Abstract
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.
Highlights
Saponins are the primary glycosylated secondary metabolites found in many major crops and certain sea foods, such as the sea cucumber, starfish and alcyonacea[1]
The results of the high performance liquid chromatography (HPLC)-mass spectroscopy (MS) analyses revealed that the molecular mass of compound 3 is 1119 Da, which is the same with desulfated holothurin A (NCBI PubChem CID: 3038027, CAS NO. 11060-73-4, Desulfated holothurin A (desHA))
DesHA has been previously detected in sea cucumber Holothuria forskali, known as nobiliside 2A23
Summary
Saponins are the primary glycosylated secondary metabolites found in many major crops and certain sea foods, such as the sea cucumber, starfish and alcyonacea[1]. Active compositions of sea cucumber saponins have been clarified by using silica-gel column chromatography, high performance liquid chromatography (HPLC) and high performance centrifugal partition chromatography (HPCPC) and other newly developed technologies, including holothurin A1 (HA), holothurin B (HB), 24-dehydroechinoside A (DA), echinoside A (EA), argusides, coustesids, holothurinosides, impatiensides, marmoratoside A and philinopsides[2,3,4,5,6,7,8,9,10]. The objective of the study was to screen and identify the Thelenota ananas saponin with the highest activity of lowering cholesterol. Saponin in modulating cholesterol metabolism in vitro, which may provide further theoretical support regarding the anti-atherosclerotic role of Thelenota ananas saponin
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