Immature carob pods extract and its fractions prevent lipid metabolism disorders and lipoprotein-rich plasma oxidation in mice: A phytochemical and pharmacological study.

ETHNOPHARMACOLOGICAL RELEVANCE: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases. AIMS: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight. RESULTS: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks' experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner. CONCLUSION: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance.

Polyphenol-rich extract from loquat fruit peel prevents hyperlipidemia and hepato-nephrotoxicity in mice: in vivo study and in silico prediction of possible mechanisms involving identified polyphenols and/or their circulating metabolites.

Hyperlipidemia is the most well-known cause of metabolic complications and tissue toxicity such as liver steatosis, atherosclerosis and obesity. This study aims to evaluate the preventive effect of loquat fruit peel extract (PE) against tyloxapol-induced hyperlipidemia and related tissue lipotoxicity in mice. The in vivo study was conducted on mice injected daily with tyloxapol at 100 mg per kg B.W. and treated simultaneously with the PE at concentrations of 100 and 200 mg kg-1 or fenofibrate for 28 days. Plasma and tissue lipid biochemical analyses were undertaken using enzymatic methods. The antioxidative stress was revealed by measuring the malondialdehyde content and activities of superoxide dismutase and catalase as well as the scavenging activity against lipoperoxyl radicals. The PE significantly prevented oxidative stress and restored lipid metabolism, plasma glucose, body weight, organ relative mass and biomarkers of hepato-nephrotoxicity as well as the histological structure of the liver and kidneys. It contains five major polyphenols, namely, ferulic acid, caffeic acid, neochlorogenic acid, chlorogenic acid and quercetin. According to molecular docking analysis, these compounds and their circulating metabolites could interact with major proteins implicated in lipid metabolism and oxidative stress. Overall, the study suggests that PE could prevent hyperlipidemia and related toxic tissue complications.

Loquat fruit peel extract regulates lipid metabolism and liver oxidative stress in mice: In vivo and in silico approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: In Moroccan traditional medicine, fresh or dried loquat (Eriobotrya japonica (Thunb.) Lindl.) fruit peels infused in water and taken for 45 days are used as natural remedies against hypercholesterolemia, hyperglycemia and cardiovascular diseases. This is the first experimental study approving the folk medicinal use of loquat fruit peels originated from eastern Morocco. AIM OF THE STUDY: The study aims to investigate the effect of loquat fruit peel extract on lipid metabolism and liver oxidative status in mice as well as to predict the possible mechanisms. MATERIALS AND METHODS: The study was carried out using high fat/fructose diet-induced hyperlipidemic mice model treated with the loquat peel extract for 45 days at two doses (100 and 200 mg/kg/day) in comparison to fenofibrate drug. The plasma, tissue, fecal and biliary lipids and blood glucose were analyzed using enzymatic methods. The liver oxidative status was evaluated and the polyphenol profiling was conducted using the HPLC-DAD method. Possible mechanisms involved in the observed pharmacological effects were predicted by in silico method. RESULTS: The extract at a dose of 200 mg/kg possessed higher effect than at 100 mg/kg. It significantly reduced plasma total cholesterol (TC), triglycerides (TG), LDL-cholesterol, atherogenic index, LDL-C/HDL-C ratio and plasma glucose (-36%, -45%, -45%, -82%, -87%, 58%, respectively), while the HDL-cholesterol was increased (+172%). Moreover, the extract reduced TC and TG in the liver and adipose tissue by increasing their excretion in bile and fecal matter. It prevented the liver oxidative stress and decreased body weight and organ relative mass. The extract appears to be nontoxic (LD50 > 5000 mg/kg) and contains five polyphenols including ferulic acid (32.74 ± 0.71 mg/g), caffeic acid (21.48 ± 0.32 mg/g), 5-O-Caffeoylquinic acid (112.15 ± 1.86 mg/g), chlorogenic acid (42.05 ± 0.92 mg/g) and quercetin (32.69 ± 0.68 mg/g). These phenolics and/or their circulating metabolites presented differential interaction capacities with the potential enzymes and transcription factors implicated in lipid homeostasis such as HMG-CoA reductase, lipoprotein lipase, fatty acid synthase, Cyp7a1, ABCG, PPARs, RXR, FXR and RAR. CONCLUSION: Our findings justify the traditional use of loquat fruit peels and suggest that their aqueous extract could be used as substrate to produce phytotherapeutic drugs or dietary supplements to prevent hyperlipidemia, hyperglycemia and related cardiovascular diseases.

