Stevens Jan F, Miranda Cristobal L, Frei Balz, Buhler Donald R
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-7301, USA.
Chem Res Toxicol. 2003 Oct;16(10):1277-86. doi: 10.1021/tx020100d.
Prenylated 2'-hydroxychalcones and flavanones from the inflorescences of the female hop plant (Humulus lupulus) were shown to inhibit peroxynitrite-mediated oxidation of low-density lipoproteins (LDL) at low micromolar concentrations. LDL oxidation was induced by the peroxynitrite generator, 3-morpholinosydnonimine (SIN-1), and measured by the formation of conjugated dienes and thiobarbituric reactive substances. Human intake of prenylated chalcones and flavanones is mainly through beer, which contains up to 4 mg/L of these polyphenols. The two main oxidation products obtained by SIN-1 and peroxynitrite treatment of xanthohumol (XN), the principal prenylflavonoid of hops, were the aurone, auroxanthohumol (AUXN), and an endoperoxy derivative of XN, named endoperoxyxanthohumol (EPOX). In addition, the reaction produced smaller amounts of the nitro and nitroso derivatives of XN and EPOX. The formation of these nitrated products was enhanced in the presence of sodium bicarbonate (25 mM). SIN-1-induced formation of AUXN is considered to be a superoxide-mediated reaction, while the structure of EPOX points to a two electron oxidation reaction involving a Michael type addition with peroxynitrite as the nucleophile, followed by cyclization yielding a (1,2)-dioxepin-5-one ring structure. The flavanone isomer of XN, isoxanthohumol (IsoXN), unexpectedly showed a slight prooxidant effect instead of an inhibitory effect on LDL oxidation. Except for the formation of minor nitrated products, IsoXN remained largely unmodified upon treatment with SIN-1/peroxynitrite. Taken together, our results suggest that the alpha,beta-unsaturated keto functionality of chalcones is most reactive toward superoxide and peroxynitrite anions.
研究表明，来自雌性啤酒花植物（啤酒花）花序的异戊烯基化2'-羟基查耳酮和黄烷酮在低微摩尔浓度下可抑制过氧亚硝酸盐介导的低密度脂蛋白（LDL）氧化。LDL氧化由过氧亚硝酸盐发生器3-吗啉代辛二亚胺（SIN-1）诱导，并通过共轭二烯和硫代巴比妥酸反应性物质的形成来测定。人类摄入异戊烯基化查耳酮和黄烷酮主要通过啤酒，啤酒中这些多酚的含量高达4mg/L。啤酒花的主要异戊烯基黄酮黄腐酚（XN）经SIN-1和过氧亚硝酸盐处理后得到的两种主要氧化产物是噢哢、金黄腐酚（AUXN），以及XN的一种内过氧化物衍生物，称为内过氧黄腐酚（EPOX）。此外，该反应还生成了少量的XN和EPOX的硝基和亚硝基衍生物。在碳酸氢钠（25 mM）存在下，这些硝化产物的形成会增加。SIN-1诱导AUXN的形成被认为是超氧化物介导的反应，而EPOX的结构表明这是一个双电子氧化反应，涉及以过氧亚硝酸盐为亲核试剂的迈克尔型加成，随后环化生成（1,2）-二氧杂环庚烷-5-酮环结构。XN的黄烷酮异构体异黄腐酚（IsoXN）出人意料地显示出轻微的促氧化作用，而不是对LDL氧化的抑制作用。除了形成少量的硝化产物外，IsoXN在用SIN-1/过氧亚硝酸盐处理后基本未发生变化。综上所述，我们的结果表明，查耳酮的α，β-不饱和酮官能团对超氧化物和过氧亚硝酸盐阴离子最具反应性。
