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Spelt, an ancient bread cereal, is being rediscovered in Europe and North America, mainly because it is said to have valuable nutritional and/or physiological properties, although the scientific basis of such claims have not yet been established. Previous studies have shown that spelt fine bran has a higher lipid content (including phytosterols) than wheat’s corresponding fraction. Since phytosterols are able to exert a hypercholesterolemia effect when given as dietary supplement, the aims of the study were :
1. To evaluate the effects of spelt versus wheat fine bran on lipid metabolism
2. To compare the physiological effects of two different doses of phytosterols on this metabolism and
3. To analyse the direct effects of the main phytosterol present en bran on hepatic lipid synthesis. In first experiment, male Wistar rats were fed either a standard diet (A04) or the same diet enriched with 0,4 % cholesterol, 0,4 % cholesterol + 10 % wheat fine bran. After4 weeks, when compared with rats fed with a standard diet, cholesterol addition increased the hepatic cholesterol and triglycerides content. No difference in hepatic lipids resulted from fine bran addition of either cereal; serum cholesterol was even higher in wheat treated animals, probably due to the higher daily dietary intake. In the second experiment, rat received a standard diet, 4,4 % cholesterol + 0,05 % phytosterols or 0,4% cholesterol + 1 % phytosterols.
All the protocol was similar to the first one. The food conversion efficiency (FCE) was clearly inferior when phytostérols were present in the diet. Furthermore, 1 % phytosterol seems to be necessary and enough to avoid the hepatic accumulation of the dietary cholesterol.
Nevertheless, we did not notice any significant reduction of blood lipid levels even if LDL-C was lower phytosterol were given.
On the other hand, the main phytosterol of spelt fine bran, , namely β-sitosterol, reduced cholesterol synthesis-measured as labelled acetate incorporation into cholesterol inside PCLS (Precision Cut Liver Slices) in culture – when added to the culture medium of PCLS at the dose of 50 Μm. No cell toxicity was noted at this dose.
Our results suggest that, in addition to the well-known interference with intestinal cholesterol absorption, β-sitosterol reduces, in vitro, the cholesterol synthesis in PCLS; but in our experimental conditions, no effect of spelt fine bran could be shown on lipid metabolism in cholesterol fed rats. This may be explained by the fact that phytosterol content in spelt fine bran remains to allow any intestinal or hepatic L’épeautre, cousin éloigné du froment et tout comme lui planifiable, connaît à l’heure actuelle un regain d’intérêt en Europe et aux Etats-Unis. On lui accorde de nombreuses propriétés physiologiques et/ou nutritionnelles, sans qu’aucune d’entre elles ne soient encore scientifiquement établie.
Des études préalables montrent que le fin son gris de farine d’épeautre est plus riche en lipides (y compris en phytostérols) que le sous-produit correspondant de froment. Par ailleurs, les phytostérols sont capables d’exercer un effet hypocholestérolémiant lorsqu’ils sont donnés comme suppléments alimentaires.
Dans une première étude, nous avons évalué l’effet du fin son gris de farine d’épeautre (EP) par rapport à celui de froment (FR) sur le métabolisme lipidique du rat.
Des rats Wistar ont reçu une alimentation standard (A04) ou le même diète enrichie de 0,4% de cholestérol, 0,4 % de cholestérol + 10 % EP ou 0,4 % de cholestérol + 10% FR.
Après 4 semaines, l’ajout de cholestérol dans la diète a augmenté significativement le contenu hépatique en tryglycérides (TG) et cholestérol par rapport au groupe contrôle. Aucune différence du contenu hépatique en lipides n’à cependant pu être attribuée à la présence de fin son.
Les taux sanguins de TG et de cholestérol étaient plus élevés dans le groupe FR par rapport au groupe EP, tout comme la consommation alimentaire.
Une seconde étude in vivo chez le rat a permis d’étudier l’influence des phytostérols contenus dans le fin son gris d’épeautre (β-sitostérol essentiellement) sur le métabolisme lipidique.
