High antiallergic activity of 5,6,4′-trihydroxy-7,8,3′-trimethoxyflavone and 5,6-dihydroxy-7,8,3′,4′-tetramethoxyflavone from eau de cologne mint (Mentha x piperita citrata)

The following compounds with higher antiallergic activities were isolated from eau de cologne mint leaves: 5,6,4'-trihydroxy-7,8-dimethoxyflavone (6), 5,6,4'-trihydroxy-7,8,3'-timethoxyflavone (7), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (8), 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone (9), and 5,6-dihydroxy-7,8,4'-trimethoxyflavone (10). The IC50 values of compounds 6-10 against RBL-2H3 cells were 6.7, 2.4, 5.6, 3.0, and 6.1 mu M. Compounds 7 and 9 (IC50 2.4 mu M and 3.0 mu M) had the highest antiallergic activities among the flavonoids previously reported. The amounts of 7, 9, and 10 isolated were fairly high, at 177.7 mg/kg, 278.0 mg/kg, and 179.7 mg/kg in the mint, respectively. LD5 value (index of toxicity) and LD5/IC50 ratio of 7 and 9 indicate that the safety is greater than that of luteolin, a typical antiallergic substance. The extract containing powerful antiallergic flavones, 6-10 with higher hydrophobicity could be selectively separated from the extract containing luteolin and other flavonoid glycosides by partition with dichloromethane and water. Therefore, compounds 7 and 9 in mint, and the dichloromethane extract would be the most potent and preventive resources against type I allergy. (C) 2015 Elsevier B.V. All rights reserved.