Novel nitric oxide and superoxide generation inhibitors, persenone A and B, from avocado fruit.

One known, (2R)-(12Z,15Z)-2-hydroxy-4-oxoheneicosa-12,15-dien-1-yl acetate (1), and two novel compounds, persenone A (2) and B (3), have been isolated from avocado fruit (Persea americana P. Mill), as inhibitors of superoxide (O2-) and nitric oxide (NO) generation in cell culture systems. They showed marked inhibitory activities toward NO generation induced by lipopolysaccharide in combination with interferon-γ in mouse macrophage RAW 264.7 cells. Their inhibitory potencies of NO generation (1, IC50 = 3.6; 2, IC50 = 1.2; and 3, IC50 = 3.5 μM) were comparable to or higher than that of a natural NO generation inhibitor, docosahexaenoic acid (DHA; IC50 = 4.3 μM). Furthermore, compounds 1−3 and DHA markedly suppressed tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced O2- generation in differentiated human promyelocytic HL-60 cells (1, IC50 = 33.7; 2, IC50 = 1.4; 3, IC50 = 1.8; and DHA, IC50 = 10.3 μM). It is notable that they were found to be suppressors of both NO- and O2--generating biochemical pa...