Le protocole expérimental fut calqué sur le précédent ; les groupes contrôle et cholestérol seul étant identiques ; les 2 groupes supplémentés en phytostérols reçurent 0,4 % de cholestérol + 0,05 ou 1 % de phytostérols.
L’ajout des phytostérols dans la diète a diminué significativement la Food Conversion Efficiency (FEC) par rapport aux groupes contrôle et cholestérol seul dans la mesure où les rats supplémentés en phytostérols consommaient davantage de nourriture mais prenaient moins de poids. La quantité de 1% de phytostérols s’est avérée nécessaire et suffisante pour empêcher l’accumulation hépatique du cholestérol exogène. Toutefois, nous n’avons pas mis en évidence une baisse significative des lipides sanguins suite à la consommation de phytostérols. En outre, la synthèse hépatique du cholestérol, inhibée suite à la présence de cholestérol, n’a pu être restaurée en présence de phytostérols.
Nous avons dés lors analysé l’effet direct du β-sitostérol sur le métabolisme hépatique du cholestérol grâce au modèle des PCLS (precision-cut-liver-slices). Lorsqu’une dose de 50 μM de ce stérol est présente dans le milieu de culture des PCLS, une diminution significative de la synthèse du cholestérol, mesurée par l’incorporation d’acétate marqué au sein des PCLS en culture est observée. Nos résultats suggèrent qu’en plus de l’interférence bien établie au niveau de l’absorption du cholestérol, le β-sitostérol, notamment présent dans le fin son gris d’épeautre, module directement le métabolisme hépatique
Phytosterols --- Flour
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Cholesterol is a vital compound for humans. However higher total cholesterol levels are able to lead to important health hazards, like cardiovascular diseases (Rozner & Garti 2006). ln the case of hypercholesterolemia, a 10 % decrease of cholesterol rate in the blood reduces cardiovascular diseases risks of 19 to 54% (Quilez et al. 2003).
The aim of this master thesis is to describe succinctly the cholesterol metabolism and the health effects of this molecule. We also explained the different therapies against hypercholesterolemia and exposed the phytosterols roles in these medications.
The phytosterols are sterols that are found in vegetable species. These compounds have a structure similar to cholesterol and reduce the dietary cholesterol intake. All the mechanisms are not yet well understood, but they are well studied. Some hypotheses are suggested (Rozner & Garti 2006). The phytosterols could inhibit the cholesterol intake by competition for solubilisation in mixed micelles, by co-crystallisation to form insoluble mixed crystals in the gastrointestinal tract, by competition for pancreatic cholesterol esterases, etc (Trautwein et al. 2003, Rozner & Garti 2006). Unfortunately to obtain the 2 gr of phytosterols per day (quantity that allows a 10%reduce for the LDL rate (Brufau et al. 2008)), vegetables have to be consumed in huge amounts (1.5 kg ofwalnut or 4.5 kg of broccoli or 100 slices of wholemeal bread, etc.). So the use of enriched phytosterol foods as functional ingredient in diet seems to be a good and save option to improve the cholesterol rate in the population (Quilez et al. 2003). The main disadvantage to consume phytosterols is that they are. able to interfere with the carotenoids and vitamins intakes (Rozner & Garti 2006).
Nevertheless, the phytosterols place in hypercholesterolemia treatments is not defined yet. A lot of questions still remain. More studies are necessary to define the population for which they may give the best benefits and to measure clinically these benefits (Lecerf 2007) Le cholestérol est un composé vital pour l'Homme. Néanmoins, à des taux trop élevé, il peut mener à des complications de santé importantes, comme le développement de maladies cardio-vasculaires (Rozner & Garti 2006). Dans le cas d'hypercholestérolémie, on estime qu'une diminution de 10 % du taux de cholestérol dans le sang réduit le risque de maladies cardio-vasculaires de 19 à 54 % (Quilez et coll. 2003).
L'objectif de ce travail est de décrire succinctement le métabolisme du cholestérol et ses effets sur la santé. Nous exposerons également les différentes thérapies hypocholestérolémiantes existantes. Enfin, nous présenterons la place des phytostérols dans ces thérapies.
