointment against diabetic foot ulcers based on network pharmacology prediction and molecular docking approach.

Tangzukang Ointment (T-Ointment) is formulated by adding ingredients such as Astragalus, Angelica sinensis, Cinnamomi Cortex, and Coix seed to the traditional formula ErMiao Pill. This ointment has the effects of clearing heat and removing dampness, warming the yang energy, strengthening the qi, promoting blood circulation and tissue regeneration. Clinically, it is used by traditional Chinese medicine to treat diabetic foot ulcers (DFU). This study established an experimental rat model of ischemic DFU to investigate its therapeutic effect and potential mechanism in DFU. The results showed that T-Ointment significantly promoted wound healing in diabetic rats by inhibiting excessive inflammation, promoting epithelial regeneration, angiogenesis and collagen deposition. Network pharmacology analysis indicated that the core compounds (quercetin, phellochin, fumarine, poriferast-5-en-3beta-ol, and jaranol) in T-Ointment targeted multiple key genes (AKT1, TGF-β, HIF-1, TNF, IL-6, EGFR, TP53 and MAPK) and were closely associated with multiple important signaling pathways (PI3K/AKT, EGFR, TGF-β/Smad, and MAPK/ERK etc.). Analysis of combined results from KEGG pathway enrichment analysis and molecular docking, the key pathways potentially promoted by T-Ointment for diabetic foot ulcer healing were identified: the PI3K/AKT and EGFR pathways. Further research has confirmed that T-Ointment indeed reversed the downregulation of the PI3K/AKT and EGFR pathways in the diabetic foot ulcer group. This indicates that its role in accelerating ulcer healing is closely related to the activation of these two pathways. In conclusion, this study clarified the multi-component, multi-target and multi-pathway mechanism of T-Ointment in treating diabetic foot ulcers, providing a scientific basis for its clinical application.