Novel Nitric Oxide and Superoxide Generation Inhibitors, Persenone A and B, from Avocado Fruit
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One known, (2R)-(12Z,15Z)-2-hydroxy-4-oxoheneicosa-12,15-dien-1-yl acetate (1), and two novelcompounds, 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 incombination with interferon- in mouse macrophage RAW 264.7 cells. Their inhibitory potencies ofNO generation (1, IC50 = 3.6; 2, IC50 = 1.2; and 3, IC50 = 3.5 M) were comparable to or higherthan that of a natural NO generation inhibitor, docosahexaenoic acid (DHA; IC50 = 4.3 M).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 M). It is notable that they werefound to be suppressors of both NO- and O2--generating biochemical pathways but not to be radicalscavengers. The results indicate that these compounds are unique antioxidants, preferentiallysuppressing radical generation, and thus may be promising as effective chemopreventive agentcandidates in inflammation-associated carcinogenesis.Keywords: Cancer chemoprevention; nitric oxide; superoxide; avocado; RAW 264.7 cells; HL-60cells

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