Inhibitory Effect of 6-gingerol on Fructose-Mediated Protein Glycation in Vitro

        Background: High fructose comsumption is associated with the development of diabetic complication. Fructose, like other reducing sugars, can react non-enzymatically with proteins through the Maillard reaction, leading to form irreversible advanced glycation end product (AGEs). However, it is more potent in producing AGEs than glucose. AGEs formation are also accompanied by the formation of free radicals via metal ion-catalyzed autoxidation of sugar and glycated proteins. The increase in free radicals during glycation process may cause protein modifications, leading to development of diabetic complication. Therefore, the inhibition of AGEs formation may be a promising target for therapeutic intervention in these AGEs-related disorders. The aim of this study was to evaluate the inhibitory effect of 6-gingerol on fructose-mediated protein glycation and oxidation of human serum albumin (HSA).

        Methods: Antioxidant activity of 6-gingerol was assessed using ferrous iron chelating activity methods. The protein glycation inhibitory potential was evaluated using in vitro HSA/fructose model. HSA and fructose (0.5 M) were incubated at 37 C in the presence or absence of 6-gingerol (1-100 μM) for 14 days. The effect of 6-gingerol on AGEs formation was investigated by measuring AGE-specific fluorescence. In addition glycation induced protein oxidation was assessed by using the protein thiol oxidation and carbonyl assays. Results : 6-gingerol exhibited the potent metal chelation properties. The formation of fructose (0.5 M) derived AGEs was significantly decreased by 6-gingerol (1 - 100 μM) in a concentration-dependent manner. Moreover, fructose caused a significant elevation of protein carbonyl content and oxidation of thiols in glycated than in native HSA. 6-gingerol (100 μM) decreased high fructose-induced oxidative damages to protein by reducing protein carbonyl formation and preserving protein thiols from oxidation.
        Conclusion: These results suggest that 6-gingerol is capable of suppressing the formation of AGEs and protein oxidation in vitro, which might involve their metal chelating activity that inhibits glycoxidative-AGEs formation.

Keywords: 6-gingerol, glycation, advanced glycation end products, fructose