Uraemic toxin-induced inflammation and oxidative stress in human endothelial cells: protective effect of polyphenol-rich extract from açaí.

NEW FINDINGS: What is the central question of this study? Does a polyphenol-rich extract from açaí have a potential role in preventing uraemic toxin-induced endothelial cell dysfunction? What is the main finding and its importance? Polyphenols from açaí prevented cell death, restored migratory capacity, protected from inflammation and contributed to the restoration of the antioxidant response in endothelial cells exposed to uraemic toxins. The protective role of açaí against toxic effects exerted by uraemic toxins presents a potential new therapeutic target in endothelial cells. ABSTRACT: In chronic kidney disease (CKD), progressive loss of kidney function results in the accumulation of protein-bound uraemic toxins such as p-cresyl sulfate (pCS) and indoxyl sulfate (IS). Among strategies to ameliorate the harmful actions of uraemic toxins, phenolic compounds have been extensively studied. The main goal of this work was to evaluate the antioxidant and anti-inflammatory actions of phenolic-rich açaí seed extract (ASE) in response to endothelial dysfunction induced by IS and pCS, in human umbilical vein endothelial cells (HUVECs). Cells were treated with ASE (10 µg ml-1 ) in the presence or absence of IS (61 µg ml-1 ) and pCS (40 µg ml-1 ). Cell viability, cell death, cell migratory capacity and inflammatory biomarker expression were evaluated. Cellular antioxidant response was measured through the activity and expression of antioxidant enzymes, and oxidative damage was evaluated. IS and pCS lowered cell viability, triggered cell death and lowered the migratory capacity in endothelial cells (P < 0.05). ASE prevented cell death and restored the migratory capacity in cells exposed to IS. Both toxins up-regulated pro-inflammatory cytokine expression, and ASE was able to beneficially counteract this effect. Tumour necrosis factor-α secretion was greater in uraemic toxin-treated cells and ASE reversed this phenomenon in cells treated with both toxins concomitantly (P < 0.05). With regard to the antioxidant response, superoxide dismutase expression was strikingly lower in cells treated with both toxins, and ASE inhibited this harmful effect (P < 0.05). From the results, we conclude that ASE exerted protective effects on inflammation and oxidative stress caused by uraemic toxins (particularly by IS) in human endothelial cells.

Polyphenol-rich açaí seed extract exhibits reno-protective and anti-fibrotic activities in renal tubular cells and mice with kidney failure.

The main goal of this study was to evaluate the reno-protective effects of a phenolic-rich Açaí seed extract (ASE) in mice with kidney failure. Kidney failure was induced chemically with an adenine-rich diet (0.25% w/w for 4 weeks) in male CD1 Swiss mice. Mice were then provided daily with ASE (at a dose of ~ 350 mg/kg/day) in drinking water for 4 weeks. Adenine mice exhibited renal dysfunction evidenced by increased proteinuria, increased uremia, extensive tubular atrophy and kidney fibrosis associated with overexpression of pro-fibrotic genes (collagen 1a1, transforming growth factor ß1, TGF-ß1) and markers of tubular injury (such as Kidney injury molecule-1, KIM-1). ASE was able to beneficially counteract all these effects. ASE improved oxidative damage and fibrosis by decreasing carbonylated protein and MDA concentrations, as well as collagen deposition in renal tissue. ASE decreased the expression of TGF-ß1 gene and the abundance of protein TGF-ß1 in kidneys. It further decreased both expression and urinary excretion of tubular injury biomarkers, e.g., KIM-1 and Neutrophil gelatinase-associated lipocalin. CKD ASE-treated mice exhibited higher polyphenol content and total antioxidant capacity compared to control mice. ASE further prevented the expression of profibrotic genes in HK2 human tubular cells exposed to uremic toxins. Taken together, these findings suggest that ASE exerted potent reno-protective and anti-fibrotic effects through its antioxidant activity and the modulation of the TGF-ß1 pathway.

Green banana flour supplementation improves obesity-associated systemic inflammation and regulates gut microbiota profile in mice fed high-fat diets.

This study evaluated the effect of green banana flour (GBF) consumption on obesity-related conditions in mice fed high-fat diets. GBF was prepared using stage 1 green banana pulp, which was dehydrated and milled. Mice were fed a control diet (n = 20; 10% of energy from lipids) or a high-fat diet (n = 20; 50% of energy from lipids). After 10 weeks, mice were divided into 4 groups based on feed: standard chow (SC; n = 10), standard with 15% GBF (SB; n = 10), high-fat diet (HF; n = 10) and high-fat diet with 15% GBF (HFB; n = 10) for 4 weeks. HFB exhibited lower gains in body weight (-21%; p < 0.01) and in all fat pads (p < 0.01) compared with the HF group. SC, SB, and HFB showed smaller retroperitoneal white adipose tissue diameters (p < 0.001). SB and HFB-treated mice showed lower levels of leptin, IL-6, and TNF-α compared with the SC and HF groups (p < 0.01). In the GBF-fed groups, there was a reduction in the abundance of Firmicutes (SB: -22%; HFB: -23%) and an increase in Bacteroidetes (SB: +25%; HFB: +29%) compared with their counterparts. We demonstrated that GBF consumption attenuated inflammation and improved metabolic status, adipose tissue remodeling, and the gut microbiota profile of obese mice. Novelty: Green banana flour (GBF) consumption, rich in resistant starch, regulates body weight in mice fed high-fat diets. GBF consumption improves fat pad distribution in mice fed high-fat diets. GBF improves obesity-associated systemic inflammation and regulates gut microbiota profile in mice fed high-fat diets.

