title: Decursin inhibited proliferation and angiogenesis of endothelial cells to suppress diabetic retinopathy via VEGFR2.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Yunnan Province 2nd Hospital, Kunming 650031, China; Department of Internal Medicine, Division of Endocrinology, HSC Diabetes Center, University of Missouri, Columbia, MO 65201, USA; Laboratory for Conservation and Utilization of Bio-resources Yunnan University, Kunming 650021, China. Electronic address: yangying2072@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.forename: Xianli
authors.initials: X
authors.lastname: Li
authors.forename: Qiangming
authors.initials: Q
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Meng
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
chemical_list: D020533:Angiogenesis Inhibitors; D001578:Benzopyrans; D002087:Butyrates; C101278:decursin; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Decursin; Diabetic retinopathy; Proliferation; VEGFR-2