Abstract

Hyperglycemia-induced oxidative stress considerably hinders healing of diabetic wounds, primarily due to mitochondrial dysfunction. This pathology leads to an excessive production of reactive oxygen species (ROS), disrupts respiratory chain function, and impairs energy metabolism. This study introduces procyanidin (PC) capsules designed to target the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. The PC capsules demonstrate a sustained ability to scavenge radicals, thereby directly lowering ROS levels and specifically activating the PI3K/AKT pathway. Through this activation, the capsules restore mitochondrial function by reducing mitochondrial reactive oxygen species, stabilizing mitochondrial membrane potential, and restoring energy production. Additionally, cell experiments reveal that the capsules significantly boost the migration of fibroblasts and enhance the angiogenic activity of endothelial cells, indicating the protective effects of PC on crucial cell functions involved in wound healing. In a chronic skin wound model of diabetic mice, the PC capsules are found to accelerate wound closure by promoting collagen deposition, suppressing excessive inflammation, and minimizing mitochondrial oxidative damage. Using the PI3K inhibitor LY294002, we further verified that the pro-migratory and pro-angiogenic effects of PC capsules are largely dependent on PI3K/AKT signaling. Our novel findings suggest that PC capsules stimulate PI3K/AKT-mediated repair of mitochondrial function, presenting a potential therapeutic approach for treating refractory diabetic wounds.