Curcumin promotes the survival of ischemic random skin flaps via autophagy

Random skin flaps have been widely applied in reconstructive and plastic surgery; however, necrosis usually happens due to insufficient blood supply in the ischemic area of flaps. Curcumin (CUR) is a primary bioactive compound of turmeric (Curcuma longa, L.), which has been proven to be effective on anticancer, decreasing oxidative stress and apoptosis through activating autophagy, and promoting angiogenesis in ischemic tissue. Therefore, the potential therapeutic effect of CUR on promoting survival of ischemic random skin flaps and its underlying mechanism associated with autophagy were investigated. After establishment of dorsal random skin flaps, sixty mice were randomly divided into three groups: Control, CUR or CUR+3-methyladenine (3-MA, an autophagy inhibitor). The results showed that CUR increased the viability area and blood flow as well as relieved the edema of skin flaps through promoting angiogenesis, decreasing oxidative stress, and inhibiting apoptosis of the ischemic area. Further study confirmed that CUR activated autophagy in the random skin flaps, and 3-MA effectively reversed the effect on viability, neovascularization, oxidative stress and apoptosis, suggesting autophagy played a vital role in these CUR's protective effect on random skin flaps. Moreover, this CUR-induced autophagy should be mediated through downregulating the PI3K/AKT/mTOR signaling pathway. Together with secondary response of increased angiogenesis, reduced oxidative stress and apoptosis, CUR effectively improved survival of random skin flaps in vivo. To sum up, our research showed the great potential of CUR using as a promising flap protective therapy for random skin flap survival and regeneration.