Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato, Hakodate, Hokkaido 041-8611, Japan.
Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato, Hakodate, Hokkaido 041-8611, Japan.
Arch Biochem Biophys. 2024 Oct;760:110125. doi: 10.1016/j.abb.2024.110125. Epub 2024 Aug 16.
Apocarotenoids have short carbon chain structures cleaved at a polyene-conjugated double bond. They can be biosynthesized in plants and microorganisms. Animals ingest carotenoids through food and then metabolize them into apocarotenoids. Although several apocarotenoids have been identified in the body, their precise health functions are still poorly understood. This study investigated the anti-inflammatory activities of apo-12'-capsorubinal in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. It was confirmed that apo-12'-capsorubinal was not cytotoxic to the macrophages at the concentrations tested. Apo-12'-capsorubinal treatment led to a marked downregulation of interleukin (IL)-6 protein and Il6 mRNA levels. This apocarotenoid exhibited more potent inhibitory effects than its parent carotenoids, capsanthin and capsorubin. Furthermore, apo-12'-capsorubinal, but not its parent carotenoids, promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-target genes, such as heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), in a dose-dependent manner. Furthermore, a comparison using apo-12'-zeaxanthinal and 7,8-dihydro-8-oxo-apo-12'-zeaxanthinal revealed that the α, β-unsaturated carbonyl group on the polyene linear chain mediated the enhanced nuclear Nrf2 translocation, HO-1 expression, and inhibition of IL-6 production. In contrast, apo-12'-mytiloxanthinal, which harbored a hydroxyl group at C-8 of apo-12'-capsorubinal, did not exhibit any of these activities. These results indicated that the β carbon of the α, β-unsaturated carbonyl group in the linear part of the polyene chain is crucial to the Nrf2-activating and anti-inflammatory effects of apo-12'-capsorubinal. This study will advance our knowledge of the physiological significance of xanthophyll-derived apocarotenoids and their potential use as nutraceuticals and pharmaceuticals.
类胡萝卜素具有在多烯共轭双键处断裂的短碳链结构。它们可以在植物和微生物中生物合成。动物通过食物摄取类胡萝卜素，然后将其代谢为类胡萝卜素。尽管已经在体内鉴定出几种类胡萝卜素，但它们的确切健康功能仍知之甚少。本研究探讨了脂多糖（LPS）刺激的 RAW264.7 巨噬细胞中脱辅基-12'-辣椒红素的抗炎活性。结果证实，在所测试的浓度下，脱辅基-12'-辣椒红素对巨噬细胞没有细胞毒性。脱辅基-12'-辣椒红素处理导致白细胞介素（IL）-6 蛋白和 Il6 mRNA 水平显著下调。与母体类胡萝卜素辣椒红素和辣椒玉红素相比，这种类胡萝卜素表现出更强的抑制作用。此外，脱辅基-12'-辣椒红素（而非母体类胡萝卜素）促进核因子红细胞 2 相关因子 2（Nrf2）的核积累，并上调 Nrf2 靶基因的表达，如血红素加氧酶 1（HO-1）和 NAD（P）H：醌氧化还原酶 1（NQO-1），呈剂量依赖性。此外，使用脱辅基-12'-玉米黄质和 7,8-二氢-8-氧代脱辅基-12'-玉米黄质进行比较表明，多烯线性链上的α，β-不饱和羰基介导了增强的核 Nrf2 易位、HO-1 表达和抑制 IL-6 产生。相比之下，脱辅基-12'-岩藻黄质，其在脱辅基-12'-辣椒红素的 C-8 位上含有一个羟基，没有表现出任何这些活性。这些结果表明，多烯链线性部分的α，β-不饱和羰基的β 碳原子对于脱辅基-12'-辣椒红素的 Nrf2 激活和抗炎作用至关重要。本研究将提高我们对叶黄素衍生类胡萝卜素的生理意义及其作为营养保健品和药物的潜在用途的认识。
