Retinal neovascularization is a major cause of vision loss in diseases characterized by
retinal ischemia and is characterized by the pathological growth of abnormal vessels.
Vascular endothelial growth factor (
VEGF) is known to play an important role in this process. Oxidative stress has been strongly implicated in up-regulation of
VEGF associated with neovascularization in various tissues. Hence, compounds with
anti-oxidant actions can prevent neovascularization. α-
Mangostin, a component of mangosteen (Garcinia mangostana Linn), has been shown to have an
anti-oxidant property in pathological conditions involving angiogenesis such as
cancer. However, the effect of α-
mangostin on ROS formation and angiogenic function in microvascular endothelial cells has not been studied. Hence, this study demonstrated the anti-angiogenic effects of α-
mangostin in relation to ROS formation in bovine
retinal endothelial cells (REC). α-
Mangostin significantly and dose-dependently reduced formation of ROS in
hypoxia-treated REC. α-
Mangostin also significantly and dose-dependently suppressed
VEGF-induced increases in permeability, proliferation, migration and tube formation in REC and blocked angiogenic sprouting in the ex vivo aortic ring assay. In addition, α-
mangostin inhibited
VEGF-induced phosphorylation of VEGFR2 and ERK1/2-MAPK. According to our results, α-
mangostin reduces oxidative stress and limits
VEGF-induced angiogenesis through a process involving abrogation of VEGFR2 and ERK1/2-MAPK activation.