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 different 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-α, Il-1β, Il-6 and increased the levels of adiponectin and AMPK, which exert anti-inflammatory effects. Moreover, Italia genotype ameliorated the intestinal barrier function. In conclusion, Filipina and Italia methanolic extracts show the highest antioxidant and anti-inflammatory effect, 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.
Immunomodulatory tetracyclines potentiate protective immune pathways leading to mucosal healing and resolution, representing a promising drug reposition strategy for the treatment of intestinal inflammation.
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract characterized by an exacerbated mucosal immune response. Macrophages play pivotal roles in the maintenance of gut homeostasis but they are also implicated in the pathogenesis of IBD. They are highly plastic cells and their activation state depends on the local environment. In the healthy intestine, resident macrophages display an M2 phenotype characterized by inflammatory energy, while inflammatory M1 macrophages dominate in the inflamed intestinal mucosa. In this regard, modifying the balance of macrophage populations into an M2 phenotype has emerged as a new therapeutic approach in IBD. Multipotent mesenchymal stromal cells (MSCs) have been proposed as a promising cell-therapy for the treatment of IBD, considering their immunomodulatory and tissue regenerative potential. Numerous preclinical studies have shown that MSCs can induce immunomodulatory macrophages and have demonstrated that their therapeutic efficacy in experimental colitis is mediated by macrophages with an M2-like phenotype. However, some issues have not been clarified yet, including the importance of MSC homing to the inflamed colon and/or lymphoid organs, their optimal route of administration or whether they are effective as living or dead cells. In contrast, the mechanisms behind the effect of MSCs in human IBD are not known and more data are needed regarding the effect of MSCs on macrophage polarization that would support the observation reported in the experimental models. Nevertheless, MSCs have emerged as a novel method to treat IBD that has already been proven safe and with clinical benefits that could be administered in combination with the currently used pharmacological treatments.
pro-inflammatory and oxidative mediators, chemokines, and cell adhesion molecules. This immunomodulatory property was proposed that one of the possible action mechanisms of extract. An improvement in intestinal damage was also associated with a reduction in oxidative stress and infiltration of leukocytes, as evidenced by the reduction in malonaldialdehyde and myeloperoxidase activity and increase in total glutathione in the colonic tissue. Moreover, the extract improved the cytoarchitecture of the colonic tissue and the integrity of the intestinal epithelial barrier by restoring the expression of the proteins associated with mucosa protection. In view of the beneficial effects showed by the B. pinnatum leaf extract in preclinical rodent models of colitis there is the potential to conduct some future clinical studies to ensure safe and effective development of a phytotherapeutic treatment for human inflammatory bowel diseases.
Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesity-associated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ẞ, Il-6, Tnf-α, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-α, Ppar-γ, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome.
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