Ginkgo biloba Flower Extract Accelerates the Wound Healing in Diabetic Rats by Inhibiting Inflammation and Ferroptosis.

Diabetic wounds are a common complication of diabetes mellitus (DM), with healing often impaired by ferroptosis and persistent inflammation. This study investigated the effects of Ginkgo biloba flower extract (GBF) on diabetic wound healing by focusing on inflammation and ferroptosis. Chemical composition analysis identified 123 compounds in GBF containing 73 active ingredients of flavonoids and 12 terpenoids. In vivo, GBF treatment significantly accelerated the wound healing process in diabetic rats, and GBF promoted epithelial regeneration and collagen deposition by increasing the expression of CD31 and VEGF. It also enhanced the formation of new blood vessels. Mechanistically, GBF could inhibit the inflammatory response by reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and inhibit the oxidative stress-induced ferroptosis by increasing the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4). Proteomics analysis further confirmed its regulatory effects on inflammation and iron metabolism pathways. In vitro, GBF promoted the survival and migration of rat skin fibroblasts (RS1) while reducing the levels of reactive oxygen species (ROS) and Fe2+ in erastin-induced ferroptosis cells. In conclusion, GBF promotes diabetic wound healing by inhibiting ferroptosis and inflammation.