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

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)

Calcium Pyruvate Exerts Beneficial Effects in an Experimental Model of Irritable Bowel Disease Induced by DCA in Rats

Pyruvate is a normal constituent of the body that participates in carbohydrate metabolism and functions as a scavenger of free radicals. Calcium pyruvate monohydrate (CPM) is a more stable derivative that has proved its anti-inflammatory effect in experimental colitis, among other disorders, and that could also be considered a source of calcium. Thus, it would be useful for the treatment of diseases with an inflammatory component and a high prevalence of osteoporosis like the irritable bowel syndrome (IBS). The aim of the present study is to evaluate the effects of CPM in a rat model of chronic post-inflammatory visceral pain induced by deoxycholic acid (DCA) that resembles IBS. Rats were administered DCA for three days intracolonically and then treated daily with CPM (40 and 100 mg/kg) or gabapentin (70 mg/kg) (positive control) by oral gavage for 17 days. The treatments reduced the visceral hypersensitivity measured by response to colorectal distension and referred pain. DCA induced changes in the colonic immune response characterized by increased expression of the cytokine Il-1b and the inducible enzyme Cox-2, which was reduced by the treatments. DCA also decreased the gut expression of the mucins Muc-2 and Muc-3, which was normalized by CPM, whereas gabapentin only increased significantly Muc-3. Moreover, DCA increased the expression of Tlr3, which was decreased to basal levels by all the treatments. However, the serotonin receptor Htr-4, which was also elevated, was not affected by any of the treatments, indicating no effect through this signalling pathway. In conclusion, CPM ameliorated the visceral hypersensitivity and the referred pain caused by DCA, being as effective as the control drug. Furthermore, it improved the immune status of the animals, which could contribute to the visceral analgesia and the regeneration of the intestinal epithelial barrier integrity.This work was supported by the Junta de Andalucía (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

Tigecycline reduces tumorigenesis in colorectal cancer via inhibition of cell proliferation and modulation of immune response

Junta de Andalucía (CTS 164)Instituto de Salud Carlos III (Spain)Fondo Europeo de Desarrollo Regional (FEDER)European Union, through the research grants PI18/00826, P18-RT-4930, PI0206–2016, PIE16/00045 and PI19/01058Spanish Ministry of Science and Innovation (MCIN/AEI/ 10.13039/501100011033/FEDER)RTI2018–101309-BC22Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963Spanish Ministry of Science and Innovation (“Programa de Doctorado: Medicina Clínica y Salud Pública” B12.56.1).Instituto de Salud Carlos III (FI17/00176)Junta de Andalucía (P18-RT-4930)University of GranadaCIBER-EHD is funded by the Instituto de Salud Carlos II

The Antioxidant Properties of Salvia verbenaca Extract Contribute to Its Intestinal Antiinflammatory Effects in Experimental Colitis in Rats

La enfermedad inflamatoria intestinal (EII) es una inflamación gastrointestinal crónica con fluctuaciones de síntomas impredecibles. Si bien no existe una cura eficaz para la EII, varios tratamientos tienen como objetivo controlar los síntomas y mejorar la calidad de vida de las personas afectadas. En los últimos años, ha habido un interés creciente en los beneficios potenciales de ciertas plantas y hierbas naturales en el tratamiento de la EII. En este sentido, este estudio tuvo como objetivo evaluar los efectos inmunomoduladores y antiinflamatorios de un extracto bien caracterizado de Salvia verbenaca (S. verbenaca) en un modelo experimental de colitis en ratas. Curiosamente, la administración diaria de S. verbenaca (10 y 25 mg/kg) alivió eficazmente los síntomas de la colitis, como lo demuestra la reducción de la relación peso/longitud y el daño colónico. Además, redujo los marcadores de estrés oxidativo (MPO y GSH), disminuyó la expresión de citocinas proinflamatorias (Il-6, Il-12a, Il-1β, Il-23, Icam-1, Mcp-1, Cinc-1) y conservó la integridad de la barrera intestinal (Villin, Muc-2, Muc-3). Estos efectos sugieren que el extracto de S. verbenaca podría representar un potencial candidato complementario para tratar los trastornos gastrointestinales. Sus acciones beneficiosas pueden estar relacionadas con sus propiedades antioxidantes, así como con la regulación negativa de la respuesta inmune, lo que puede resultar en la mejora de la barrera epitelial del intestino.Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammation with unpredictable symptom fluctuations. While there is no effective cure for IBD, various treatments aim to manage symptoms and improve the quality of life for affected individuals. In recent years, there has been growing interest in the potential benefits of certain natural plants and herbs in the management of IBD. In this regard, this study aimed to evaluate the immunomodulatory and anti-inflammatory effects of a well-characterized extract of Salvia verbenaca (S. verbenaca) in an experimental model of colitis in rats. Interestingly, the daily administration of S. verbenaca (10 and 25 mg/kg) effectively alleviated colitis symptoms, as evidenced by reduced weight/length ratio and colonic damage. Moreover, it reduced oxidative stress markers (MPO and GSH), decreased pro-inflammatory cytokine expression (Il-6, Il-12a, Il-1β, Il-23, Icam-1, Mcp-1, Cinc-1), and preserved the integrity of the intestinal barrier (Villin, Muc-2, Muc-3). These effects suggest S. verbenaca extract could represent a potential complementary candidate to treat gastrointestinal disorders. Its beneficial actions can be related to its antioxidant properties as well as the downregulation of the immune response, which can result in the improvement in the intestine epithelial barrier.Junta de Andalucia (AGR-6826)Junta de Andalucia (CTS-164)Ministerio de Economía y Competitividad (SAF2011-29648)Instituto de Salud Carlos III (pFIS (FI20/00159)Instituo de Saud Carlos III (Miguel Servet CP22/00153

