Function of Thelenota ananas saponin desulfated holothurin A in modulating cholesterol metabolism

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.