Biliverdin improved angiogenesis and suppressed apoptosis via PI3K/Akt-mediated Nrf2 antioxidant system to promote ischemic flap survival

Plastic and reconstructive surgeons frequently utilize random skin flap transplantation to repair skin defects. However, the procedure carries a substantial risk of necrosis. Previous research has suggested that Biliverdin (Bv), the main component of Calculus Bovis, possessed potent anti-ischemic properties, making it a potential therapeutic agent for skin flap survival. Hence, in this study, the potential of Bv in promoting flap survival has been comprehensively investigated. Network pharmacology analysis revealed that the pharmacological effects of Bv on ischemic diseases may be attributed to its modulation of various signaling molecules, including the PI3K-Akt pathway. In vitro results demonstrated that Bv treatment significantly promoted angiogenesis in human umbilical vein endothelial cells (HUVEC), even in the presence of H