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Int J Mol Sci. 2022 Jun 23;23(13):6953. doi: 10.3390/ijms23136953.
Low levels of n-3 poly-unsaturated fatty acids (n-3 PUFAs) and high levels of n-6 PUFAs in the blood circulation are associated with an increased risk for suicide. Clinical studies indicate that docosahexaenoic acid (DHA, a n-3 PUFA found in fish-oil) displays protective effects against suicide. It has recently been proposed that the activation of the transcription factor NRF2 might be the pharmacological activity that is common to current anti-suicidal medications. Oxidation products from fish oil, including those from DHA, are electrophiles that reversibly bind to a protein 'KEAP1', which acts as the molecular inhibitor of NRF2 and so indirectly promotes NRF2-transcriptional activity. In the majority of publications, the NRF2-stimulant effect of DHA is ascribed to the metabolite 4-hydroxyhexenal (4HHE). It is suggested to investigate whether 4HHE will display a therapeutically useful anti-suicidal efficacy.
血液中 n-3 多不饱和脂肪酸（n-3 PUFA）水平较低和 n-6 PUFA 水平较高与自杀风险增加有关。临床研究表明，二十二碳六烯酸（DHA，一种存在于鱼油中的 n-3 PUFA）对自杀具有保护作用。最近有人提出，转录因子 NRF2 的激活可能是目前抗自杀药物共有的药理学活性。来自鱼油的氧化产物，包括 DHA 的氧化产物，是一种亲电试剂，可可逆地与一种名为“KEAP1”的蛋白质结合，KEAP1 作为 NRF2 的分子抑制剂，间接促进 NRF2 的转录活性。在大多数出版物中，DHA 的 NRF2 刺激作用归因于代谢产物 4-羟基己醛（4HHE）。有人建议研究 4HHE 是否会显示出治疗上有用的抗自杀疗效。