Comparative Study of the Antioxidant and Anti-Inflammatory E ects of Leaf Extracts from Four Di erent Morus alba Genotypes in High Fat Diet-Induced Obesity in Mice

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.Increased levels of reactive oxygen species (ROS) and a low-grade chronic inflammation in multiple organs have been demonstrated in obesity. Morus alba leaves extracts (MAEs) have been used in traditional medicine as anti-inflammatory agents. In this work, the bioactive compounds of di erent genotypes of M. alba L. (Filipina, Valenciana Temprana, Kokuso, and Italia) were analyzed not only by reverse phase high performance liquid chromatography–electrospray ionization-time of flight-mass spectrometry (RP-HPLC-ESI-TOF-MS) and hydrophilic interaction chromatography–electrospray ionization-time of flight-mass spectrometry (HILIC-ESI-TOF-MS), but also screened for in vitro and in vivo antioxidant activity by means of DPPH radical scavenging assay and Caenorhabditis elegans model. These MAEs were administered daily in a model of diet-induced obesity in mice. Filipina and Italia genotypes significantly reduced weight gain, the glycemic levels in high fat diet, as well as, levels of LDL-cholesterol and triglycerides. Filipina and Italia MAEs also reduced the expression of proinflammatory mediators such as Tnf- , Il-1 , Il-6 and increased the levels of adiponectin and AMPK, which exert anti-inflammatory e ects. Moreover, Italia genotype ameliorated the intestinal barrier function. In conclusion, Filipina and Italia methanolic extracts show the highest antioxidant and anti-inflammatory e ect, due to the presence of compounds such as protocatechuic acid or quercetin-3-glucoside, and they could be developed as a complementary treatment for obesity and metabolic disorders.Junta de Andalucia CTS 164Spanish Ministry of Economy and Competitiveness AGL2015-67995-C3-3-REuropean Commission (FEDER/ERDF)ERDF/FEDER Operational Programme of the Region of Murcia 2007ES161PO001 14-20/20Instituto de Salud Carlos II

Silk fibroin nanoparticles enhance quercetin immunomodulatory properties in DSS-induced mouse colitis

This work has been supported from the European Commission ERDF/FEDER Operational Programme `Murcia' CCI N. 2007ES161PO001 (Project No. 14-20/20), the Junta de Andalucia (CTS164), Instituto de Salud Carlos III (PI19/01058) and the Spanish MINECO (Ref. CTQ201787708-R). P.D.-E. is a postdoctoral from Junta de Andalucia (European Commission FEDER); A.J.R.-M and L.H.-G. are predoctoral fellows from University of Granada ("Programa de Doctorado: Medicina Clinica y Salud Publica"); A.A.L.-P's research contract was supported by the ERDF/FEDER Operational Programme `Murcia' CCI N 2007ES161PO001 (Project No. 14-20/20); A.R.-N. is a postdoctoral fellow of Instituto de Salud Carlos III (Miguel Servet Program); T.V. is a postdoctoral fellow from Instituto de Investigación Biosanitaria de Granada.Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disorder affecting the gastrointes-tinal tract. The pharmacological treatments used currently for its treatment lack efficacy, so new therapeutic strategies should be developed. In this context, flavonoids loaded in biopolymeric nanoparticles can be considered as novel promising candidates. The aim of the present study was to evaluate the intestinal anti-inflammatory effects of quercetin when is administered loaded in silk fibroin nanoparticles (QSFN) in the dextran sulphate sodium experimental model of mouse colitis, which displays some similarities to human IBD. Previously characterized quercetin-loaded silk fibroin nanoparticles (QSFN). QSFN showed a reversible aggre-gation profile induced by the acidification of the solution but did not affect the loaded quercetin. Daily administration of QSFN significantly reduced disease activity index values compared to the control colitic group. This beneficial effect was not only corroborated by the histological examination of the colonic specimens but also the improvement of the colonic expression of the different proinflammatory cytokines (Tnf-alpha, Il-1 beta, Il-6, Mcp-1, Icam-1, Nlrp3 and iNOS). Therefore, these data suggest that QSFN could be a promising alternative to current treatments as a drug delivery system for IBD treatment.European Commission ERDF/FEDER Operational Programme `Murcia' CCI 2007ES161PO001- 14-20/20Junta de Andalucia CTS164Instituto de Salud Carlos III European Commission PI19/01058Spanish MINECO CTQ201787708-RERDF/FEDER Operational Programme 'Murcia' CCI 2007ES161PO001- 14-20/2

