Specific bioactive compounds in ginger and apple alleviate hyperglycemia in mice with high fat diet-induced obesity via Nrf2 mediated pathway

Food Chem. 2017 Jul 1:226:79-88. doi: 10.1016/j.foodchem.2017.01.056. Epub 2017 Jan 16.


Prolonged hyperglycemia activates the formation of advanced glycation end-products (AGEs). Major dicarbonyl compounds such as methylglyoxal or glyoxal are found to be the main precursors of AGEs and N(ε)-(carboxymethyl)lysine (CML) found to be predominantly higher in the diabetic population. We hypothesized that phloretin from apple and [6]-gingerol from ginger inhibit formation of AGEs and suppress the receptor for advanced glycation end products (RAGE) via nuclear factor erythroid-2-related-factor-2 (Nrf2)-dependent pathway. Phloretin and [6]-gingerol were supplemented at two different doses to C57BL/6 mice on high fat diet or standard diet for a period of 17weeks. Phloretin or [6]-gingerol supplementation significantly reduced plasma glucose, alanine aminotransferase, aspartate aminotransferase, AGEs and insulin levels. Phloretin and [6]-gingerol also decreased the levels of AGEs and CML levels, via Nrf2 pathway, enhancing GSH/GSSG ratio, heme oxygenase-1 and glyoxalase 1 in liver tissue. These results suggest that phloretin and [6]-gingerol are potential dietary compounds that can alleviate diabetes-induced complications.

Keywords: Advance glycation end-products; CML; GSH; Nrf2; Phloretin; RAGE; [6]-Gingerol.

MeSH terms

  • Animals
  • Diet, High-Fat
  • Glucose / metabolism*
  • Glycation End Products, Advanced
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / metabolism
  • Male
  • Malus / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / genetics*
  • NF-E2-Related Factor 2 / metabolism*
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Zingiber officinale / chemistry*


  • Glycation End Products, Advanced
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Glucose