Wild blueberry (V. angustifolium) improves TNFα-induced cell barrier permeability through claudin-1 and oxidative stress modulation in Caco-2 cells.

Increasing evidence links the impairment of intestinal permeability (IP), a feature of the intestinal barrier, to numerous dysmetabolic and dysfunctional conditions. Several host and environmental factors, including dietary factors, can negatively and/or positively affect IP. In this regard, polyphenol-rich foods including berries have been proposed as potential IP modulators. However, the exact mechanisms involved are not yet fully elucidated. The aim of the present study was to evaluate the effect of a wild blueberry (WB; V. angustifolium) powder, naturally rich in polyphenols, to affect Caco-2 cell monolayer permeability and to identify the potential mechanisms in modulating the IP process. Caco-2 cells were incubated with TNF-α (10 ng mL-1), as a pro-inflammatory stimulus, and supplemented for 24 hours with different concentrations (1 and 5 mg mL-1) of WB powder. The integrity of the intestinal cell monolayer was evaluated by measuring the transepithelial electrical resistance (TEER) and the paracellular transport of FITC-dextran. In addition, the production of the tight junction proteins, such as claudin-1 and occludin, as well as protein carbonyl and 8-hydroxy 2 deoxyguanosine, as oxidative stress markers, were quantified in the supernatant by ELISA kits. Overall, the treatment with WB powder (5 mg mL-1) mitigated the loss of Caco-2 cell barrier integrity, as documented by an increase in TEER and a reduction in FITC values. This modulation was accompanied by an upregulation of claudin-1 and a reduction of 8-OHdG. Conversely, no effect was documented for the lower concentration (1 mg mL-1) and the other IP markers, as well as oxidative stress markers analysed. In conclusion, our findings suggest a potential role of WB in the modulation of cell barrier integrity. This modulation process could be attributed to an increase in claudin-1 expression and a reduction in 8-OHdG. Further studies should be performed to corroborate the results obtained. In addition, since the effects were observed at doses of WB achievable with the diet, these findings should be substantiated also through in vivo approaches.

Berry Dietary Interventions in Metabolic Syndrome: New Insights.

Metabolic Syndrome (MetS) is characterized by a group of dysmetabolic conditions, including abdominal obesity, dyslipidemia, glucose intolerance and/or insulin resistance, and hypertension. Generally, MetS is accompanied by an exacerbation of oxidative stress, inflammation, and vascular dysfunction. Increasing evidence suggests that berries and berry bioactives could play a potential role in the prevention and mitigation of the risk factors associated with MetS. The present systematic review summarizes the more recently available evidence deriving from human intervention studies investigating the effect of berries in subjects with at least three out of five MetS parameters. The PubMed, Scopus, and Embase databases were systematically searched from January 2010 until December 2022. A total of 17 human intervention trials met the inclusion criteria. Most of them were focused on blueberry (n = 6), cranberry (n = 3), and chokeberry (n = 3), while very few or none were available for the other berries. If considering MetS features, the main positive effects were related to lipid profile (low and high-density lipoproteins, cholesterol, and triglycerides) following blueberries and chokeberries, while conflicting results were documented for anthropometric parameters, blood pressure, and fasting blood glucose levels. Other markers analyzed within the studies included vascular function, oxidative stress, and inflammation. Here, the main positive effects were related to inflammation with a reduction in interleukin 6 and tumor necrosis factor-alpha following the intake of different berries. In conclusion, although limited, the evidence seems to support a potential role for berries in the modulation of lipid profile and inflammation in subjects with MetS. Furthermore, high-quality intervention trials are mandatory to demonstrate the role of berries in reducing risk factors for MetS and related conditions. In the future, such a demonstration could bring the adoption of berries as a potential dietary strategy to prevent/counteract MetS and related risk factors.

Blueberries and their bioactives in the modulation of oxidative stress, inflammation and cardio/vascular function markers: a systematic review of human intervention studies.

Blueberries represent a rich source of (poly)phenols and other bioactive compounds. Numerous in vitro and animal model studies documented the potential health-promoting properties of blueberries and blueberry-bioactives, while little is still known about their effects in humans. The objective of the present systematic review is to provide main evidence and the potential mechanisms of action of blueberry and its (poly)phenols in the regulation of markers related to oxidative stress, inflammation, vascular and cardiometabolic function in health and disease states. A total of 45 human intervention studies were included in this review. Overall, the evidence suggests that blueberries may play a role in the improvement of markers of vascular function. Their effects were observed following both post-prandial and long-term consumption, particularly in subjects with risk factors and/or disease conditions. Conversely, the conflicting results on inflammation, oxidative stress and cardiometabolic risk markers were most likely due to differences among studies in terms of study design, subject characteristics, duration of intervention, dosage, and type of biomarkers analyzed. For these reasons, high-quality, well-designed, human intervention studies are warranted to strengthen the current findings on vascular function and provide more evidence about the impact of blueberries on the different markers considered. In addition, studies focusing on the relationship between the structure and the function of (poly)phenols will be fundamental for a better comprehension of the mechanisms behind the health effects observed.