Flavan-3-ols and Cardiometabolic Health: First Ever Dietary Bioactive Guideline.

Guideline recommendation for a plant bioactive such as flavan-3-ols is a departure from previous recommendations because it is not based on deficiencies but rather improvement in health outcomes. Nevertheless, there is a rapidly growing body of clinical data reflecting benefits of flavan-3-ol intake that outweigh potential harms. Thus, the objective of the Expert Panel was to develop an intake recommendation for flavan-3-ols and cardiometabolic outcomes to inform multiple stakeholders including clinicians, policymakers, public health entities, and consumers. Guideline development followed the process set forth by the Academy of Nutrition and Dietetics, which includes use of the Evidence to Decision Framework. Studies informing this guideline (157 randomized controlled trials and 15 cohort studies) were previously reviewed in a recently published systematic review and meta-analysis. Quality and strength-of-evidence along with risk-of-bias in reporting was reviewed. In drafting the guideline, data assessments and opinions by authoritative scientific bodies providing guidance on the safety of flavan-3-ols were considered. Moderate evidence supporting cardiometabolic protection resulting from flavan-3-ol intake in the range of 400-600 mg/d was supported in the literature. Further, increasing consumption of dietary flavan-3-ols can help improve blood pressure, cholesterol concentrations, and blood sugar. Strength of evidence was strongest for some biomarkers (i.e., systolic blood pressure, total cholesterol, HDL cholesterol, and insulin/glucose dynamics). It should be noted that this is a food-based guideline and not a recommendation for flavan-3-ol supplements. This guideline was based on beneficial effects observed across a range of disease biomarkers and endpoints. Although a comprehensive assessment of available data has been reviewed, evidence gaps identified herein can inform scientists in guiding future randomized clinical trials.

Brazilian passion fruit as a new healthy food: from its composition to health properties and mechanisms of action.

The Brazilian biodiversity is one of the largest in the world, with about 41 000 species cataloged within two global biodiversity hotspots: Atlantic Forest and Cerrado, the Brazilian savannah. Passiflora, known also as passion flowers, is a genus of which 96% of its species are distributed in the Americas, mainly Brazil and Colombia. Passion fruit extracts have a commercial value on a global scale through the pharmaceutical, nutraceutical, self-care, and food and beverage industries. Passiflora are widely studied due to their potential antioxidant, anti-inflammatory, anxiolytic, antidepressant and vascular and neuronal protective effects, probably owing to their content of polyphenols. Passiflora setacea DC is a species of wild passion fruit from the Brazilian Cerrado, rich in flavonoid C-glycosides, homoorientin, vitexin, isovitexin and orientin. Intake of these plant food bioactives has been associated with protection against chronic non-communicable diseases (CNDCs), including cardiovascular diseases, cancers, and neurodegenerative diseases. In this review, we aimed to discuss the varieties of Passiflora, their content in plant food bioactives and their potential molecular mechanisms of action in preventing or reversing CNDCs.

Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design.

