Inhibitors of 15-Lipoxygenase from Orange Peel

A series of polymethoxylated flavonoids has been isolated from orange peel, and their inhibitory activity toward soybean 15-lipoxygenase was determined. The strongest inhibition was shown by 3,5,6,7,3‘,4‘-hexamethoxyflavone (IC50 = 49 ± 5 μM). Sinensetin, nobiletin, tangeretin, tetramethylscutellarein, and 3,5,6,7,8,3‘,4‘-heptamethoxyflavone were somewhat less active, with IC50 values of 70−86 μM, comparable to the positive control quercetin (IC50 = 68 ± 5 μM). Demethylation apparently results in less active compounds, with 5-O-demethylsinensetin having an IC50 value of 144 ± 10 μM. Some other orange peel constituents were isolated and tested as well, hesperidin (IC50 = 180 ± 10 μM) and ferulic acid (111 ± 2 μM), showing moderate activity. The polymethoxylated flavonoids were virtually inactive as scavengers of the diphenylpicrylhydrazyl radical. Hesperidin was only slightly active (24.2 ± 0.7% scavenged at a concentration of 2 mM), and ferulic acid showed good activity (IC50 = 86.4 ± 0.7 μM). From this, it appears that orange peel constituents may counteract enzymatic lipid peroxidation processes catalyzed by 15-lipoxygenase in vitro. The radical scavenging activity of orange peel extracts is only modest. Keywords: Citrus sinensis; orange peel; flavonoids; 15-lipoxygenase; radical scavengers