The beneficial effects of various polyphenols with plant origins on different cardiovascular-associated disorders, such as hypertension, diabetes mellitus type 2 and metabolic syndrome are well ...known. Recently, marine crude-drugs are emerging as potential treatments in many noncommunicable conditions, including those involving the cardiovascular system. Among the active compounds responsible for these activities, seaweed polyphenols seem to play a key role. The aim of the present review is to summarise the current knowledge about the beneficial effects reported for edible seaweed polyphenols in the amelioration of these prevalent conditions, focusing on both preclinical and clinical studies. This review will help to establish the basis for future studies in this promising field.
As for other aromatic plants, there are many analytical methods for the determination of volatile compounds in lavender essential oils. Alternatively, in this study RP–HPLC–DAD–QTOF–MS was used for ...the profiling of the phytochemical constituents of hydromethanolic extracts of L. stoechas and L. dentata, which were obtained by pressurized liquid extraction. The spectrometric data revealed complex profiles constituted of a wide range of polar and semi‐polar phytochemicals, mainly, phenolic compounds (68). Most phenolic compounds (55) have not been previously reported in Lavandula; such is the case of caffeic acid‐based oligomers. Moreover, the analytical method was validated for the determination of phenolic compounds. Our findings showed both qualitative and quantitative differences between the extracts. In this sense, while hydroxycinnamic acids made up the largest class in both extracts, flavones were the most abundant class, accounting for 10.44 g (L. dentata) and 4.85 g (L. stoechas) per 100 g of dry extract. In conclusion, this analytical method provided essential information about the phytochemical composition of the studied medicinal plants, revealing novel constituents that were probably hidden for others. In addition, these results may help to understand the anti‐inflammatory properties of these extracts.
Background
Drug‐induced maculopapular exanthemas (MPEs) are mediated by Th1 CD4+ T cells. One of the mechanisms of control of Th1 cells in homeostasis is the interaction between the checkpoint ...inhibitor Tim3 and its physiological ligand galectin‐9 (Gal9). Disorders affecting this axis may be responsible for various autoimmune and immunological diseases. The aim of this study was to determinate the influence of the Tim3‐Gal9 axis on the development of MPE induced by drugs.
Methods
Frequencies of different cell subsets and the expression of Tim3 and Gal9 were measured in peripheral blood by flow cytometry and in skin biopsies by immunohistochemistry. Gal9 expression was assessed by RT‐qPCR; its release was measured by multiplex assay. The effects of blocking or enhancing the Tim3‐Gal9 axis on monocyte‐derived dendritic cell (moDC) maturation and T‐cell proliferation were determined by flow cytometry.
Results
The expression of Tim3 was significantly reduced in peripheral blood Th1 cells and in the skin of MPE patients vs controls. Gal9 expression and release were significantly reduced in patient peripheral blood and moDCs, respectively. The addition of exogenous Gal9 significantly reduced Tim3+ Th1 proliferation, although Treg proliferation increased.
Conclusion
This study showed the involvement of the Tim3‐Gal9 axis in MPE. The reduced expression of Tim3 in Th1 cells together with the impaired expression of Gal9 in PBMCs and DCs appears to have a role in the development of the disease. The potential of Gal9 to suppress Th1 and enhance Treg proliferation makes it a promising tool for treating these reactions.
The reduced level of the checkpoint molecule Tim3 in Th1 cells together with the impaired expression of Gal9 in PBMCs and dendritic cells hampers the control of Th1 cell numbers in patients with drug‐induced maculopapular exanthema (MPE). The reduced expression of Gal9 in patients with drug‐induced MPE could be responsible for the low frequencies of Treg cells in these patients. Exogenous administration of Gal9 could be a potential therapeutic tool able to suppress Th1 and enhance Treg differentiation in patients with drug‐induced MPE.
Scope
Much of the knowledge about gene expression during anaphylaxis comes from candidate gene studies. Despite their potential role, expression changes in dendritic cells (DCs) have not been studied ...in this context using high throughput methods. The molecular mechanisms underlying food‐antigen‐induced anaphylaxis are investigated using DCs from an animal model.
Methods and results
RNA sequencing is used to study gene expression in lymph‐node‐derived DCs from anaphylactic mice sensitized intranasally with the major peach allergen Pru p 3 during the acute reaction phase, induced intraperitoneally. In total, 237 genes changed significantly, 181 showing at least twofold changes. Almost three‐quarters of these increase during anaphylaxis. A subset is confirmed using RT‐PCR in a second set of samples obtained from a new batch of mice. Enrichment analysis shows an overrepresentation of genes involved in key immune system and inflammatory processes, including TGF‐β signaling. Comparison with a study using anaphylactic human subjects show significant overlap.
