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

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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.

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Abbreviations

CTGF:

Connective tissue growth factor

DN:

Diabetic nephropathy

ECM:

Extracellular matrix

HG:

High glucose

HRMC:

Human renal mesangial cells

IL:

Interleukin

MMP:

Matrix metalloproteinases

MT1-MMP:

Membrane type-1 matrix metalloproteinase

PCB:

Anthocyanin-rich purple corn butanol extract

PCE:

Anthocyanin-rich polyphenolic extracts of purple corn

PDGF:

Platelet-derived growth factor

TGF:

Transforming growth factor

TIMP:

Tissue inhibitor of metalloproteinases

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Acknowledgments

This study was supported by the grant from the Ministry for Food, Agriculture, Forestry and Fisheries through Korea Institute of Planning and Evaluation for Technology of Food, Agriculture, Forestry and Fisheries (109163-03-1-SB030) and by the Korea Research Foundation grant funded by the Korean Government (MEST), the Regional Research Universities Program/Medical & Bio-Materials Research Center.

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Authors and Affiliations

  1. Department of Food and Nutrition, Hallym University, Chuncheon, Kangwon-do, 200-702, South Korea

    Jing Li, Min-Kyung Kang, Jung-Lye Kim, Sang-Wook Kang, Soon Sung Lim & Young-Hee Kang

  2. Institute of Natural Medicine, Hallym University, Chuncheon, 200-702, Korea

    Jin-Kyu Kim

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  1. Jing Li
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  2. Min-Kyung Kang
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Correspondence to Young-Hee Kang.

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Jing Li and Min-Kyung Kang contributed equally to this work.

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Li, J., Kang, MK., Kim, JK. et al. Purple corn anthocyanins retard diabetes-associated glomerulosclerosis in mesangial cells and db/db mice. Eur J Nutr 51, 961–973 (2012). https://doi.org/10.1007/s00394-011-0274-4

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  • DOI: https://doi.org/10.1007/s00394-011-0274-4

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