Anthocyanin-rich Seoritae extract ameliorates renal lipotoxicity via activation of AMP-activated protein kinase in diabetic mice

J Transl Med. 2015 Jun 27:13:203. doi: 10.1186/s12967-015-0563-4.

Abstract

Background: Anthocyanins are major constituents of food colours and have been reported to possess anti-diabetic activities for potential medicinal use. The precise role of anthocyanins in diabetic nephropathy is poorly understood. We investigated whether anthocyanin-rich Seoritae extract (SE) can potentially prevent oxidative stress and lipotoxicity, which are the main causes of renal damage in diabetic nephropathy, via activation of AMP-activated protein kinase (AMPK) and the consequent effects on its target molecules.

Methods: Four groups of male C57BLKS/J db/m and db/db mice were used. Diabetic and non-diabetic mice were orally administered 10 mg/kg body weight SE daily for 12 weeks, starting at 8 weeks of age.

Results: db/db mice treated with anthocyanins showed decreased albuminuria. Anthocyanins ameliorated intra-renal lipid concentrations in db/db mice with improvement of glomerular matrix expansion and inflammation, which was related to increased phosphorylation of AMPK and activation of peroxisome proliferator-activated receptor (PPAR) α and PPARγ, and inhibited the activity of acetyl-CoA carboxylase and sterol regulatory element-binding protein 1. Anthocyanins reversed diabetes-induced increases in renal apoptosis and oxidative stress. In cultured human glomerular endothelial cells, anthocyanins prevented high glucose-induced oxidative stress and apoptosis through activation of AMPK in the same manner.

Conclusions: The results revealed that anthocyanins ameliorated diabetic nephropathy in db/db mice via phosphorylation of AMPK, the major energy-sensing enzyme, and the consequent effects on its target molecules, which appeared to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Anthocyanins / pharmacology
  • Anthocyanins / therapeutic use*
  • Apoptosis / drug effects
  • Cholesterol / metabolism
  • Collagen Type IV / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / pathology
  • Dinoprost / analogs & derivatives
  • Dinoprost / urine
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism
  • Glycine max / chemistry
  • Humans
  • Kidney / drug effects
  • Kidney / enzymology
  • Kidney / pathology*
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / enzymology
  • Kidney Diseases / pathology
  • Lipids / toxicity*
  • Male
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Phenotype
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Transforming Growth Factor beta / metabolism
  • Triglycerides / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anthocyanins
  • Collagen Type IV
  • Fatty Acids
  • Lipids
  • Plant Extracts
  • Transforming Growth Factor beta
  • Triglycerides
  • bcl-2-Associated X Protein
  • 8-epi-prostaglandin F2alpha
  • Cholesterol
  • Dinoprost
  • AMP-Activated Protein Kinases