Numerous benefits have been attributed to dietary long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs), including protection against cardiac arrhythmia, triglyceride-lowering, amelioration of inflammatory, and neurodegenerative disorders. This review covers recent findings indicating that a variety of these beneficial effects are mediated by “omega-3 epoxyeicosanoids”, a class of novel n-3 LC-PUFA-derived lipid mediators, which are generated via the cytochrome P450 (CYP) epoxygenase pathway. CYP enzymes, previously identified as arachidonic acid (20:4n-6; AA) epoxygenases, accept eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA), the major fish oil n-3 LC-PUFAs, as efficient alternative substrates. In humans and rodents, dietary EPA/DHA supplementation causes a profound shift of the endogenous CYP-eicosanoid profile from AA- to EPA- and DHA-derived metabolites, increasing, in particular, the plasma and tissue levels of 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP). Based on preclinical studies, these omega-3 epoxyeicosanoids display cardioprotective, vasodilatory, anti-inflammatory, and anti-allergic properties that contribute to the beneficial effects of n-3 LC-PUFAs in diverse disease conditions ranging from cardiac disease, bronchial disorders, and intraocular neovascularization, to allergic intestinal inflammation and inflammatory pain. Increasing evidence also suggests that background nutrition as well as genetic and disease state-related factors could limit the response to EPA/DHA-supplementation by reducing the formation and/or enhancing the degradation of omega-3 epoxyeicosanoids. Recently, metabolically robust synthetic analogs mimicking the biological activities of 17,18-EEQ have been developed. These drug candidates may overcome limitations of dietary EPA/DHA supplementation and provide novel options for the treatment of cardiovascular and inflammatory diseases.

膳食长链omega-3多不饱和脂肪酸（n-3 LC-PUFAs）带来了许多好处，包括预防心律不齐，降低甘油三酸酯，减轻炎症和神经退行性疾病。这篇综述涵盖了最近的发现，这些发现表明“ omega-3环氧二十烷酸”是一类新型的n-3 LC-PUFA衍生的脂质介体，通过细胞色素P450（CYP）环氧合酶途径产生，介导了多种有益作用。 。CYP酶以前被鉴定为花生四烯酸（20：4n-6; AA）环氧酶，可以接受二十碳五烯酸（20：5n-3; EPA）和二十二碳六烯酸（22：6n-3; DHA），主要的鱼油是n- 3种LC-PUFA，作为有效的替代底物。在人类和啮齿动物中，饮食中EPA / DHA的添加会导致内源性CYP-类花生酸的分布从AA-转变为EPA和DHA衍生的代谢产物，尤其是增加血浆和组织中17,18-环氧二十碳四烯酸（17,18- EEQ）和19,20-环氧二十二碳五烯酸（19,20-EDP）。根据临床前研究，这些omega-3环氧类二十烷酸类药物具有心脏保护，血管舒张，抗炎和抗过敏的特性，这些特性有助于n-3 LC-PUFA在心脏病，支气管疾病和各种疾病的多种疾病中的有益作用。眼内新血管形成，可引起过敏性肠炎和炎性疼痛。越来越多的证据还表明，背景营养以及与遗传和疾病状态相关的因素可能会通过减少omega-3环氧类二十烷酸的形成和/或增强其降解而限制对EPA / DHA补充的反应。近来，已经开发出模仿17，18-EEQ的生物学活性的代谢健壮的合成类似物。这些候选药物可以克服饮食中EPA / DHA补充剂的局限性，并为心血管疾病和炎性疾病的治疗提供新的选择。