Pinocembrin alleviates pyroptosis and apoptosis through ROS elimination in random skin flaps via activation of SIRT3

Abstract

Random skin flap grafting is the most common skin grafting technique in reconstructive surgery. Despite progress in techniques, the incidence of distal flap necrosis still exceeds 3%, which limits its use in clinical practice. Current methods for treating distal flap necrosis are still lacking. Pinocembrin (Pino) can inhibit reactive oxygen species (ROS) and cell death in a variety of diseases, such as cardiovascular diseases, but the role of Pino in random flaps has not been explored. Therefore, we explore how Pino can enhance flap survival and its specific upstream mechanisms via macroscopic examination, Doppler, immunohistochemistry, and western blot. The results suggested that Pino can enhance the viability of random flaps by inhibiting ROS, pyroptosis and apoptosis. The above effects were reversed by co‐administration of Pino with adeno‐associated virus‐silencing information regulator 2 homolog 3 (SIRT3) shRNA, proving the beneficial effect of Pino on the flaps relied on SIRT3. In addition, we also found that Pino up‐regulates SIRT3 expression by activating the AMP‐activated protein kinase (AMPK) pathway. This study proved that Pino can improve random flap viability by eliminating ROS, and ROS‐induced cell death through the activation of SIRT3, which are triggered by the AMPK/PGC‐1α signaling pathway.

Metabolomics combined with network pharmacology reveals a role for astragaloside IV in inhibiting enterovirus 71 replication via PI3K-AKT signaling

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Liguzinediol ameliorates doxorubicin-induced cardiotoxicity and potentiates the metabolic remodeling by activating the AMPK/SIRT3 pathway and represses Caspase-3/GSDME-mediated pyroptosis

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Dihydromyricetin regulates KEAP1‐Nrf2 pathways to enhance the survival of ischemic flap

“…This decreases the anoxic and hypoxic environment as well as the necrosis of the distal flap. Lack of blood flow to the distal flap might result in ischemia and anoxia, which can lead to the accumulation of reactive oxygen species (ROS) (Li, Li, et al., 2023 ). In addition to causing cell damage and death, the buildup of ROS also causes the generation of additional oxygen‐free radicals, creating a vicious cycle of oxidative stress and cell death (Liu, Sun, et al., 2022 ; Stockwell et al., 2017 ).…”