Apple phlorizin reduce plasma cholesterol by down-regulating hepatic HMG-CoA reductase and enhancing the excretion of fecal sterols

This study was aimed to examine the effect of apple phlorizin on lipid accumulation in HepG2 cell and hamsters (Thirty-six male Golden Syrian hamsters) fed with atherogenic diet. Dietary supplementation of 0.9% phlorizin significantly decreased the level of plasma total cholesterol (TC), triacylglycerols (TG), activity of cholesteryl ester transfer protein (CETP) and liver 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA-R), alongside down-regulated the gene expressions of intestinal Niemann-Pick C1-like 1 (NPC1L1), HMG-CoA-R and up-regulated ATP-binding cassette transporters subfamily G members 5/8 (ABCG5/8) gene. Phlorizin increased the excretion of sterols, reduce absorption of dietary cholesterol and de novo synthesis of cholesterol. Furthermore, in silico studies revealed the binding profile of the phlorizin and HMG-CoA-R, hinted at the molecular interactions that are responsible for its activity. These results suggested that dietary supplementation of phlorizin could potentially possess cholesterol-lowering activity by increasing the excretion of sterols and mediating the endogenous cholesterol metabolic management.Graphical abstract
Source: Journal of Functional Foods - Category: Nutrition Source Type: research

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In this study, we found that CSFV replication before fusion was affected when the cholesterol trafficking in infected cells was disrupted using a cholesterol transport inhibitor, U18666A. Our data showed that U18666A affected both the fusion and replication steps in the life cycle of the virus, but not its binding and entry steps. The subsequent experiments confirmed that niemann-pick C1 (NPC1), a lysosomal membrane protein that helps cholesterol to leave the lysosome, was affected by U18666A, which led to the accumulation of cholesterol in lysosomes and inhibition of CSFV replication. Imipramine, a cationic hydrophobic am...
Source: Veterinary Microbiology - Category: Veterinary Research Source Type: research
Unesterified cholesterol accumulation in the late endosomal/lysosomal (LE/LY) compartment is the cellular hallmark of Niemann-Pick C (NPC) disease, caused by defects in the genes encoding NPC1 or NPC2. We previously reported the dramatic stimulation of NPC2 cholesterol transport rates to and from model membranes by the LE/LY phospholipid lysobisphosphatidic acid (LBPA). It had been previously shown that enrichment of NPC1-deficient cells with LBPA results in cholesterol clearance. Here we demonstrate that LBPA enrichment in human NPC2-deficient cells, either directly or via its biosynthetic precursor phosphtidylglycerol (P...
Source: eLife - Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cell Biology Source Type: research
Discussion of Developmental Effects on Aging Microtubule Function and Longevity in Nematodes Quantifying the Correlation Between Poverty and Faster Pace of Aging Matthew O'Connor Presenting on Underdog Pharmaceuticals at Undoing Aging 2019 https://www.fightaging.org/archives/2019/09/matthew-oconnor-presenting-on-underdog-pharmaceuticals-at-undoing-aging-2019/ Here Matthew O'Connor of the SENS Research Foundation talks about the research that led to founding of Underdog Pharmaceuticals, a biotech startup incubated by the foundation to commercialize a means of targeting 7-ketocholesterol in atheroscleros...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Microalgae are photosynthetic microorganisms that produce numerous bioactive molecules that can be used as food supplement to prevent chronic disease installation. Indeed, they produce phycobiliproteins, polysaccharides, lipids, carotenoids and sterolic compounds. The use of microalgae in human nutrition provide a mixture of these molecules with synergistic effect. The aim of this review is to present the specific roles played by the xanthophylls, and specifically astaxanthin and fucoxanthin, two high added value carotenoids, and by microalgal phytosterols such as β-sitosterol, campesterol and stigma...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research
Here Matthew O'Connor of the SENS Research Foundation talks about the research that led to founding of Underdog Pharmaceuticals, a biotech startup incubated by the foundation to commercialize a means of targeting 7-ketocholesterol in atherosclerosis and other conditions. Oxidized cholesterols, and largely 7-ketocholesterol, are the primary cause of dysfunction in the macrophage cells normally responsible for preventing the build up of fatty plaques in blood vessel walls. That dysfunction is the cause of atherosclerosis, and the fact that the presence of oxidized cholesterols increases with age is one of the reasons why ath...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
Publication date: Available online 12 September 2019Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Daniel Petersen, Peter Reinholdt, Maria Szomek, Selina Kruuse Hansen, Vasanthanathan Poongavanam, Alice Dupont, Christian W. Heegaard, Kathiresan Krishnan, Hideji Fujiwara, Douglas F. Covey, Daniel S. Ory, Jacob Kongsted, Daniel WüstnerAbstractSide-chain oxidized cholesterol derivatives, like 25-hydroxycholesterol (25-OH-Chol) are important regulators of cellular cholesterol homeostasis. How transport of oxysterols through the endo-lysosomal pathway contributes to their biological function is not cl...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research
Publication date: 24–30 August 2019Source: The Lancet, Volume 394, Issue 10199Author(s): Kausik K Ray, Pablo Corral, Enrique Morales, Stephen J NichollsSummaryAtherosclerosis and its clinical manifestation as ischaemic heart disease remains a considerable health burden. Given that many factors contribute to ischaemic heart disease, a multifactorial approach to prevention is recommended, starting with lifestyle advice, smoking cessation, and control of known cardiovascular risk factors, such as blood pressure and lipids. Within the lipid profile, the principal target is lowering LDL cholesterol, firstly with lifestyle...
Source: The Lancet - Category: General Medicine Source Type: research
In this study, we sought to define the structure of an unknown lipid biomarker for NPC1 with [M + H]+ ion at m/z 509.3351, previously designated as lysoSM-509. The structure of N-palmitoyl-O-phosphocholineserine (PPCS) was proposed for the lipid biomarker based on the results from mass spectrometric analyses and chemical derivatizations. As no commercial standard is available, authentic PPCS was chemically synthesized, and the structure was confirmed by comparison of endogenous and synthetic compounds as well as their derivatives using liquid chromatography-tandem mass spectrometry (LC-MS/MS). PPCS is the most abundant spe...
Source: The Journal of Lipid Research - Category: Lipidology Authors: Tags: Research Articles Source Type: research
Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disease (1 per 100 000 newborns) caused by NPC proteins impairment that leads to unesterified cholesterol accumulation in late endosomal/lys...
Source: BMC Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Research article Source Type: research
Abstract The dyshomeostasis of intracellular cholesterol trafficking is typical of the Niemann-Pick type C (NPC) disease, a fatal inherited lysosomal storage disorder presenting with progressive neurodegeneration and visceral organ involvement. In light of the well-established relevance of cholesterol in regulating the endocannabinoid (eCB) system expression and activity, this study was aimed at elucidating whether NPC disease-related cholesterol dyshomeostasis affects the functional status of the brain eCB system. To this end, we exploited a murine model of NPC deficiency for determining changes in the expression...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
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