Les phytostérols sont des stérols présents naturellement dans les espèces végétales. Ces composés de structure similaire à celle du cholestérol réduiraient l'absorption du cholestérol alimentaire. Le mécanisme n'est pas complètement compris, mais est largement étudié et plusieurs hypothèses ont déjà été suggérées (Rozner & Garti 2006). Les phytostérols pourraient inhiber l'absorption du cholestérol par compétition de solubilisation au niveau des micelles, par co-cristallisation dans le tractus gastro-intestinal, par compétition au niveau des cholestérols estérases pancréatiques, etc. (Trautwein et coll. 2003, Rozner & Garti 2006). Malheureusement, pour consommer 2 g de stérols végétaux par jour (quantité qui permet une réduction du taux de LDL de 10% (Brufau et coll. 2008)), la quantité de certains aliments devant être consommée est considérable (1,5 kg de noix ou 4,5 kg de brocolis ou 100 tranches de pain complet, etc.). C'est pourquoi l'utilisation de phytostérols comme ingrédients fonctionnels dans l'alimentation apparaît être une option pratique et sure pour améliorer le taux de cholestérol dans la population (Quilez et coll. 2003). Le seul désavantage à la consommation de phytostérols est qu'ils peuvent interférer avec l'absorption de caroténoïdes et des vitamines (Rozner & Garti 2006).
La place des phytostérols dans l'arsenal thérapeutique de la prévention cardio- vasculaire n'est pas encore définie. De nombreuses questions restent posées. Des études complémentaires pour mieux définir les sujets qui pourraient en bénéficier et pour mesurer cliniquement leur intérêt sont nécessaires (Lecerf 2007).
Phytosterols --- Anticholesteremic Agents --- Cholesterol --- Atherosclerosis --- Dyslipidemias
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Lipoproteins --- Plant Oils --- Phytosterols --- Phenols --- blood --- pharmacology --- pharmacokinetics
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plant oils --- plant oils --- Oxidation --- Oxidation --- Colour --- Colour --- Smell --- Smell --- Organoleptic properties --- Organoleptic properties --- Purification --- Purification --- Food technology --- Food technology --- Distilling --- Distilling --- Phytosterols --- Phytosterols --- Tocopherols --- Tocopherols
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Glucans --- Tocotrienols --- Lipoproteins --- Soybean Proteins --- Phytosterols --- Sitosterols --- Cardiovascular Diseases --- pharmacology --- blood --- therapeutic use --- prevention & control
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Antioxidants --- Dietary Fats --- Plants, Edible --- Sitosterols --- Phytosterols --- Anticholesteremic Agents --- analysis --- administration & dosage --- chemistry --- pharmacology
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Sterols and other isoprenoids are of great interest for their molecular structure and function in cell architecture and evolution, as well as for their importance in medicine and agriculture. Molecules’ 2019 Festschrift Special Issue in honor of the 65th birthday of Prof. W. David Nes, an internationally recognized chemical biologist and recipient of the George Schroepher medal for sterol research, focuses on recent developments in the chemistry, biosynthesis, and function of these polycyclic natural products. This volume of Molecules contains 16 leading-edge review articles and original research contributions from an international cast of scientists. This volume is grouped into three sections: (i) isoprenoid metabolome and diversity, (ii) clinical evaluation of sterol and triterpene structures and biosynthesis, and (iii) methods and synthesis of steroids and other compounds. The volume will be a valuable reference tool for those who study medicinal chemistry, protein chemistry, and biochemistry of isoprenoid lipids.
