Diosgenin promotes skin flap survival by attenuating oxidative stress and apoptosis via LKB1/AMPK-mediated autophagy.

Skin flap transplantation is a critical procedure for treating soft tissue defects and correcting external deformities. However, its widespread application is limited by the high incidence of post-operative flap necrosis. Research has demonstrated that multiple factors contribute to flap necrosis, including ischemia-reperfusion(I/R) injury, inflammatory responses, and apoptosis. As a daily food source, Dioscorea opposita contains Diosgenin-a compound with antioxidant properties that exemplifies the "medicine food homology" concept. This study investigated the effects of this Dioscorea opposita-derived Diosgenin on skin flap survival and its underlying mechanisms. McFarlane skin flap models were established in 48 male Sprague-Dawley rats, including: a control group, positive control group (nitrol ointment treatment group) and five dose-escalation groups with concentrations of 10, 25, 50, 100, and 200 mg/kg, respectively. Blood perfusion was measured using laser Doppler imaging. Inflammatory cytokines were evaluated using immunofluorescence staining. Western blot analysis was employed to assess the expression levels of proteins associated with autophagy, oxidative stress, and apoptosis. Additionally, CCK-8 was used to explore the toxicity of diosgenin, and ROS levels were determined in vitro. The research shows that diosgenin treatment enhanced the survival rate of skin flaps, attenuated neutrophil infiltration. Furthermore, diosgenin markedly reduced the expression of related protein of oxidative stress and apoptosis, while upregulating autophagy through the LKB1/AMPK pathway. The AMPK inhibitor Compound C was able to reverse the effects of diosgenin. The conclusion is that diosgenin promotes flap survival by reducing oxidative stress and apoptosis through LKB1/AMPK mediated autophagy.