Reduction of colonic inflammation in HLA-B27 transgenic rats by feeding Marie Ménard apples, rich in polyphenols

Inflammatory bowel diseases (IBD) are immunomediated ailments affecting millions of individuals. Although diet is regarded as an important factor influencing IBD, there are no accepted dietary recommendations presently available. We administered 7.6 % lyophilised apples obtained from two cultivars (Golden Delicious and Marie Ménard, low and high in polyphenols, respectively) to HLA-B27 transgenic rats which develop spontaneous IBD. After 3 months feeding, rats fed Marie Ménard apples had reduced myeloperoxidase activity (3.6 (sem 0.3) v. 2.2 (sem 0.2) U/g tissue; P <0.05) and reduced cyclo-oxygenase-2 (P <0.05) and inducible NO synthase gene expression (P <0.01) in the colon mucosa and significantly less diarrhoea (P <0.05), compared with control rats. Cell proliferation in the colon mucosa was reduced significantly by feeding Golden Delicious apples, with a borderline effect of Marie Ménard apples. Gene expression profiling of the colon mucosa, analysed using the Whole Rat Genome 4 x 44 K Agilent Arrays, revealed a down-regulation of the pathways of PG synthesis, mitogen-activated protein kinase (MAPK) signalling and TNFalpha-NF-kappaB in Marie Ménard-fed rats. In the stools of the animals of this group we also measured a significant reduction of bacteria of the Bacteriodes fragilis group. In conclusion, the administration of Marie Ménard apples, rich in polyphenols and used at present only in the manufacturing of cider, ameliorates colon inflammation in transgenic rats developing spontaneous intestinal inflammation, suggesting the possible use of these and other apple varieties to control inflammation in IBD patient

Analysis of oxidative stress-related markers in Crohn&#8217;s disease patients at surgery and correlations with clinical findings

Crohn&rsquo; disease (CD) patients are at high risk of postoperative recurrence and new tools for the assessment of disease activity are needed to prevent long-term complications. In these patients, the over-production of ROS generated by inflamed bowel tissue and inflammatory cells activates a pathogenic cascade that further exacerbates inflammation and leads to increased oxidative damage to DNA, proteins, and lipids. We measured the products of protein/lipid oxidation and the total antioxidant capacity (ferric reducing ability of plasma, FRAP) in the serum of CD patients with severe disease activity requiring surgery with the aim to characterize their redox status and identify associations between oxidative stress-related markers and their clinical characteristics. At the systemic level, CD was associated with increased levels of protein and lipid oxidation products when compared to healthy volunteers, even though the FRAP values were similar. Advanced oxidation protein product (AOPP) levels showed the highest difference between patients and the controls (11.25, 5.02&ndash;15.15, vs. 1.36, 0.75&ndash;2.70, median, interquartile range; p &lt; 0.0001) and the analysis of receiver operating characteristic (ROC) curves, indicated for AOPP, the best area under the curve (AUC) value for CD prediction. Advanced glycated end-products (AGEs) were also significantly higher in CD patients (p &lt; 0.01), which is of interest since AOPP and AGEs are both able to activate the membrane receptor for advanced glycation end products (RAGE) involved in inflammatory diseases. Thiobarbituric acid reactive substance (TBARS) levels were significantly higher in CD patients with ileal localization and aggressive disease behavior, in smokers, and in patients suffering from allergies. In conclusion, our data indicate that circulating oxidative stress biomarkers may be attractive candidates as disease predictors as well as for clinical or therapeutic monitoring of CD. Our results also suggest that AOPP/AGEs and RAGE signaling may represent a pathogenic factor and a potential therapeutic target in CD

Tisochrysis lutea F&M-M36 Mitigates Risk Factors of Metabolic Syndrome and Promotes Visceral Fat Browning through β3-Adrenergic Receptor/UCP1 Signaling

Pre-metabolic syndrome (pre-MetS) may represent the best transition phase to start treatments aimed at reducing cardiometabolic risk factors of MetS. In this study, we investigated the effects of the marine microalga Tisochrysis lutea F&amp;M-M36 (T. lutea) on cardiometabolic components of pre-MetS and its underlying mechanisms. Rats were fed a standard (5% fat) or a high-fat diet (20% fat) supplemented or not with 5% of T. lutea or fenofibrate (100 mg/Kg) for 3 months. Like fenofibrate, T. lutea decreased blood triglycerides (p &lt; 0.01) and glucose levels (p &lt; 0.01), increased fecal lipid excretion (p &lt; 0.05) and adiponectin (p &lt; 0.001) without affecting weight gain. Unlike fenofibrate, T. lutea did not increase liver weight and steatosis, reduced renal fat (p &lt; 0.05), diastolic (p &lt; 0.05) and mean arterial pressure (p &lt; 0.05). In visceral adipose tissue (VAT), T. lutea, but not fenofibrate, increased the β3-adrenergic receptor (β3ADR) (p &lt; 0.05) and Uncoupling protein 1 (UCP-1) (p &lt; 0.001) while both induced glucagon-like peptide-1 receptor (GLP1R) protein expression (p &lt; 0.001) and decreased interleukin (IL)-6 and IL-1β gene expression (p &lt; 0.05). Pathway analysis on VAT whole-gene expression profiles showed that T. lutea up-regulated energy-metabolism-related genes and down-regulated inflammatory and autophagy pathways. The multitarget activity of T. lutea suggests that this microalga could be useful in mitigating risk factors of MetS