high-fat high-carbohydrate diet --- toxicity --- oxysterol --- n/a --- squalene cyclase --- sterol content --- sterolomics --- Polystichum --- Smith-Lemli-Opitz syndrome --- antifungals --- alkaloid --- cycloartenol synthase --- degeneration --- phytosterol --- Rhizopus arrhizus --- fibroblasts --- pod-blast --- fern --- cholesterol --- cytotoxic activity --- N-methylpiperidine. reductive deamination --- genetic disease --- isoprenoid --- steroid --- atherosclerosis --- granatane --- antioxidant --- wound healing --- development --- enzyme-assisted derivatization --- maturity --- terpene --- keratinocytes --- C4-demethylation complex (C4DMC) --- ?-sitosterol --- mesocarp --- sterol biosynthesis --- mechanism-based inactivators --- Mucorales --- gas chromatography-mass spectrometry (GC-MS) --- Girard reagent --- ROS --- sterol pattern --- N-methylcadaverine --- ?-tocopherol --- electrospray ionization-mass spectrometry --- human African trypanosomiasis --- HUVECs --- lipidomics --- campesterol --- triterpene --- oxyphytosterol --- leishmania --- Chagas disease --- LOX-1 --- sterol C24-methyltransferase --- antifungal effectivity --- ergosterol biosynthesis --- hormone --- glucose homeostasis --- retina --- solanaceae --- cholestanoic acid --- algal sterols --- cell migration --- withanolides --- insulin resistance --- Zingiber officinale --- posaconazole --- synthesis --- pre-diabetes --- pharmacognosy --- sterol --- 4-methylsterol --- oleanolic acid --- antiparasitic drugs --- lupeol --- oilseed --- aurelianolides --- divalent metal co-factor ligation --- bile alcohol --- phytosterols --- azoles --- infectious disease --- gingerols --- UV-radiation --- oil bodies --- ZnO --- sterol 14?-demethylase --- stigmasterol
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Bioactive compounds and drugs are designed and screened on the basis of specific molecular targets as well as via the identification of active ingredients from traditional medicine or by serendipitous discovery. The development of novel therapeutic strategies not only requires a deep knowledge of the molecular processes and the cellular pathways involved in each pathological condition and disease, but also the specific protein targets and the effects of drug binding on protein conformation and activity. Understanding of how drugs can modify and modulate specific cellular pathways and functions will be helpful during the process of drug development and clinical trials.
Research & information: general --- Chemistry --- serum half-life extension --- fatty acid conjugation --- FcRn-mediated recycling --- serum albumin --- translocator protein (TSPO) --- CoCl2 --- mitochondrial membrane potential --- reactive oxygen species (ROS) --- cell viability --- cell death --- lung cancer cell line --- acetylcholinesterase --- amyloid beta aggregation --- neuroprotection --- molecular docking --- multi-target drug --- structure–activity relationship --- brassicasterol --- phytosterols --- HSV --- Mycobacterium tuberculosis --- HSV-1 DNA polymerase --- HSV-1 TK --- human CDK2 --- ACE --- UDP-galactopyranose mutase --- heat shock protein 70 --- Hsp70 --- piperine --- fluorescence spectroscopy --- molecular dynamics --- molecular biophysics --- GADD45β --- MKK7 --- multiple myeloma --- protein-ligand interaction --- STD-NMR --- sigma receptors --- sigma ligands --- cancer --- SIGMAR1 --- PGRMC1 --- TMEM97 --- NCI60 COMPARE analysis --- membrane --- lipid-protein interaction --- lipid signalling --- kinase regulation --- phosphatidylinositols --- molecular docking simulation --- target identification --- small-molecule derivatives of salicylanilide --- drug discovery --- drug development --- thyroid diseases --- endocrine disruptor compound --- human umbilical artery --- vascular homeostasis
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There is unequivocal experimental, epidemiological, and clinical evidence demonstrating a correlation between diet and increased risk of cardiovascular disease (CVD). While nutritionally-poor diets can have a significant negative impact on cardiovascular health, dietary interventions with specific nutrients and/or functional foods are considered cost-effective and efficient components of prevention strategies. It has been estimated that nutritional factors may be responsible for approximately 40% of all CVD. Indeed, in one of the seminal studies conducted on modifiable risk factors and heart health (the INTERHEART study), >90% of all myocardial infarctions were attributed to preventable environmental factors with nutrition identified as one of the important determinants of CVD. There is an increasing public interest in and scientific investigation into establishing dietary approaches that can be undertaken for the prevention and treatment of CVD. This Special Issue provides an insight into the influential role of nutrition and dietary habits on cardiovascular health and disease, as well as their mechanisms of therapeutic and preventive action.
