5-O-Demethylnobiletin, a polymethoxylated flavonoid, from Citrus depressa Hayata peel prevents protein glycation

Advanced glycation end products (AGEs) have been implicated in many age-related chronic diseases and the search for AGEs has intensified. In the present study, eight Okinawan edible or medicinal plants were screened for the anti-glycation activity. A known polymethoxylated flavonoid, 5-O-demethyl nobiletin (DN), was isolated from the chloroform fraction of Citrus depressa Hayata (Rutaceae) and was identified for the first time as an AGEs inhibitor. DN prevented protein glycation significantly better than aminoguanidine (AG) with the respective IC50 values of 64.2 and 484.3 µM (p = 0.01). Further studies revealed that DN prevented AGEs formation predominantly by inhibiting fructosamine adduct formation while only partly by preventing dicarbonyl generation. Together, these results suggest that further exploration on the identification of AGEs inhibitors from Okinawan plants and in-depth investigations on the AGEs inhibitions by polymethoxylated flavonoids are required.