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

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.

Angiotensin‐(1‐7), the product of ACE2 ameliorates NAFLD by acting through its receptor Mas to regulate hepatic mitochondrial function and glycolipid metabolism

“…Here, we further verified the IRS1/Akt signaling plays key roles in AMPK activation in Mas‐overexpressed HepG2 cells (Figure 7C). This phenomenon is consistently found in human umbilical vein endothelial cells (HUVECs) and macrophage foam cells as well as in glomerular mesangial cells 47‐49 . Apart from this, it was well documented that increased Ang‐(1‐7) could activate the AMPK signaling cascade through the upregulation of adiponectin level which is regarded as the strong activator of AMPK, also via the adiponectin‐independent pathway 50‐52 .…”

“…This phenomenon is consistently found in human umbilical vein endothelial cells (HUVECs) and macrophage foam cells as well as in glomerular mesangial cells. [47][48][49] Apart from this, it was well documented that increased Ang-(1-7) could activate the AMPK signaling cascade through the F I G U R E 6 Ang-(1-7) targeting Mas receptor enhances mitochondrial function and alleviates apoptosis. A-C, Analysis of intracellular glycogen, TG, and TC contents in Ang-(1-7)-and Ang-(1-7) + A779-treated cells, with/without H 2 O 2 stimulation.…”

Nutritional Aspects of Ecologically Relevant Phytochemicals in Ruminant Production

“…The bitter-taste, emulsifying, foaming, non-ionic, non-volatile, membranolytic, surfactant, and structurally diverse saponins (glycosides) are low molecular weight (1,000–1,500 Da) secondary natural compounds in food and non-food plants ( 107 – 109 ), marine plants ( 110 ) and animal lineages, including invertebrate sea cucumber species ( 111 , 112 ). Chemically, glycoside saponin biosynthesis begins with the catalyzation of acetyl co-enzyme A to isopentenyl pyrophosphate units generated by the multistep mevalonate 3-hydroxy-3-methylglutaryl-CoA reductase ( 113 ), a common route to the synthesis of cholesterol and some steroids ( 114 ).…”

“…Although paths for those roles are not well-understood and despite differences in chemical structures, different activities exist for TPS, including adjuvant ( 136 ), antibacterial ( 137 , 138 ), antidiabetic ( 139 ), antifungal ( 140 – 142 ), anti-inflammatory ( 123 , 125 ), antioxidative ( 109 , 143 ), antiprotozoal ( 144 – 146 ), antiproliferative ( 147 ), antiviral ( 148 , 149 ), cardiotonic and cardioprotective ( 122 ), and cytotoxic ( 127 , 128 , 150 ) effects have been reported. Additionally, TPS have also exhibited other functional properties, such as food-additive in flavorings ( 26 ), gastroprotective ( 151 , 152 ), hemolytic ( 153 ), hepatic ( 139 , 149 ), immunologic ( 123 , 154 ), insecticide ( 155 , 156 ), anti-obesity therapeutic potential ( 111 , 116 , 157 , 158 ), neuroprotective ( 159 ), vermicide ( 160 ), and emulsifier and stabilizer of the nanosuspensions ( 161 , 162 ).…”

Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances

“…This is because desHA regulates the concentration of HMG-CoA reductase and NOS by blocking the LXR/AKT/AMPK pathway. Thus, desHA plays an important role in inhibiting intracellular cholesterol synthesis and promoting intracellular cholesterol outflow [181]. In addition, SCSs reduce the levels of TG, TC and LDL-C in serum of mice and rats [179,182,183] and increase the levels of HDL-C [181].…”