Research & information: general --- Biology, life sciences --- Food & society --- magnesium deficiency --- arterial hypertension --- vascular tone --- arterial stiffness --- vascular remodeling --- insulin resistance --- magnesium supplementation --- dietary magnesium intake --- Zeb2 --- cardiac fibroblast --- activated myofibroblast --- cardiac fibrosis --- fibroblast contractility --- fish oil --- omega-3 fatty acids --- eicosapentaenoic acid (EPA) --- docosahexaenoic acid (DHA) --- cardiovascular disease --- irisin --- pediatric --- children --- nutrition --- diet --- body composition --- metabolic syndrome --- obesity, neonates --- Mediterranean diet --- inflammation --- nutrients --- polyphenols --- MUFA --- PUFA --- bioactive compounds --- phytosterols --- dietary pattern --- Aronia melanocarpa --- standardized extract --- dietary strategies --- supplementation --- cocaine --- cardiovascular health --- heart disease --- acute effects --- chronic effects --- marinobufagenin --- ouabain --- salt --- hypertension --- fibrosis --- Panax quinquefolius --- ginseng berry --- myocardial infarction --- phenolic compounds --- vascular aging --- vascular calcification --- arteriosclerosis --- Klotho --- chronic kidney disease (CKD), cancer --- diabetes --- heart failure --- micronutrients --- iron --- vitamins --- trace elements --- vitamin D --- seasonal variation --- lifestyle --- cytokines --- lipids --- mechanisms --- immunoregulatory --- eicosapentaenoic acid --- docosahexaenoic acid --- omega-3 polyunsaturated fatty acids --- coronary heart disease --- stretching --- TGF-β1 --- n/a
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There is unequivocal experimental, epidemiological, and clinical evidence demonstrating a correlation between diet and increased risk of cardiovascular disease (CVD). While nutritionally-poor diets can have a significant negative impact on cardiovascular health, dietary interventions with specific nutrients and/or functional foods are considered cost-effective and efficient components of prevention strategies. It has been estimated that nutritional factors may be responsible for approximately 40% of all CVD. Indeed, in one of the seminal studies conducted on modifiable risk factors and heart health (the INTERHEART study), >90% of all myocardial infarctions were attributed to preventable environmental factors with nutrition identified as one of the important determinants of CVD. There is an increasing public interest in and scientific investigation into establishing dietary approaches that can be undertaken for the prevention and treatment of CVD. This Special Issue provides an insight into the influential role of nutrition and dietary habits on cardiovascular health and disease, as well as their mechanisms of therapeutic and preventive action.
magnesium deficiency --- arterial hypertension --- vascular tone --- arterial stiffness --- vascular remodeling --- insulin resistance --- magnesium supplementation --- dietary magnesium intake --- Zeb2 --- cardiac fibroblast --- activated myofibroblast --- cardiac fibrosis --- fibroblast contractility --- fish oil --- omega-3 fatty acids --- eicosapentaenoic acid (EPA) --- docosahexaenoic acid (DHA) --- cardiovascular disease --- irisin --- pediatric --- children --- nutrition --- diet --- body composition --- metabolic syndrome --- obesity, neonates --- Mediterranean diet --- inflammation --- nutrients --- polyphenols --- MUFA --- PUFA --- bioactive compounds --- phytosterols --- dietary pattern --- Aronia melanocarpa --- standardized extract --- dietary strategies --- supplementation --- cocaine --- cardiovascular health --- heart disease --- acute effects --- chronic effects --- marinobufagenin --- ouabain --- salt --- hypertension --- fibrosis --- Panax quinquefolius --- ginseng berry --- myocardial infarction --- phenolic compounds --- vascular aging --- vascular calcification --- arteriosclerosis --- Klotho --- chronic kidney disease (CKD), cancer --- diabetes --- heart failure --- micronutrients --- iron --- vitamins --- trace elements --- vitamin D --- seasonal variation --- lifestyle --- cytokines --- lipids --- mechanisms --- immunoregulatory --- eicosapentaenoic acid --- docosahexaenoic acid --- omega-3 polyunsaturated fatty acids --- coronary heart disease --- stretching --- TGF-β1 --- n/a
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