decursin and Diabetic-Retinopathy

Diabetes induces pathologic proliferation and angiogenesis in the retina that leads to catastrophic loss of vision. Decursin is a novel therapeutic that targets the vascular endothelial growth factor (VEGF) receptor (VEGFR) with putative anti-proliferative and anti-angiogenic activities. Thereby we utilized human retinal microvascular endothelial cells (HRMEC) and human umbilical vein endothelial cells (HUVEC) under conditions of excess glucose to explore dose-dependent responses of decursin on markers of migration, angiogenesis, and proliferation. Decursin dose-dependently inhibited tube formation, VEGFR-2 expression, along with relative metabolic activity and 5-bromo-2'-deoxy-uridine (BrdU) activity in both cell lines. We then correlated our findings to the streptozotocin-induced rat model of diabetes. Following three months of decursin treatment VEGFR-2 expression was significantly inhibited. Our data would suggest that decursin may be a potent anti-angiogenic and anti-proliferative agent targeting the VEGFR-2 signaling pathway, which significantly inhibits diabetic retinal neovascularization.

Topics: Angiogenesis Inhibitors; Animals; Benzopyrans; Butyrates; Cell Proliferation; Diabetic Retinopathy; Dose-Response Relationship, Drug; Endothelial Cells; Gene Expression Regulation, Enzymologic; Human Umbilical Vein Endothelial Cells; Humans; Neovascularization, Pathologic; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor Receptor-2