(-)-Epicatechin mitigates anxiety-related behavior in a mouse model of high fat diet-induced obesity.

Mounting evidence demonstrates that consumption of high fat diet (HFD) and subsequent development of obesity leads to alterations in cognition and mood. While obesity can affect brain function, consumption of select dietary bioactives may help prevent obesity-related cognitive decline. This study investigated the capacity of the dietary flavonoid (-)-epicatechin (EC) to mitigate HFD-induced obesity-associated alterations in memory and mood. Healthy 8-week old male C57BL/6J mice were maintained on either a control diet (10 kCal% from fat) or a HFD (45 kCal% from fat) and were supplemented with EC at 2 or 20 mg/kg body weight (B.W.) for a 24 week period. Between week 20 and 22, anxiety-related behavior, recognition memory, and spatial memory were measured. Underlying mechanisms were assessed by measuring the expression of selected genes in the hippocampus and by 16S rRNA sequencing and metabolomic analysis of the gut microbiota. 24 weeks of HFD feeding resulted in obesity, which was not affected by EC supplementation. HFD-associated increase in anxiety-related behavior was mitigated by EC in a dose-response manner and was accompanied by increased hippocampal brain-derived neurotrophic factor (BDNF), as well as partial or full restoration of glucocorticoid receptor, mineralocorticoid receptor and 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) expression. Higher EC dosage (20 mg/kg B.W.) also restored aberrant Lactobacillus and Enterobacter abundance altered by HFD and/or the associated obesity. Together, these results demonstrate how EC mitigates anxiety-related behaviors, revealing a connection between BDNF- and glucocorticoids-mediated signaling. Our findings link changes in the hippocampus and the gut microbiota in a context of HFD-induced obesity and anxiety.

Supplementation with cyanidin and delphinidin mitigates high fat diet-induced endotoxemia and associated liver inflammation in mice.

Consumption of high fat diets (HFD) and the associated metabolic endotoxemia can initiate liver inflammation and lipid deposition that with time can progress to non-alcoholic fatty liver disease (NAFLD). We previously observed that 14 weeks supplementation with the anthocyanidins cyanidin and delphinidin mitigated HFD-induced metabolic endotoxemia and liver insulin resistance, steatosis, inflammation and oxidative stress. This work investigated if a 4-week supplementation of mice with a cyanidin- and delphinidin-rich extract (CDRE) could mitigate or reverse HFD (60% calories from lard fat)-induced liver steatosis and inflammation. After a first 4-weeks period on the HFD, mice showed increased endotoxemia and activation of liver proinflammatory signaling cascades. Supplementation with CDRE between weeks 4 and 8 did not mitigate liver steatosis or the altered lipid and glucose plasma levels. However, CDRE supplementation reverted HFD-induced metabolic endotoxemia, in parallel with the mitigation of the overexpression of hepatic TLR2 and TLR4, and of the activation of: (i) NF-κB, (ii) AP-1 and upstream mitogen-activated kinases p38 and ERK1/2, and (iii) HIF-1. Thus, even a short-term consumption of cyanidin and delphinidin could help mitigate the adverse consequences, i.e. metabolic endotoxemia and associated liver inflammation, triggered by the regular consumption of diets rich in fat.

Biogenic selenium nanoparticles synthesized by Stenotrophomonas maltophilia SeITE02 loose antibacterial and antibiofilm efficacy as a result of the progressive alteration of their organic coating layer.

Increasing emergence of drug-resistant microorganisms poses a great concern to clinicians; thus, new active products are urgently required to treat a number of infectious disease cases. Different metallic and metalloid nanoparticles have so far been reported as possessing antimicrobial properties and proposed as a possible alternative therapy against resistant pathogenic microorganisms. In this study, selenium nanoparticles (SeNPs) synthesized by the environmental bacterial isolate Stenotrophomonas maltophilia SeITE02 were shown to exert a clear antimicrobial and antibiofilm activity against different pathogenic bacteria, either reference strains or clinical isolates. Antimicrobial and antibiofilm capacity seems to be strictly linked to the organic cap surrounding biogenic nanoparticles, although the actual role played by this coating layer in the biocidal action remains still undefined. Nevertheless, evidence has been gained that the progressive loss in protein and carbohydrate content of the organic cap determines a decrease in nanoparticle stability. This leads to an alteration of size and electrical properties of SeNPs along with a gradual attenuation of their antibacterial efficacy. Denaturation of the coating layer was proved even to have a negative effect on the antibiofilm activity of these nanoparticles. The pronounced antimicrobial efficacy of biogenic SeNPs compared to the denatured ones can - in first instance - be associated with their smaller dimensions. This study showed that the native organic coating layer of biogenic SeNPs functions in avoiding aggregation and maintaining electrostatic stability of the nanoparticles, thus allowing them to maintain efficient antimicrobial and antibiofilm capabilities.

Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity.

An increased permeability of the intestinal barrier is proposed as a major event in the pathophysiology of conditions characterized by chronic gut inflammation. This study investigated the capacity of pure anthocyanins (AC), and berry and rice extracts containing different types and amounts of AC, to inhibit tumor necrosis alpha (TNFα)-induced permeabilization of Caco-2 cell monolayers. Caco-2 cells differentiated into intestinal epithelial cell monolayers were incubated in the absence/presence of TNFα, with or without the addition of AC or AC-rich plant extracts (ACRE). AC and ACRE inhibited TNFα-induced loss of monolayer permeability as assessed by changes in transepithelial electrical resistance (TEER) and paracellular transport of FITC-dextran. In the range of concentrations tested (0.25-1 µM), O-glucosides of cyanidin, and delphinidin, but not those of malvidin, peonidin and petunidin protected the monolayer from TNFα-induced decrease of TEER and increase of FITC-dextran permeability. Cyanidin and delphinidin acted by mitigating TNFα-triggered activation of transcription factor NF-κB, and downstream phosphorylation of myosin light chain (MLC). The protective actions of the ACRE on TNFα-induced TEER increase was positively correlated with the sum of cyanidins and delphinidins (r2 = 0.83) content in the ACRE. However, no correlation was observed between TEER and ACRE total AC, malvidin, or peonidin content. Results support a particular capacity of cyanidins and delphinidins in the protection of the intestinal barrier against inflammation-induced permeabilization, in part through the inhibition of the NF-κB pathway.

Biogenic selenium nanoparticles: characterization, antimicrobial activity and effects on human dendritic cells and fibroblasts.

Tailored nanoparticles offer a novel approach to fight antibiotic-resistant microorganisms. We analysed biogenic selenium nanoparticles (SeNPs) of bacterial origin to determine their antimicrobial activity against selected pathogens in their planktonic and biofilm states. SeNPs synthesized by Gram-negative Stenotrophomonas maltophilia [Sm-SeNPs(-)] and Gram-positive Bacillus mycoides [Bm-SeNPs(+)] were active at low minimum inhibitory concentrations against a number of clinical isolates of Pseudomonas aeruginosa but did not inhibit clinical isolates of the yeast species Candida albicans and C. parapsilosis. However, the SeNPs were able to inhibit biofilm formation and also to disaggregate the mature glycocalyx in both P. aeruginosa and Candida spp. The Sm-SeNPs(-) and Bm-SeNPs(+) both achieved much stronger antimicrobial effects than synthetic selenium nanoparticles (Ch-SeNPs). Dendritic cells and fibroblasts exposed to Sm-SeNPs(-), Bm-SeNPs(+) and Ch-SeNPs did not show any loss of cell viability, any increase in the release of reactive oxygen species or any significant increase in the secretion of pro-inflammatory and immunostimulatory cytokines. Biogenic SeNPs therefore appear to be reliable candidates for safe medical applications, alone or in association with traditional antibiotics, to inhibit the growth of clinical isolates of P. aeruginosa or to facilitate the penetration of P. aeruginosa and Candida spp. biofilms by antimicrobial agents.

Oxidative stress and menopause-related hot flashes may be independent events.

OBJECTIVE: At present, there is growing demand for alternative, or additional, treatments to hormone replacement therapy for menopause-related hot flashes (HF). Antioxidant supplements have been recently proposed as possible candidates for this purpose, regardless of the absence of clear evidence in support of a link between these vasomotor symptoms and oxidative stress (OxS). The aim of our study was to evaluate the association between HF and OxS serum markers in a large sample of middle-aged women. MATERIALS AND METHODS: We conducted a cross-sectional study on 245 perimenopausal and early postmenopausal women (age 45-60 years). The variables examined were presence of self-reported HF and levels of 8-iso-prostaglandin F2α, 8-OH-deoxy-2'-guanosine, advanced oxidation protein products, total antioxidant power, uric acid, thiols, and paroxonase-1. RESULTS: Seventy-six women (31%) reported to suffer from HF (either medium or high intensity). None of the peripheral markers of OxS examined was found to be significantly associated with the presence of HF. CONCLUSION: Taken together, our data suggest that systemic OxS might not be implicated with the onset of the climacteric vasomotor symptoms that most commonly affect women experiencing perimenopause and early postmenopause.