Calycosin accelerates wound healing in diabetic rats by alleviating oxidative stress and promoting angiogenesis.

Angiogenesis is a physiological process of diabetic wound healing. Although calycosin has been reported to exert protective effects on diabetic nephropathy, its role and mechanisms in diabetic wound healing remain unclear. This study investigates the effects of calycosin on wound healing and angiogenesis, and the role of the Nrf2/HO-1 pathway in mitigating oxidative stress in diabetic rats. In vivo, type 2 diabetes (T2DM) in Sprague-Dawley (SD) rats was induced by a high-fat diet for six weeks combined with a single intraperitoneal injection of 45 mg/kg streptozotocin (STZ). The anesthetized diabetic rats underwent a full skin excision on the back and were then treated with calycosin for two weeks to evaluate the protective effect of calycosin on oxidative stress associated with the Nrf2/HO-1 pathway in diabetic wound rats. In vitro, damage to Human Umbilical Vein Vascular Endothelial Cells (HUVECs) was induced by high glucose, and then treated with calycosin or combined with Nrf2 agonist to evaluate whether calycosin affects cell activity and inhibits oxidative damage via the Nrf2/HO-1 pathway. Our results indicate that calycosin promotes angiogenesis by activating the Nrf2/HO-1 signaling pathway and upregulating downstream antioxidant genes, thereby accelerating wound healing. In vitro studies have also shown that Nrf2/HO-1 signaling activation can enhance the promoting effect of calycosin on cell activity and the inhibitory effect on oxidative stress in HUVECs induced by high glucose. Our results show that calycosin can accelerate wound healing by promoting angiogenesis and inhibiting oxidative stress mediated by the Nrf2/HO-1 pathway, which provides a theoretical basis for the treatment of refractory diabetic wounds.