In a series of our previous works, we revealed the beneficial effects of applied soy isoflavones (genistein or daidzein) on the wide context of corticosteroidogenesis in vivo, in a rat model of the andropause. Soy isoflavones decreased the circulating levels of pituitary adrenocorticotropic hormone, inhibited aldosterone secretion, as well as corticosterone production and secretion, but stimulated dehydroepiandrosterone secretion, all in andropausal rats. In vitro studies indicate that the mechanism underlying these hormonal changes relies on inhibition of the pituitary tyrosine kinase and adrenocortical 3ß-hydroxysteroid dehydrogenase enzymes by soy isoflavones. Although the clinical studies are in their infancy, the opinion is that genistein and daidzein have therapeutic potential for the safe treatment of ageing-caused androgen deprivation and glucocorticoid excess with related metabolic/hemodynamic issues in males. Our accumulated experience and knowledge in the field of biomedical effects of plant polyphenols have provided a platform for potential recommending the agenda to organize and accelerate experimental research aimed at producing the optimal supplementation. We hypothesize that an in vivo approach should first be exploited in the sequence of investigative steps, followed by in vitro studies and synchronously conducted molecular docking analyses. In vivo research, besides establishing the margin of exposure safety or adjustment of the correct polyphenol dose, enables identification and quantification of the metabolites of applied polyphenols in the blood. Subsequent in vitro exploitation of the metabolites and related docking analyses provide clarification of the molecular mechanisms of action of applied polyphenols. Chemical modification of the polyphenol structure or coupling it with nanoparticles might be the next step in optimizing the design of supplementation. Selected, intact or chemically-modified polyphenol molecules should be included in preclinical studies on a more closely-related species, while clinical studies would finally assess the safety and effectiveness of a polyphenol-based remedial strategy. The final supplement represents a product of an appropriate technological process, conducted in accordance with the recommendations derived from the preceding research.

Citrus Flavanones Upregulate Thyrotroph Sirt1 and Differently Affect Thyroid Nrf2 Expressions in Old-Aged Wistar Rats.

A growing population of elderly people consume citrus flavanones, naringenin, and hesperetin in the form of fruits or juices. Flavanones are bioactives with potent antioxidant properties and have potential in slowing down the aging process. Because flavanones exert controversial effects on pituitary-thyroid functioning, our study on the old-aged rat model aimed to elucidate the mechanism by which naringenin and hesperetin affect this axis. Naringenin and hesperetin increased the Sirt1 mRNA level by 91 and 71% (p < 0.05), which was followed by increased Sirt1 expression by 20 and 15% (p < 0.05), respectively. Only naringenin decreased thyroid-stimulating hormone expression by 20% (p < 0.05). Thyroid peroxidase protein expression was upregulated after naringenin or hesperetin by 62 and 43% (p < 0.05), respectively. Naringenin lowered mRNA levels of Tpo, Sod1, Sod2, Cat, and Nrf2 by 50, 32, 45, 35, and 42% (p < 0.05), respectively, and increased Gpx by 54% (p < 0.05), while hesperetin decreased Sod1 and Sod2 mRNA levels by 46 and 55% (p < 0.05), respectively. Naringenin increased the protein expressions of Nrf2 and SOD2 by 58 and 50% (p < 0.05), respectively, and decreased SOD1 expression by 48% (p < 0.05), while hesperetin protein decreased expressions of SOD1 and Nrf2 by 63 and 32% (p < 0.05), respectively. Altogether, our findings suggest that citrus flavanones contribute to restoring the impaired thyroid functioning in the old-aged rats.

Acute Effects of the Consumption of Passiflora setacea Juice on Metabolic Risk Factors and Gene Expression Profile in Humans.

BACKGROUND: Passiflora setacea (PS) is a passionfruit variety of the Brazilian savannah and is a rich source of plant food bioactives with potential anti-inflammatory activity. This study aimed to investigate the effect of an acute intake of PS juice upon inflammation, metabolic parameters, and gene expression on circulating immune cells in humans. METHODS: Overweight male volunteers (n = 12) were enrolled in two double-blind placebo-controlled studies. Blood samples were collected from fasting volunteers 3 h after the consumption of 250 mL of PS juice or placebo (PB). Metabolic parameters (insulin, glucose, total cholesterol, high-density lipoprotein (LDL), high-density lipoprotein (HDL), and total triglycerides) and circulating cytokines were evaluated (study 1). Peripheral blood mononuclear cell (PBMC) from the same subjects were isolated and RNA was extracted for transcriptomic analyses using microarrays (study 2). RESULTS: Insulin and homeostatic model assessment for insulin resistance (HOMA-IR) levels decreased statistically after the PS juice intake, whereas HDL level increased significantly. Interleukin (IL)-17A level increased after placebo consumption, whereas its level remained unchanged after PS juice consumption. Nutrigenomic analyses revealed 1327 differentially expressed genes after PS consumption, with modulated genes involved in processes such as inflammation, cell adhesion, or cytokine-cytokine receptor. CONCLUSION: Taken together, these clinical results support the hypothesis that PS consumption may help the prevention of cardiometabolic diseases.

