Nobiletin enhances the survival of random pattern skin flaps: Involvement of enhancing angiogenesis and inhibiting oxidative stress

Random-pattern flap necrosis is a serious challenge for plastic surgeons. Nobiletin (NOB) is a polymethoxylated flavonoid extracted from citrus fruits reported to have antioxidant, anti-inflammatory and anti-apoptotic effects. Our experiment evaluated the impact of NOB on the viability of random flaps. Thirty six male "McFarlane flap" rat models were separated into two equal groups: a control group and an experimental group treated with 10 mg/kg of NOB. After 7 days, the range of necrosis was calculated, and a histological analysis was performed on tissue specimens. Immunohistochemical staining, lead oxide-gelatin angiography, and a Laser Doppler perfusion imager were used to assess angiogenesis and measure oxidative stress, as indicated by superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. The average survival area of flap was greater in the NOB-treated group than that in the control group. The NOB-treated group mitigated oxidative stress via augmented SOD, reduced MDA, and enhanced vascular endothelial growth factor (VEGF) expression. Hematoxylin and eosin staining indicated that NOB increased blood flow and had anti-inflammatory effects. Our findings revealed that NOB improved random skin flap survival.