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 muM) Sinensetin, nobiletin, tangeretin, tetramethylscutellarein, and 3,5,6,7,8,3',4'-heptamethoxyflavone were somewhat less active, with IC50 values of 70-86 muM, comparable to the positive control quercetin (IC50 = 68 +/- 5 muM). Demethylation apparently results in less active compounds, with 5-O-demethylsinensetin having an IC50 value of 144 +/- 10 muM Some other orange peel constituents were isolated and tested as well, hesperidin (IC50 = 180 +/- 10 muM) and ferulic acid (111 +/- 2 muM), 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 muM) 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.