Circulating Anthocyanin Metabolites Mediate Vascular Benefits of Blueberries: Insights From Randomized Controlled Trials, Metabolomics, and Nutrigenomics.

Potential health benefits of blueberries may be due to vascular effects of anthocyanins that predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation. The effects were similar to those of wild blueberries containing similar amounts of anthocyanins, whereas control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month wild blueberry consumption increased flow-mediated dilation and lowered 24-hour ambulatory systolic blood pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 21 correlated with acute and chronic flow-mediated dilation improvements, respectively. Injection of these metabolites improved flow-mediated dilation in mice. Daily wild blueberry consumption led to differential expression (>1.2-fold) of 608 genes and 3 microRNAs, with Mir-181c showing a 13-fold increase in peripheral blood mononuclear cells. Patterns of 13 metabolites were independent predictors of gene expression changes and pathway enrichment analysis revealed significantly modulated biological processes involved in cell adhesion, migration, immune response, and cell differentiation. Our results identify anthocyanin metabolites as major mediators of vascular bioactivities of blueberries and changes of cellular gene programs. Trial registration: NCT025208.

Chronic consumption of a western diet modifies the DNA methylation profile in the frontal cortex of mice.

In our previous work in mice, we have shown that chronic consumption of a Western diet (WD; 42% kcal fat, 0.2% total cholesterol and 34% sucrose) is correlated with impaired cognitive function. Cognitive decline has also been associated with alterations in DNA methylation. Additionally, although there have been many studies analyzing the effect of maternal consumption of a WD on DNA methylation in the offspring, few studies have analyzed how an individual's consumption of a WD can impact his/her DNA methylation. Since the frontal cortex is involved in the regulation of cognitive function and is often affected in cases of cognitive decline, this study aimed to examine how chronic consumption of a WD affects DNA methylation in the frontal cortex of mice. Eight-week-old male mice were fed either a control diet (CD) or a WD for 12 weeks, after which time alterations in DNA methylation were analyzed. Assessment of global DNA methylation in the frontal cortex using dot blot analysis revealed that there was a decrease in global DNA methylation in the WD-fed mice compared with the CD-fed mice. Bioinformatic analysis identified several networks and pathways containing genes displaying differential methylation, particularly those involved in metabolism, cell adhesion and cytoskeleton integrity, inflammation and neurological function. In conclusion, the results from this study suggest that consumption of a WD alters DNA methylation in the frontal cortex of mice and could provide one of the mechanisms by which consumption of a WD impairs cognitive function.

Impact of Flavonols on Cardiometabolic Biomarkers: A Meta-Analysis of Randomized Controlled Human Trials to Explore the Role of Inter-Individual Variability.

Several  epidemiological  studies  have  linked  flavonols  with  decreased  risk  of  cardiovascular  disease  (CVD).  However,  some  heterogeneity  in  the  individual  physiological  responses to the consumption of these compounds has been identified. This meta-analysis aimed to  study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood  pressure and plasma glucose, as well as factors affecting their inter-individual variability. Data from  18 human randomized controlled trials were pooled and the effect was estimated using fixed or  random effects meta-analysis model and reported as difference in means (DM). Variability in the  response of blood lipids to supplementation with flavonols was assessed by stratifying various  population subgroups: age, sex, country, and health status. Results showed significant reductions  in total cholesterol (DM = -0.10 mmol/L; 95% CI: -0.20, -0.01), LDL cholesterol (DM = -0.14 mmol/L;  Nutrients 2017, 9, 117  2 of 21  95% CI: -0.21, 0.07), and triacylglycerol (DM = -0.10 mmol/L; 95% CI: -0.18, 0.03), and a significant  increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also  observed in fasting plasma glucose (DM = -0.18 mmol/L; 95%CI: -0.29, -0.08), and in blood pressure  (SBP: DM = -4.84 mmHg; 95% CI: -5.64, -4.04; DBP: DM = -3.32 mmHg; 95% CI: -4.09, -2.55).  Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian  countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and  normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk,  however, country of origin and health status may influence the effect of flavonol intake on blood  lipid levels.

Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats.

This study aimed to investigate effects of citrus flavanones naringenin (NAR) and hesperetin (HES) on liver antioxidant status and membrane phospholipid composition in 24-month-old rats. NAR and HES (15mg/kg) were administrated orally to male Wistar rats, once per day, for 4weeks. Control group received either vehicle (sunflower oil) or remained intact. The results showed decreased (p<0.05) activity of antioxidant enzymes (AOE), specifically catalase (CAT), superoxide dismutase (SOD) 1 and glutathione reductase (GR) in the liver of intact control old-aged rats in comparison to young intact controls. Flavanone administration to old-aged males increased (p<0.05) examined AOE activities in comparison to vehicle-administered animals. Namely, NAR was more potent in comparison to HES regarding the increase (p<0.05) in activities of examined antioxidant enzymes (SOD 1 and 2, glutathione peroxidase-GPx and GR) and the liver glutathione (GSH), while HES elevated (p<0.05) only activity of CAT and GR. Both flavanones significantly decreased (p<0.05) TBARS and improved (p<0.05) membrane phospholipid composition in favor of n-3 PUFA and n-6/n-3 PUFA ratio. Both flavanones did not affect liver histology and reduced (p<0.05) alanine aminotransferase and aspartate aminotransferase levels in serum. The results of this study indicate beneficial potential of citrus flavanones in the old-aged rat liver.

Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state.

BACKGROUND: In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-α-stimulated endothelial cells. Nuclear factor kappa B (NF-κB) reporter gene assays confirmed that MOF decrease the activity of NF-κB. Strong inter-individual variability in the leukocytes' DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. CONCLUSION: Our study revealed that an 8 week daily supplementation with 200 mg MOF modulates the expression of genes associated with cardiovascular disease pathways without major changes of their DNA methylation state. However, strong inter-individual variation in leukocyte DNA methylation may obscure the subtle epigenetic response to dietary flavanols. Despite the lack of significant changes in DNA methylation, the modulation of gene expression appears to contribute to the observed vascular health effect of MOF in humans.

Dietary curcumin inhibits atherosclerosis by affecting the expression of genes involved in leukocyte adhesion and transendothelial migration.

SCOPE: The aim of the study was to examine the atheroprotective effect of dietary curcumin in a mouse model of atherosclerosis and to identify its cellular and molecular targets at the vascular level. METHODS AND RESULTS: ApoE(-/-) mice were fed with curcumin at 0.2% (wt/wt) in diet for 4 months. This supplementation reduced the extent of atherosclerotic lesion by 26% and induced changes in expression of genes implicated in cell adhesion and transendothelial migration or cytoskeleton organization, as revealed by a transcriptomic analysis in the aorta. Expression profile of these genes suggests reduction in both leukocyte adhesion and transendothelial migration. In agreement with this hypothesis, we observed a reduction (-37%) in macrophage infiltration in the plaque, as measured by immunohistochemistry, and, in vitro, a lower adhesion of monocytes to TNF-α-stimulated endothelial cells (-32%) after exposure to a nutritionally achievable concentration of curcumin. These changes in gene expression could be related to the observed increased expression of IκB protein and decrease of TNF-α-induced NF-κB/DNA binding and NF-κB-transcriptional activity upon exposure to curcumin. CONCLUSION: Our findings pointed out that the antiatherogenic effect of curcumin could be linked to its effect on gene networks and cell functions related to leukocyte adhesion and transendothelial migration via NF-κB-dependent pathways.

Citrus flavanones: what is their role in cardiovascular protection?

