Salidroside suppresses hyperglycemia-induced M1 macrophage polarization to accelerate diabetic wound healing by...

Aberrant wound healing capability is one of the main complications in diabetic patients. High blood glucose level and continuous inflammatory factors release leads to an excessive number of M1 macrophages, thereby causing various pathological conditions and ultimately weakening wound healing capacity. Hence, recovering macrophages homeostasis is a potential strategy for promoting diabetic wound healing potential. Meanwhile, salidroside is a small-molecule glycosidic compound which has been known for its antitumor, antioxidation, antiviral, and antiaging functions. However, whether salidroside could suppress M1 macrophage polarization and thereby restore wound healing potential under hyperglycemic conditions remains unclear. Herein, through transcriptomic analysis followed by in vitro and in vivo experiments, we revealed that salidroside could significantly suppress hyperglycemia-induced M1 macrophage polarization, and ultimately, promote diabetic wound healing. Mechanistically, salidroside could block hyperglycemia-induced mTOR signaling pathway activation in macrophages, thereby restraining glycolysis and suppressing M1 macrophage polarization. Together, these findings revealed that salidroside can suppress M1 macrophage polarization in diabetic mice by negatively regulating the mTOR signaling pathway, and thus promotes diabetic wound healing. These findings provide new insights into the anti-inflammatory function of salidroside and its potential as a small molecular compound for enhancing diabetic wound healing.