Vitamin D Counteracts Lipid Accumulation, Augments Free Fatty Acid-Induced ABCA1 and CPT-1A Expression While Reducing CD36 and C/EBPß Protein Levels in Monocyte-Derived Macrophages.

The biologically active form of vitamin D, calcitriol (VD3), has received great attention for its extraskeletal effects, such as a protective role on the cardiovascular system. The aim of the present work is to test the capacity of VD3 to affect lipid metabolism and fatty acid accumulation in an in vitro model of monocyte (THP-1)-derived macrophages. Cells were treated for 24 h with oleic/palmitic acid (500 µM, 2:1 ratio) and different VD3 concentrations (0.1, 1, 10, 50 and 100 nM). Lipid accumulation was quantified spectrophotometrically (excitation: 544 nm, emission: 590 nm). C/EBPß, PPAR-γ1, CD36, CPT-1A, and ABCA1 protein levels were assessed by ELISA kits at different time-points (1, 2, 4, 8, and 24 h). VD3 at 50 and 100 nM significantly reduced fatty acids accumulation in macrophages by 27% and 32%, respectively. In addition, tested at 50 nM, VD3 decreased CD36, PPAR-γ1, and C/EBPß, while it increased ABCA1 and CPT-1A protein levels in free fatty acid-exposed cells. In conclusion, VD3 reduced fatty acid accumulation in THP-1-derived macrophages exposed to lipid excess. The anti-atherogenic effect of VD3 could be ascribable to the regulation of proteins involved in lipid transport and clearance.

A mix of chlorogenic and caffeic acid reduces C/EBPß and PPAR-γ1 levels and counteracts lipid accumulation in macrophages.

PURPOSE: Chlorogenic acid (CGA) and caffeic acid (CA) are bioactive compounds in whole grains, berries, apples, some citrus fruits and coffee, which are hypothesized to promote health-beneficial effects on the cardiovascular system. This study aimed to evaluate the capacity of CGA and CA to reduce lipid accumulation in macrophages, recognized as a critical stage in the progression of atherosclerosis. Furtherly, the modulation of CCAAT/enhancer-binding protein ß (C/EBPß) and peroxisome proliferator-activated receptor- γ1 (PPAR-γ1), as transcription factors involved in lipid metabolism, was evaluated. METHODS: THP-1-derived macrophages were treated for 24 h with 0.03, 0.3, 3 and 30 µM of CGA and CA, tested alone or in combination, and a solution of oleic/palmitic acid (500 µM, 2:1 ratio). Lipid storage was assessed spectrophotometrically through fluorescent staining of cells with Nile red. C/EBPß and PPAR-γ1 mRNA and protein levels were evaluated by RT-PCR and enzyme-linked immunosorbent assay, respectively. RESULTS: The mix of CGA + CA (1:1 ratio) reduced lipid accumulation at all concentrations tested, except for the highest one. The greatest effect ( - 65%; p < 0.01) was observed at the concentration of 0.3 µM for each compound. The same concentration significantly (p < 0.01) downregulated C/EBPß and PPAR-γ1 gene expression and reduced their protein levels at 2 h and 24 h, respectively. CONCLUSION: The results indicate that the capacity of CGA + CA mix to reduce lipid storage in macrophages is mediated by a reduction in the expression of transcription factors C/EBPß and PPAR-γ1.

An Overview of Registered Clinical Trials on Glucosinolates and Human Health: The Current Situation.

Epidemiological studies suggest a potential role of glucosinolates (GSLs) and isothiocyanates on human health. However, evidence from intervention studies, due to heterogeneity in features of study design, duration, participants, food or food components administered, and outcomes analyzed, is still insufficient. The current review aims to provide an overview of the trials on GSLs and GSL-rich foods registered over the last 20 years with the intention to summarize the main topics and results, but also the existing gaps that still need to be covered. Studies were collected by using ClinicalTrials.gov and the International Standard Randomized Controlled Trial Number (ISRCTN) registry. A total of 87 registered trials were identified with which most of them were performed by using extracts or pure compounds (n = 60) while few were conducted with GSL-rich foods (n = 27). In detail, sulforaphane was the most investigated compound, while broccoli was the most frequent food tested in the trials. The majority of the studies assessed the health effects of GSLs focusing on outcomes related to cancer and cognitive function, even if the current findings are not univocal. Emerging topics also included the study of GSLs and gut microbiota interaction and impact on skin health. Further attention was also drawn to the bioavailability of GSLs and/or derivatives from foods, extracts, and single compounds by also considering the contribution of the different genetic polymorphisms. In conclusion, although considerable efforts have been made to study GSLs and GSL-rich foods, further studies are necessary to provide evidence-based research and to corroborate the findings obtained. The interindividual response due to genetic polymorphisms should be further investigated in order to explore the contribution to the overall beneficial effect.