ß-Caryophyllene promotes the survival of random skin flaps by upregulating the PI3K/AKT signaling pathway.

ABSTRACT

BACKGROUND: Flap transplantation is a widely used plastic repair technique in surgical procedures, aimed at addressing skin defects resulting from diverse wounds and diseases. However, due to the insufficient blood supply after flap surgery, the occurrence of ischemia-reperfusion injury, and an excessive sterile inflammatory response, flaps frequently develop complications (e.g., partial or complete ischemic necrosis). These complications have adverse effects on wound healing and repair. ß-Caryophyllene (BCP) is a bicyclic sesquiterpene that is widely present in plants. It mitigates oxidative stress and inflammatory responses, demonstrates neuroprotective and analgesic properties, and serves a protective function in organs or tissues subjected to ischemia-reperfusion injury. However, no study has confirmed whether BCP can be used in the field of flap transplantation to improve the flap survival rate. METHODS: To assess the impact of BCP on random flap survival, we constructed a modified McFarlane random flap model on the rat. After 7 consecutive days of gavage with different doses of BCP, we measured the survival area ratio, angiogenesis, blood perfusion, tissue inflammation level, apoptosis-related protein levels, and the PI3K/AKT signaling pathway expression of the random flap. RESULTS: BCP treatment increased the survival area of the flap in a dose-dependent manner after random flap transplantation in rats. BCP mainly promoted the formation of tissue blood vessels, improved flap blood perfusion, limited the local inflammatory response, and reduced apoptosis. In addition, we demonstrated that BCP works primarily by promoting the PI3K/AKT signaling expression while enhancing the phosphorylation of AKT. Administration of wortmannin, a selective inhibitor of PI3K, eliminated the effects of BCP. CONCLUSION: BCP can promote the survival of random flaps by upregulating the PI3K/AKT signaling pathway, increasing tissue blood perfusion, and limiting the inflammatory response and apoptosis.