Tyrosol promotes skin flap survival by downregulating the p38/NF-κB signaling pathway.

Skin flaps are often used to repair wounds and improve a patient's appearance, particularly after severe burns. Although skin flaps are widely used, they are prone to necrosis, which poses a major clinical challenge. Tyrosol is a natural phenolic antioxidant found in olive oil that has anti-inflammatory, anti-apoptotic, antioxidant, and pro-angiogenic properties. Despite the recognition of these properties, no studies have investigated the effects of tyrosol on flap survival, although tyrosol significantly reduced flap edema and the necrotic area. In a rat study using the McFarland random flap model, gelatin lead oxide angiography showed that angiogenesis was increased significantly in high- and low-dose tyrosol groups. These immunohistochemistry findings highlight the impact of tyrosol on the inflammatory response and angiogenesis, underscoring its potential significance in flap survival. Western blot analysis showed that the expression of p38, NF-κB, and BAX was significantly down-regulated, while that of Bcl-2 was significantly up-regulated, in the high- and low-dose tyrosol groups. This modulation of key signaling pathways and apoptotic proteins not only validates the impact of tyrosol but also reinforces its role in providing protection, thus promoting flap survival. In summary, tyrosol may inhibit inflammation, oxidative stress, and apoptosis by downregulating the p38-NF-κB signaling pathway and promoting angiogenesis, thereby enhancing skin flap survival.