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

- Phloretin and [6]-gingerol found in apple and ginger were effective in controlling CML, GSH/GSSG and total AGE levels.
- Phloretin and [6]-gingerol influenced expression of RAGE, HO-1, via Nrf2, hypothetically proposing their mechanism of action.
- Phloretin and [6]-gingerol clearly show structure-function based activity in eliminating AGEs.

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 17 weeks. 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.