Muscadine Nutraceutical Extract Inhibits Aldose Reductase Activity to Prevent AGE Formation

Muscadines are berries of Vitis Rotundifolia , a grape native to SE USA. Muscadine skins and seeds are sold as nutraceutical products because of their high antioxidant activity, anti‐inflammatory and anti‐cancer phytochemical profiles. Hyperglycemia leads to both induction and activation of aldose reductase (AR), the initial rate‐limiting enzyme of the polyol pathway (conversion of glucose to sorbitol to fructose). Activation of the polyol pathway contributes to AGE (Advanced Glycation Endproduct) formation in organs with AR activity including lens of the eye, kidney, heart, nerves and liver. This pathway is implicated in diabetic cataract formation and neuropathies. Because the pharmacognosy of muscadine skins revealed many compounds with anti‐AR activity, we tested the ability of a muscadine skin extract to inhibit human recombinant AR in vitro . Ethanol was removed from a 1:2 (wt/v) 50% ethanolic extract of muscadine skins. Water was then removed by freeze‐drying. A dose/response relationship for inhibition of AR was established using various dilutions of the dried extract of muscadine skins. Complete AR inhibition occurred at 1:40 dilution, with the IC50 at approximately 1: 800 dilution of dried extract. Conclusion An extract of muscadine skins inhibited AR activity at high dilution. Nutraceutical products made from muscadine skins may prove useful in inhibiting AGE formation via inhibition of the polyol pathway as well as by direct inhibition of glycation (see Farrar et al., muscadine abstract this meeting). Funded by GA's Traditional Industries/ Food Processing Advisory Council Program