Resistant starch from green banana (Musa sp.) attenuates non-alcoholic fat liver accumulation and increases short-chain fatty acids production in high-fat diet-induced obesity in mice.

This study aimed to investigate the effect of resistant starch from green banana (GB) on steatosis and short-chain fatty acid (SCFAs) production in high fat diet-induced obesity in mice. High-fat green banana group (HFB) exhibited lower gains in BM (body mass; -6%; P < 0.01) compared with High-fat diet group (HF). Additionally, HFB mice showed reduction in liver steatosis (-28%, P < 0.01) with reduction of 93% in hepatic triacylglycerol (P < 0.01) compared to HF-diet-fed mice. In addition, the protein abundance of AMPKp/AMPK, HMGCoA-r and FAS were downregulated in livers of HFB mice (P < 0.01), relatively to the HF-diet-fed mice. ABCG8 and ABCG5 were up-regulated in HFB group compared to HF group (P < 0.01). Furthermore, the HFB fed-mice produced the highest amount of SCFAs (p < 0.05) compared to its counterpart HFD. In conclusion, we demonstrated that resistant starch from GB improved metabolic parameters by modulating the expression of key proteins involved in liver lipid metabolism.

Antiadipogenic effects of açai seed extract on high fat diet-fed mice and 3T3-L1 adipocytes: A potential mechanism of action.

Body adiposity is an important risk factor for the development of chronic non-transmissible diseases. Studies on the process of adipogenesis have been extensively performed in vivo and in vitro models to describe the molecular and cellular bases of adipose tissue development and the effect of natural products in this process. The açai seed extract (ASE) has been evidenced as a potential regulator of body mass. In our work high-fat diet-fed mice treated with ASE (300 mg/Kg/d) (HFD-ASE) showed a lower adipose index (-32.63%, p < 0.001) than the high-fat diet-fed mice group (HFD) and the adipocytes from the HFD group were considerably enlarged (p < 0.001) compared to those in the control group (CG) and HFD-ASE group (+175% and +123%, respectively). We also evaluated the effects of ASE on the modulation of adipogenesis in 3T3-L1 cells. ASE exposure (25 and 100 µg/mL) led to a decrease of 26.6 (p < 0.05) in proliferation and also inhibited pre-adipocyte differentiation through the decreasing expression (p < 0.05) of transcription factors and adipogenic proteins such as PPARÉ£, SREBP-1, and FAS. These results show that the ASE reduce adipogenesis and suppress lipid accumulation in the in vivo model and in 3T3-L1 adipocytes and reinforce ASE as a potential strategy to modulate adipogenesis.

Determination of the binding properties of p-cresyl glucuronide to human serum albumin.

p-Cresyl glucuronide (p-CG) is a by-product of tyrosine metabolism that accumulates in patients with end-stage renal disease. p-CG binding to human serum albumin in physiological conditions (37 °C, pH 7.40) was studied by ultrafiltration (MWCO 10 kDa) and data were analyzed assuming one binding site. The estimated value of the association constant was 2.77 × 103 M-1 and a maximal stoichiometry of 3.80 mol per mole. At a concentration relevant for end-stage renal patients, p-CG was 23% bound to albumin. Competition experiments, using fluorescent probes, demonstrated that p-CG did not bind to Sudlow's site I or site II. The p-CG did not interfere with the binding of p-cresyl-sulfate or indoxyl sulfate to serum albumin.

Taioba (Xanthosoma sagittifolium) leaves: nutrient composition and physiological effects on healthy rats.

Several studies have shown that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases, diabetes, and cancer, mainly due to the presence of dietary fiber (DF) and polyphenols. Taioba (Xanthosoma sagittifolium) is an edible aroid widely grown in many parts of Africa, America, and Asia. The tubers portions of taioba are widely consumed; however, the leafy portions are generally discarded, despite their high nutritive value. In this study, we have partly characterized the DF of lyophiized taioba leaf (LTL), and assessed the possible protective effects on biochemical parameters and on bile acid (BA) production in colon and cecum, when fed to healthy rats for 4 wk. Forty-five Wistar rats were assigned to either of 5 groups: group 1 received AIN 93G diet (CG: Control); group 2 received AIN 93G containing 2.5% of cellulose + 2.5% inulin (CEIN_5%); group 3 received AIN 93G containing 2.5% of cellulose + 2.5% taioba fiber (CETA_5%); group 4 received AIN 93G containing 5% cellulose + 2.5% taioba fiber (CETA_7.5%); group 5 received AIN 93G containing 5% cellulose + 2.5% of inulin (CEIN_7.5%). LTL showed high contents of total fiber, predominantly comprising insoluble DF with glucose as the major monomer. Rats receiving LTL had increased fecal mass and fat excretion, and improved BA profiles by diminishing the proportion of secondary acids, thus suggesting that consumption of taioba leaf may have the property of lowering the risk of colon cancer.