Flavanones, including hesperidin and naringin, are polyphenolic compounds highly and almost exclusively present in citrus. Epidemiological studies reported an inverse relationship between their intake and the risk of cardiovascular diseases. Clinical and experimental data further showed their antihypertensive, lipid-lowering, insulin-sensitizing, antioxidative, and anti-inflammatory properties, which could explain their antiatherogenic action in animal models. Although flavanones may be promising compounds that are particularly active in cardiovascular disease prevention, clinical data are still scarce and most in vitro data have been obtained under nonphysiologically relevant conditions. Moreover, the mechanisms responsible for flavanone action are not fully elucidated. Therefore, further research is needed to better evaluate and understand the protective effects of flavanones in cardiovascular diseases.

Atheroprotective effects of bilberry extracts in apo E-deficient mice.

Previous studies have demonstrated that the intake of berry foods was associated with a reduced risk of cardiovascular diseases. The aim of the present study was to evaluate the effects of two bilberry extracts, one rich in anthocyanins extracted from untreated bilberries (BE) and a second one extracted from yeast-fermented bilberries (FBE), on the development of atherosclerosis in apolipoprotein E-deficient mice (apo E(-/-)). Apo E(-/-) mice received for 16 weeks a diet supplemented with 0.02% of either BE or FBE. Atherosclerotic plaque area was measured in the aortic sinus. Supplementation of the diet with both bilberry extracts led to a significant inhibition of plaque development, whereas no effect on oxidative stress parameters or lipid profiles could be observed, suggesting the implication of other mechanisms of action. In addition, a better protection was observed with FBE, suggesting that the fermentation generates new bioactive compounds more effective in attenuating progression of the atherosclerotic lesions.

Catechin reduces atherosclerotic lesion development in apo E-deficient mice: a transcriptomic study.

Much experimental evidence supports a protective role of dietary flavonoids against cardiovascular diseases. The aim of the present study was to investigate the anti-atherosclerotic effects of catechin supplemented in the diet of apoE deficient mice at a low nutritional level and to explore the mechanisms of action by a transcriptomic approach. After 6 weeks of supplementation, atherosclerotic lesions were assessed by histomorphometry and several markers of lipid, inflammation and oxidative stress status were evaluated. Analysis of the global gene expression in the aorta was carried out using pangenomic arrays. Catechin supplementation reduced the mean atherosclerotic lesion area by 32% but had no effect on total cholesterol and triacylglycerol levels in the plasma and the liver. The plasma antioxidant capacity (FRAP) and inflammatory status (serum amyloid A) were unchanged. The expression of 450 genes was significantly modified by catechin supplementation. Some of the most significantly down-regulated genes included genes coding for adhesion molecules such as CD34 and PSGL-1 known to play a key role in leukocyte adhesion to the endothelium. Other genes involved in energy metabolism, lipid metabolism and lipids trafficking such as FABP4, LPL and SCARA5 were down-regulated and may contribute to the atheroprotective effect of catechin. This work shows that transcriptomic allows characterizing the biological effects of low doses of flavonoids where common markers were not significantly affected.

Apple polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient mice.

Atherosclerosis, which is closely linked to nutritional habits, is a major cause of mortality in Western countries. Most of the previous investigations carried out on health effects of apples have been focused on their capacity to lower lipid concentration as well as on their antioxidant effects. The aim of the present study was to investigate the antiatherosclerotic effects of apple polyphenols and fibers. A crude apple polyphenol extract and low-viscosity apple fibers isolated from cider apples were administered separately or in association with the diet of apo E-deficient mice. After 4 months of supplementation, lipemia and oxidative stress biomarkers were measured and atheroslerotic lesions assessed by histomorphometry. Total plasmatic cholesterol and triacylgycerol levels were not affected by supplementation, and hepatic cholesterol level was lower in the group supplemented with both fibers and polyphenols. Uric acid concentrations and antioxidant capacity (FRAP) in plasma were reduced in all groups supplemented with polyphenols or fibers. The mean lesion area was reduced by 17, 38, and 38%, respectively, for the polyphenol, fiber, and polyphenol + fiber groups. Apple constituents supplied at nutritional doses therefore limit the development of atherosclerotic lesions in the aorta of apo E-deficient mice. On the basis of the results, we hypothesize that apple fibers and polyphenols may play a role in preventing atherosclerosis disease by decreasing uric acid plasma level.