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: Min-Kyung Kang, Soon Sung Lim, Jae-Yong Lee, Kyung Mok Yeo, Young-Hee Kang
• Journal: PloS one (PLoS One) Vol. 8 Issue 11 Pg. e79823 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24278186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthocyanins
• Antigens, CD
• Cadherins
• Hypoxia-Inducible Factor 1, alpha Subunit
• Integrin beta3
• Plant Extracts
• Platelet Endothelial Cell Adhesion Molecule-1
• Thrombospondin 1
• Vascular Endothelial Growth Factor A
• cadherin 5

Topics

• Animals
• Anthocyanins (metabolism)
• Antigens, CD (metabolism)
• Blotting, Western
• Cadherins (metabolism)
• Cell Line
• Cell Proliferation (drug effects)
• Diabetes Mellitus (drug therapy)
• Enzyme-Linked Immunosorbent Assay
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• In Vitro Techniques
• Integrin beta3 (metabolism)
• Kidney Glomerulus (blood supply, cytology)
• Male
• Mice
• Mice, Inbred C57BL
• Neovascularization, Pathologic (drug therapy)
• Plant Extracts (pharmacology, therapeutic use)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Thrombospondin 1 (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)
• Zea mays (chemistry)