Purple corn anthocyanins retard diabetes-associated glomerulosclerosis in mesangial cells and db/db mice

Eur J Nutr. 2012 Dec;51(8):961-73. doi: 10.1007/s00394-011-0274-4. Epub 2011 Nov 20.

Abstract

Purpose: Diabetic glomerulosclerosis is the hardening of the renal glomeruli that can lead to kidney failure. In the early stage of glomerulosclerosis occur renal mesangial expansion and renal filtration dysfunction. Purple corn has been classified as a functional food and is rich in anthocyanins exerting potential disease-preventive activities. The in vitro study using human renal mesangial cells examined that anthocyanin-rich purple corn butanol fraction (PCB) can attenuate high glucose (HG)-promoted mesangial cell proliferation and matrix accumulation.

Methods: Cells were cultured for 3 days in media containing 33 mM glucose in the presence of 1-20 μg/mL PCB. In the in vivo animal study, db/db mice were treated with 10 mg/kg anthocyanin-rich polyphenolic extracts of purple corn (PCE) for 8 weeks.

Results: HG enhanced mesangial production of the fibrosis biomarkers of collagen IV and connective tissue growth factor (CTGF), which was markedly attenuated by adding PCB. Such mesangial fibrosis entailed interleukin-8 activation via eliciting Tyk2-STAT signaling pathway. PCB dampened HG-promoted mesangial hyperplasia that appeared to be attributed to increased expression of platelet-derived growth factor. The 8-week administration of PCE lowered plasma glucose level of db/db mice and ameliorated severe albuminuria. Moreover, PCE lessened collagen fiber accumulation in kidney glomeruli and CTGF expression via retarding TGF-β signaling. Protein expressions of nephrin and podocin, key proteins for filtration barrier function of the glomerular capillary wall, were repressed by treating mice with PCE.

Conclusion: Purple corn may be a potent therapeutic agent for the treatment for diabetes-associated glomerulosclerosis accompanying proteinuria and kidney filtration dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / drug therapy
  • Albuminuria / pathology
  • Animals
  • Anthocyanins / pharmacology*
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Cell Proliferation / drug effects
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / pathology
  • Fibrosis / drug therapy
  • Fibrosis / pathology
  • Humans
  • Interleukin-8 / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mesangial Cells / drug effects*
  • Mesangial Cells / metabolism
  • Mice
  • Plant Extracts / pharmacology*
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Proteinuria / complications
  • Proteinuria / drug therapy
  • Proteinuria / pathology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • TYK2 Kinase / genetics
  • TYK2 Kinase / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Zea mays / chemistry*

Substances

  • Anthocyanins
  • Biomarkers
  • Blood Glucose
  • CCN2 protein, mouse
  • Collagen Type IV
  • Interleukin-8
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Plant Extracts
  • Platelet-Derived Growth Factor
  • STAT Transcription Factors
  • Transforming Growth Factor beta
  • nephrin
  • Connective Tissue Growth Factor
  • TYK2 Kinase
  • Tyk2 protein, mouse