The Antioxidant Activity of Thymus serpyllum Extract Protects against the Inflammatory State and Modulates Gut Dysbiosis in Diet-Induced Obesity in Mice

Nowadays, there is an increasing interest in alternative therapies in the treatment of metabolic syndrome that combine efficacy and safety profiles. Therefore, this study aimed to evaluate the effect of an extract of Thymus serpyllum, containing rosmarinic acid, on high-fat diet (HFD)- induced obesity mice, highlighting the impact of its antioxidant activity on the inflammatory status and gut dysbiosis. The extract was administered daily (50, 100 and 150 mg/kg) in HFD-fed mice. The treatment reduced body weight gain, glucose and lipid metabolic profiles. Moreover, the extract ameliorated the inflammatory status, with the c-Jun N-terminal kinases (JUNK) pathway being involved, and showed a significant antioxidant effect by the reduction of radical scavenging activity and the mitigation of lipid peroxidation. Moreover, the extract was able to modulate the altered gut microbiota, restoring microbial richness and diversity, and augmenting the counts of short-chain fatty acid producing bacteria, which have been associated with the maintenance of gut permeability and weight regulation. In conclusion, the antioxidant activity of Thymus serpyllum extract displayed a positive impact on obesity and its metabolic alterations, also reducing systemic inflammation. These effects may be mediated by modulation of the gut microbiota.Junta de Andalucia CTS 164Instituto de Salud Carlos III European Commission PI19.01058Spanish Government AGL201567995-C3-3-REuropean CommissionInstituto de Salud Carlos II

Intestinal mesenchymal cells regulate immune responses and promote epithelial regeneration in vitro and in dextran sulfate sodium-induced experimental colitis in mice

This work was funded by the Junta de Andalucia (CTS 164) and by the Instituto de Salud Carlos III (Spain) and Fondo Europeo de Desarrollo Regional (FEDER), from the European Union, through the research grants PI18/00826, PI0206-2016 and PI19/01058. L.H-G and A.J.R-M are predoctoral fellows funded by the Spanish Ministry of Science and Innovation ("Programa de Doctorado: Medicina Clinica y Salud Publica" B12.56.1). J.A.M-T is a predoctoral fellow from the Instituto de Salud Carlos III (FI17/00176). P.A is supported by the Consejeria de Salud, Junta de Andalucia through the contract "Nicolas Monardes" (C-0013-2018). A. R-N is a postdoctoral fellow from the Instituto de Salud Carlos III (Miguel Servet program [CP19/00191]). CIBER-EHD is funded by the Instituto de Salud Carlos III.We would like to express our gratitude to Dr E. Aksoy and Dr L. Medrano Gonzalez (William Harvey Research Institute, Queen Mary University of London, London, UK) for providing us the cell line NCM356. Additionally, we thank Juan N. Moliz, Ana Santos and Mohamed Tassi of the Centre for Scientific Instrumentation (CIC, University of Granada) for their technical guidance and assistance.Aim Disruption of the intestinal mucosal tolerance, that is, the immunological unresponsiveness to innocuous food antigens and the commensal microbiota, in the colon is associated with several chronic diseases including inflammatory bowel disease (IBD). Understanding the mechanisms responsible for intestinal mucosal tolerance has potential translational value for its therapy and management. Human intestinal mesenchymal cells (iMCs) play important roles in colonic mucosal tolerance, but further studies on their tissue regenerative and immunomodulatory capacities are necessary in order to fully understand their function in health and disease. Methods In this study, we have isolated and analysed the capacity of human iMCs to promote wound healing and modulate immune responses in vitro and in vivo, using the dextran sulfate sodium (DSS)-induced colitis model. Results Cultured iMCs were CD45(-)CD73(+)CD90(+)CD105(+) and accelerated the wound closure in a normal colon mucosa (NCM) 356 human epithelial cell wound healing assay. Furthermore, iMCs blocked the LPS-mediated induction of TNF-alpha in THP-1 macrophages and inhibited the proliferation of peripheral blood mononuclear cells, partly through the induction of indoleamine-2,3-dioxygenase. In DSS colitic mice, iMCs administration reduced the disease activity index and ameliorated intestinal tissue damage and permeability. Furthermore, iMCs reduced intestinal inflammation, evidenced by a decreased mRNA expression of pro-inflammatory cytokines, reduced IL-1 beta secretion by intestinal explants and inhibited colonic iNOS protein expression. Conclusions Our data show that human iMCs isolated from the noninflamed intestine possess tissue-regenerative and immunomodulatory capacities that could potentially be harnessed/restored in order to reduce IBD severity.Junta de Andalucia CTS 164Instituto de Salud Carlos III European CommissionFondo Europeo de Desarrollo Regional (FEDER), from the European Union PI18/00826 PI0206-2016 PI19/01058Spanish Ministry of Science and Innovation ("Programa de Doctorado: Medicina Clinica y Salud Publica") B12.56.1Junta de Andalucia C-0013-2018Miguel Servet program CP19/00191Instituto de Salud Carlos III European Commissio