Berberine promotes the viability of random skin flaps via the PI3K/Akt/eNOS signaling pathway

Abstract Random skin flaps are often used in reconstruction operations. However, flap necrosis is still a common postoperative complication. Here, we investigated whether berberine (C 20 H 19 NO 5 , BBR), a drug with antioxidant activity, improves the survival rate of random flaps. Fifty‐four rats were divided into three groups: control, BBR and BBR + L ‐NAME groups ( L ‐NAME, L ‐N G ‐Nitro‐arginine methyl ester). The survival condition and the percentage of survival area of the flaps were evaluated on the seventh day after surgery. After animals were sacrificed, angiogenesis, apoptosis, oxidative stress and inflammation levels were assessed by histological and protein analyses. Our findings suggest that berberine promotes flap survival. The level of angiogenesis increased; the levels of oxidative stress, inflammation and apoptosis decreased; the levels of phosphoinositide 3‐kinase (PI3K), phospho‐Akt (p‐Akt) and phospho‐endothelial nitric oxide synthase (p‐eNOS) increased in the flap tissue; and L ‐NAME reversed the effects of berberine on random skin flaps. Statistical analysis showed that the BBR group results differed significantly from those of the control and the BBR + L ‐NAME groups ( p < .05). Our results confirm that berberine is an effective drug for significantly improving the survival rate of random skin flaps by promoting angiogenesis, inhibiting inflammation, attenuating oxidative stress, and reducing apoptosis through the PI3K/Akt/eNOS signaling pathway.