Baicalin-loaded chitosan hydrogel accelerates diabetic foot ulcer healing by regulating MAPK1 expression

Diabetic foot ulcer (DFU) is a severe complication of diabetes. This study evaluated the effects and underlying mechanism of baicalin on DFU healing. High glucose (HG)-exposed HaCaT cells and streptozotocin-induced DFU rats were employed as in vitro cell models and in vivo models. Cell viability, migration, and inflammatory cytokine levels were assessed following baicalin (100 µg/mL) treatment. A baicalin-loaded carboxymethyl chitosan (CS) hydrogel was prepared, and its therapeutic effects on blood glucose and wound closure were evaluated over 14 days. Bioinformatic analysis, molecular docking, and MAPK1 knockdown were performed to elucidate the mechanism. Baicalin restored HG-reduced HaCaT cell viability (p < 0.01) and migration (p < 0.001), and decreased IL-6, IL-1β, and TNF-α levels. In DFU rats, the hydrogel lowered blood glucose from > 20 mM to approximately 10 mM (p < 0.001) and accelerated wound healing (p < 0.01). Bioinformatic analysis identified MAPK1 as a key target; molecular docking confirmed strong binding affinity (< - 6 kcal/mol). Baicalin upregulated MAPK1 expression (p < 0.01), whereas shRNA-mediated MAPK1 knockdown attenuated the therapeutic effects in vitro and in vivo (p < 0.001). These findings demonstrate baicalin's potential as a DFU treatment through MAPK1 regulation and highlight the need for further research into its molecular mechanisms and clinical applications.