Pectin from sunflower by-products obtained by ultrasound: Chemical characterization and in vivo evaluation of properties in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a public health challenge and the use of pectin for symptom amelioration is a promising option. In this work, sunflower pectin has been extracted without (CHP) and with assistance of ultrasound (USP) using sodium citrate as a food-grade extracting agent. At optimal conditions (64 ◦C, 23 min) the highest yield was obtained with ultrasound application (15.5 vs. 8.1 %). Both pectins were structurally characterized by 1H NMR, HPSEC-ELSD, FT-IR and GC-FID. Unlike CHP, USP showed a lower molecular weight, higher galacturonic acid, lower degree of methyl-esterification and, overall, higher viscosity. These characteristics could affect the anti-inflammatory activity of pectins, evaluated using DSS-induced IBD model mice. So, USP promoted the defence (ICAM-1) and repair of the gastrointestinal mucosa (TFF3, ZO-1) more effectively than CHP. These results demonstrate the potential amelioration of acute colitis in IBD mice through USP supplementation. Taking into account the biomarkers analysed, these results demonstrate, for the first time, the positive impact of sunflower pectin extracted by ultrasound under very soft conditions on inflammatory bowel disease that might open up new possibilities in the treatment of this serious pathologyMINECO of Spain, Project AGL2014- 53445-RGrant PID2021-123862OB-I00 funded by MCIN/AEI/ 10.13039/501100011033ERDF A way of making EuropePFIS (FI20/00159) from the Instituto de Salud Carlos IIIMinistry of Economy of Spai

Effect of a Ropy Exopolysaccharide-Producing Bifidobacterium animalis subsp. lactis Strain Orally Administered on DSS-Induced Colitis Mice Model

Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes

In Vitro Antimicrobial, Antiviral and Cytotoxicity Activities of Aspergillus oryzae Isolated From El-Baida Marsh in Algeria

This work covers the study of antimicrobial and antiviral activities of the Aspergillus oryzae strain isolated from saline soil (El-Baida marsh in Algeria). The crude extract obtained with ethyl acetate displayed antimicrobial activity against Gram-positive and Gram-negative bacteria and the yeast Candida albicans with a mean of 16.69 mm of inhibition zone and a minimal inhibitory concentrations MICs between 7.28 and 21.85 μgmL-1. We also assessed the antiviral activity against Herpes simplex-2 Virus (HSV-2), in which no inhibitory effect was exhibited. In addition, cytotoxicity activity was tested in Caco-2 and RAW 264, a human epithelial and a murine macrophage cell line, respectively, revealing a no-toxic effect of the extract. The studied isolate extract possesses an antimicrobial property and its non-toxicity to the host cells becomes very important, and can be exploited for the production of new pharmacological and biotechnological agents.        Keywords: Aspergillus oryzae, antimicrobial activity, antiviral activity, cytotoxicity, fungal extraction

Intestinal anti-inflammatory effects of artichoke pectin and modified pectin fractions in the dextran sulfate sodium model of mice colitis. Artificial neural network modelling of inflammatory markers

Anti-inflammatory properties of artichoke pectin and modified fractions (arabinose- and galactose-free) used at two doses (40 and 80 mg kg−1) in mice with colitis induced by dextran sulfate sodium have been investigated. Expression of pro-inflammatory markers TNF-α and ICAM-I decreased in groups of mice treated with original and arabinose-free artichoke pectin while IL-1β and IL-6 liberation was reduced only in mice groups treated with original artichoke pectin. A decrease in iNOS and TLR-4 expression was observed for most treatments. Intestinal barrier gene expression was also determined. MUC-1 and Occludin increased in groups treated with original artichoke pectin while MUC-3 expression also increased in arabinose-free pectin treatment. Galactose elimination led to a loss of pectin bioactivity. Characteristic expression profiles were established for each treatment through artificial neural networks showing high accuracy rates (≥90%). These results highlight the potential amelioration of inflammatory bowel disease on mice model colitis through artichoke pectin administration.This work has been funded by MICINN of Spain, Projects AGL2014-53445-R and AGL2017-84614-C2-1-R. Carlos Sabater thanks his FPU Predoc contract from Spanish MECD (FPU14/ 03619)

Intestinal anti-inflammatory effects of artichoke pectin and modified pectin fractions in the dextran sulfate sodium model of mice colitis. Artificial neural network modelling of inflammatory markers

