Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
School of Food Science and Technology, Dalian Polytechnic University, National Engineering Research Center of Seafood, Dalian, 116034, China.
Sci Rep. 2018 Jun 22;8(1):9506. doi: 10.1038/s41598-018-27932-x.
This work was designed to separate and purify the saponin from Thelenota ananas with the highest anti-cholesterol ability using multiple chromatography and mass spectrometry analyses, and to systematically investigate the effect of the Thelenota ananas saponin on cholesterol metabolism in oxidized low-density lipoprotein (ox-LDL) induced macrophage foam cells. Desulfated holothurin A (desHA), which was finally identified as the targeted saponin with the highest activity in decreasing low-density lipoprotein-cholesterol (LDL-C), markedly inhibited the formation of foam cells derived from macrophages based on Oil Red O staining. In addition, desHA significantly blocked the synthesis of fatty acid synthetase while promoted intracellular cholesterol efflux. Furthermore, desHA inhibited the effects of ox-LDL on macrophage mRNA expression, which enhanced the level of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and suppressed the expression of SR-BI, ABCA1 and ABCG1, which further increased the levels of extracellular cholesterol and triglyceride. Blocking AKT and AMPK pathway and LXR synthesis revealed that desHA also regulated the contents of HMG-CoAR and eNOS via LXR/AKT/AMPK pathway. Thus, desHA played an essential role in cholesterol efflux and synthesis, which indicated desHA and Thelenota ananas are valuable resources to exploit new functional food and nutraceuticals.
本研究旨在利用多种色谱和质谱分析方法从菠萝海鞘中分离和纯化具有最高降胆固醇能力的皂苷，并系统研究菠萝海鞘皂苷对氧化型低密度脂蛋白（ox-LDL）诱导的巨噬细胞泡沫细胞胆固醇代谢的影响。最终鉴定出具有最强降低 LDL-C 活性的目标皂苷为去硫酸海参素 A（desHA），它可显著抑制巨噬细胞来源泡沫细胞的形成，这基于油红 O 染色结果。此外，desHA 可显著抑制脂肪酸合酶的合成，同时促进细胞内胆固醇流出。此外，desHA 抑制 ox-LDL 对巨噬细胞 mRNA 表达的作用，从而提高 3-羟基-3-甲基戊二酰基辅酶 A 还原酶（HMG-CoAR）的水平，并抑制 SR-BI、ABCA1 和 ABCG1 的表达，这进一步增加了细胞外胆固醇和甘油三酯的水平。阻断 AKT 和 AMPK 通路和 LXR 合成表明，desHA 还通过 LXR/AKT/AMPK 通路调节 HMG-CoAR 和 eNOS 的含量。因此，desHA 在胆固醇流出和合成中发挥了重要作用，这表明 desHA 和菠萝海鞘是开发新型功能性食品和营养保健品的有价值资源。
