Salvianolic acid B enhances adipose-derived stem cells (ADSCs)-mediated perforator flap survival through antioxidative and anti-apoptotic mechanisms.

Skin flap transplantation is often complicated by ischemia-reperfusion injury, leading to tissue necrosis. Salvianolic acid B (Sa B), a key component of Salvia miltiorrhiza, possesses known antioxidative and anti-apoptotic properties. This study investigated whether Sa B preconditioning could enhance the regenerative capacity of adipose-derived stem cells (ADSCs) before transplantation for improving flap survival. We assessed the effects of Sa B on ADSCs viability, migration, differentiation, and resilience to oxidative stress in vitro under normal and oxygen-glucose deprivation (OGD) conditions. Sa B significantly enhanced ADSC viability, proliferation, and migration, while reducing intracellular ROS accumulation and activating antioxidant responses. A mouse perforator flap model was subsequently established to evaluated the in vivo therapeutic efficacy of Sa B-preconditioned ADSCs. Sa B significantly improved ADSCs viability, proliferation, and migration, while reducing intracellular ROS and activating antioxidant responses. Sa B also promoted ADSCs differentiation towards an endothelial lineage and enhanced angiogenic potential. Mechanistically, Sa B enhanced Nrf2/HO-1-mediated antioxidative defense and promoted PI3K/AKT signaling, resulting in increased anti-apoptotic protein expression and reduced mitochondrial apoptosis. In vivo, transplantation of Sa B-preconditioned ADSCs markedly improved flap survival, tissue regeneration, angiogenesis, and cellular proliferation, accompanied by enhanced antioxidant and anti-apoptotic responses. In conclusion, our findings identify Sa B as a promising pharmacological preconditioning agent that improves the intrinsic regenerative capacity of ADSCs through coordinated antioxidative and anti-apoptotic mechanisms. This strategy provides a potential approach for optimizing ADSCs-based therapy and improving flap survival in reconstructive surgery.