Anti-inflammatory properties of artichoke pectin and modified fractions (arabinose- and galactose-free) used at two doses (40 and 80 mg kg−1) in mice with colitis induced by dextran sulfate sodium have been investigated. Expression of pro-inflammatory markers TNF-α and ICAM-I decreased in groups of mice treated with original and arabinose-free artichoke pectin while IL-1β and IL-6 liberation was reduced only in mice groups treated with original artichoke pectin. A decrease in iNOS and TLR-4 expression was observed for most treatments. Intestinal barrier gene expression was also determined. MUC-1 and Occludin increased in groups treated with original artichoke pectin while MUC-3 expression also increased in arabinose-free pectin treatment. Galactose elimination led to a loss of pectin bioactivity. Characteristic expression profiles were established for each treatment through artificial neural networks showing high accuracy rates (≥90%). These results highlight the potential amelioration of inflammatory bowel disease on mice model colitis through artichoke pectin administration.This work has been funded by MICINN of Spain, Projects AGL2014-53445-R and AGL2017-84614-C2-1-R. Carlos Sabater thanks his FPU Predoc contract from Spanish MECD (FPU14/ 03619)

Metformin and its redox-related mechanisms of action in type 2 diabetes

Type 2 diabetes (T2D) is a long-term metabolic disease characterized by progressive β-cell functional decline and insulin resistance, which increases the risk of cardiovascular complications as well as associated-morbidity and mortality. Evidence suggests a strong relationship between hyperglycaemia, oxidative stress and the development and progression of T2D. Indeed, a hyperglycaemic state can reduce the activity of antioxidant enzymes and increase lipid peroxidation and protein oxidation products, as well as DNA damage. At present, metformin is the recommended first-line glucose-lowering agent in patients with T2D. Despite the vast clinical experience gained over several decades of use, several mechanisms of action of metformin have yet to be fully elucidated. This review provides an overview of the existing literature concerning the complicated interplay between oxidative stress and T2D and the molecular mechanisms underlying the redox-related mechanisms of action of metformin, which include (but are not limited to) interaction with AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms, inhibition of gluconeogenesis and action on leukocyte–endothelium interactions

Effect of a ropy Exopolysaccharide-producing Bifidobacterium animalis subsp. Lactis strain orally administered on dss-induced colitis mice model

Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes.This work was partially financed by FEDER European Union funds through the projects AGL2012-33278 and SAF2011-29648 of the Spanish Ministry of Economy and Competitiveness (MINECO), as well as to the projects AGR-6826 and CTS-164 of the “Junta de Andalucía.” CH acknowledges his FPI fellowship to MINECO and FA acknowledges her fellowship to Junta de Andalucía. The CIBEREHD is funded by the “Instituto de Salud Carlos III.”Peer Reviewe

Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract from Fumaria capreolata

Fumaria capreolata is used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts of Fumaria capreolata (AFC) on LPS-induced production of proinflammatory mediators (IL-6, IL-1β, iNOS, TNF-α, COX-2, and MIP-2) in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO) and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1β, iNOS, TNF-α, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis

Flavonoids in Inflammatory Bowel Disease: A Review

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients’ life quality and requires sustained pharmacological and surgical treatments. Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects.This work was supported by Junta de Andalucia (P10-AGR-6826 and CTS 164) and by the Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R) with funds from the European Union.The CIBER-EHD is funded by the Instituto de Salud Carlos III

Intestinal anti-inflammatory and visceral analgesic effects of a Serpylli herba extract in an experimental model of irritable bowel syndrome in rats

Ethnopharmacological relevance: Serpylli herba extract (SHE), composed of the aerial parts of wild thyme (Thymus serpyllum L.) (Lamiaceae family), is traditionally used in Europe and North Africa to treat diarrhea, gastric ulcers, intestinal parasites and upper respiratory tract infections. Recently, SHE has generated a great interest for irritable bowel syndrome (IBS) management, probably due to its intestinal anti-inflammatory properties shown in experimental colitis and the fact that its active components could preserve the intestinal barrier integrity, which is altered in patients with IBS. Aim of study: We aimed to test the effects of a SHE in a rat experimental model resembling human IBS. Materials and methods: IBS was provoked by deoxycholic acid (DCA). Rats were then treated with SHE (100 mg/kg) or gabapentin (70 mg/kg) and different inflammatory and gut barrier integrity markers were evaluated. Moreover, several gut hypersensitivity and hyperalgesia determinations were performed. Results: SHE improved referred pain and visceral hypersensitivity. Additionally, SHE enhanced immune status by downregulating of the expression of the proinflammatory mediators Il-1β, Il-6, Ifn-γ, Tlr-4, and the inducible enzyme Cox-2, thus inducing visceral analgesia, and promoting the restore of the gut barrier function by upregulating the mucins Muc-2 and Muc-3. These antiinflammatory effects could be related to its action on mast cells since it significantly inhibited the β-Hexosaminidase production in RBL-2H3 cells. Lastly, SHE also seems to modulate the serotonin pathway by restoring the altered expression of the 5-HT receptors Htr-3 and Htr-4. Conclusion: SHE could be considered a potential new treatment for IBS, since it ameliorates hypersensitivity, visceral hyperalgesia, and inflammation. These beneficial effects may be due to the inhibition of mast cells degranulation and serotonin pathway.Junta de Andalucia AGR6826 CTS 164Spanish Government SAF 2011-29648Instituto de Salud Carlos IIIEuropean Commission PI19/01058 PI20/0144