FROM PRECLINICAL TO CLINICAL EVIDENCE: EXPLORING THE MULTIPLE PERSPECTIVES AND HEALING POWER OF BOSWELLIA SERRATA ROXB. EX COLEBR

Boswellia serrata Roxb. ex Colebr. is a species belonging to the Burseraceae family, typical of dry environments of the Indian region. The oil-gum-resin, obtained from the trunk and thick branches, is known in phytotherapy for the volatile fraction which contains up to 70% terpenes. The most important and characteristic constituents are represented by pentacyclic triterpenes, named boswellic acids. B. serrata is known for multiple beneficial effects, mainly correlated to anti-inflammatory activity. This review aims to provide a comprehensive overview on the activities and potential applications of B. serrata based on clinical and preclinical evidence. An up-to-date literature review of preclinical and clinical studies related to the applications of B. serrata preparations in different pathological conditions was conducted using the main databases of scientific literature. A body of evidence point out the role of B. serrata extracts and its active constituents in the treatment of several inflammatory diseases. In particular, clinical trials revealed its use as a topical remedy of skin diseases, such as eczema and psoriasis, and internally in the treatment of asthma, intestinal and osteoarticular inflammatory diseases. Preclinical findings highlighted the positive effects of B. serrata extracts in cardiovascular and neurodegenerative diseases, and in cancer. Finally, B. serrata finds application as a feed additive in veterinary use. Although some limitations must be overcome, such as poor bioavailability, evidence supports that B. serrata is a promising medicinal plant. Furthermore, the use of B. serrata appears to have a favorable toxicological profile, but caution may be necessary regarding potential botanical-drug interactions

G14A-06- Analysis of the DORIS, GNSS, SLR, VLBI and Gravimetric Time Series at the GGOS Core Sites

Analysis of the time series at the 3-4 multi-technique GGOS sites to analyze and compare the spectral content of the space geodetic and gravity time series. Evaluate the level of agreement between the space geodesy measurements and the physical tie vectors

Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

The study aimed to assess the effects of polyphenols when used in combination with doxorubicin and etoposide, and to determine whether polyphenols sensitised leukaemia cells, causing inhibition of cell proliferation, cell cycle arrest and induction of apoptosis. This study is based on findings in solid cancer tumours, which have shown that polyphenols can sensitize cells to chemotherapy, and induce apoptosis and/or cell-cycle arrest. This could enable a reduction of chemotherapy dose and off-target effects, whilst maintaining treatment efficacy. Quercetin, apigenin, emodin, rhein and cis-stilbene were investigated alone and in combination with etoposide and doxorubicin in two lymphoid and two myeloid leukaemia cells lines. Measurements were made of ATP levels (using CellTiter-Glo assay) as an indication of total cell number, cell cycle progression (using propidium iodide staining and flow cytometry) and apoptosis (NucView caspase 3 assay and Hoechst 33342/propidium iodide staining). Effects of combination treatments on caspases 3, 8 and 9 activity were determined using Glo luminescent assays, glutathione levels were measured using the GSH-Glo Glutathione Assay and DNA damage determined by anti-γH2AX staining. Doxorubicin and etoposide in combination with polyphenols synergistically reduced ATP levels, induced apoptosis and increased S and/or G2/M phase cell cycle arrest in lymphoid leukaemia cell lines. However, in the myeloid cell lines the effects of the combination treatments varied; doxorubicin had a synergistic or additive effect when combined with quercetin, apigenin, emodin, and cis-stilbene, but had an antagonistic effect when combined with rhein. Combination treatment caused a synergistic downregulation of glutathione levels and increased DNA damage, driving apoptosis via caspase 8 and 9 activation. However, in myeloid cells where antagonistic effects were observed, this was associated with increased glutathione levels and a reduction in DNA damage and apoptosis. This study has demonstrated that doxorubicin and etoposide activity were enhanced by polyphenols in lymphoid leukaemia cells, however, differential responses were seen in myeloid cells with antagonistic responses seen in some combination therapies