title: Anthocyanin-rich purple corn extract inhibit diabetes-associated glomerular angiogenesis.
abstract: Diabetic nephropathy (DN) is one of the major diabetic complications and the leading cause of end-stage renal disease. Abnormal angiogenesis results in new vessels that are often immature and play a pathological role in DN, contributing to renal fibrosis and disrupting glomerular failure. Purple corn has been utilized as a daily food and exerts disease-preventive activities. This study was designed to investigate whether anthocyanin-rich purple corn extract (PCE) prevented glomerular angiogenesis under hyperglycemic conditions. Human endothelial cells were cultured in conditioned media of mesangial cells exposed to 33 mM high glucose (HG-HRMC-CM). PCE decreased endothelial expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF)-1α induced by HG-HRMC-CM. Additionally, PCE attenuated the induction of the endothelial marker of platelet endothelial cell adhesion molecule (PECAM)-1 and integrin β3 enhanced in HG-HRMC-CM. Endothelial tube formation promoted by HG-HRMC-CM was disrupted in the presence of PCE. In the in vivo study employing db/db mice treated with 10 mg/kg PCE for 8 weeks, PCE alleviated glomerular angiogenesis of diabetic kidneys by attenuating the induction of VEGF and HIF-1α. Oral administration of PCE retarded the endothelial proliferation in db/db mouse kidneys, evidenced by its inhibition of the induction of vascular endothelium-cadherin, PECAM-1 and Ki-67. PCE diminished the mesangial and endothelial induction of angiopoietin (Angpt) proteins under hypeglycemic conditions. The induction and activation of VEGF receptor 2 (VEGFR2) were dampened by treating PCE to db/db mice. These results demonstrate that PCE antagonized glomerular angiogenesis due to chronic hyperglycemia and diabetes through disturbing the Angpt-Tie-2 ligand-receptor system linked to renal VEGFR2 signaling pathway. Therefore, PCE may be a potent therapeutic agent targeting abnormal angiogenesis in DN leading to kidney failure.
authors.affiliation: Department of Food and Nutrition and Center for Aging and Healthcare, Hallym University, Chuncheon, Korea.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kang
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Kyung Mok
authors.initials: KM
authors.lastname: Yeo
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D066298:In Vitro Techniques; D039661:Integrin beta3 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D003313:Zea mays / Q000737:chemistry*; D000099152:Cadherin 5
chemical_list: D000872:Anthocyanins; D015703:Antigens, CD; D015820:Cadherins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D039661:Integrin beta3; D010936:Plant Extracts; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5