Conclusions
The findings provide a comprehensive overview of the transcriptional changes occurring in DCs during anaphylaxis and help elucidate the mechanisms involved. They add further weight to the putative role of these cells in anaphylaxis and highlight genes that may represent potential therapeutic targets.
Mice are sensitized to the major peach allergen Pru p 3 using a previously published protocol. Upon challenge with the specific allergen, they underwent an anaphylactic reaction. Dendritic cells are isolated from their lymph nodes, from which RNA is extracted and sequenced, comparing the results to non‐anaphylactic, non‐sensitized mice to look for differences in gene expression in a high‐throughput manner. Differential expression is found for over 200 genes and multiple immune pathways, including complement activation, LPS signaling, and TGF‐β pathways.
Aim
High blood pressure (BP) is associated with gut microbiota dysbiosis. The aim of this study was to investigate whether changes in gut microbiota induced by exchanging the gut microbiota between ...spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) alter the gut‐immune system interaction inducing changes in vascular function and BP.
Methods
Twenty‐week‐old recipient WKY and SHR were orally gavaged with donor faecal contents from WKY or SHR. In additional experiments, we used a design to determine whether blockade of B7‐dependent costimulation with CTLA4‐Ig or blockade of IL‐17 with IL‐17‐neutralizing antibody could prevent hypertension caused by faecal microbiota transplantation (FMT) from SHR to WKY.
Results
Correlation analyses identified the bacterial abundance of Turicibacter and S24‐7_g that, respectively, positively and negatively correlated with systolic BP. FMT from WKY rats to SHR rats reduced basal systolic BP, restored the imbalance between Th17/Treg in mesenteric lymph nodes (MLNs) and aorta, and improved endothelial dysfunction and vascular oxidative status found in SHR transplanted with SHR faeces. FMT from SHR to WKY increased CD80 and CD86 mRNA levels and T cells activation in MLNs, circulating T cells, aortic T cell infiltration, impaired endothelial function and increased basal SBP. These effects were abolished by blockade of B7‐dependent costimulation with CTLA4‐Ig. IL‐17a neutralizing antibody reduced SBP and improved endothelial dysfunction induced by FMT from SHR to WKY.
Conclusion
Gut microbiota is an important factor involved in the control of BP, as a consequence of its effect in T‐cell activation in gut immune system and vascular T‐cells accumulation.
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders characterized by relapsing intestinal inflammation, but many details of pathogenesis remain to be fully unraveled. Glucocorticoid ...(GC)‐induced leucine zipper (GILZ) is a mediator of the anti‐inflammatory effects of GCs, the most powerful drugs for IBD treatment, but they cause several unwanted side effects. The fusion protein TAT‐GILZ has been successfully used in some pre‐clinical models of inflammatory and autoimmune diseases. To test the efficacy of TAT‐GILZ for treating dextran sulfate sodium (DSS)‐induced colitis and explore its impact on the gut microbiome, colitis was induced by DSS in C57BL/6J mice and treated with TAT‐GILZ or dexamethasone. Various hallmarks of colitis were analyzed, including disease activity index, gut permeability, and expression of pro‐inflammatory cytokines and tight junction proteins. TAT‐GILZ treatment showed a therapeutic effect when administered after the onset of colitis. Its efficacy was associated with improved gut permeability, as evidenced by zonula occludens‐1 and CD74 upregulation in inflamed colonic tissue. TAT‐GILZ also ameliorated the changes in the gut microbiota induced by the DSS, thus potentially providing an optimal environment for colonization of the mucosa surface by beneficial bacteria. Overall, our results demonstrated for the first time that TAT‐GILZ treatment proved effective after disease onset allowing restoration of gut permeability, a key pathogenic feature of colitis. Additionally, TAT‐GILZ restored gut dysbiosis, thereby contributing to healing mechanisms. Interestingly, we found unprecedented effects of exogenous GILZ that did not overlap with those of GCs.
ABSTRACTThe aim of the present study was to examine whether the immune‐modulatory bacteria Lactobacillus fermentum CECT5716 (LC40) ameliorates disease activity and cardiovascular complications in a ...female mouse model of lupus. Eighteen‐week‐old NZBWF1 systemic lupus erythematosus (SLE) and NZW/LacJ (control) mice were treated with vehicle or LC40 (5 × 108 colony‐forming units/d) for 15 wk. LC40 treatment reduced lupus disease activity, blood pressure, cardiac and renal hypertrophy, and splenomegaly in SLE mice. LC40 reduced the elevated T, B, regulatory T cells (Treg), and T helper (Th)‐1 cells in mesenteric lymph nodes of lupus mice. LC40 lowered the higher plasma concentration of proinflammatory cytokines observed in lupus mice. Aortas from SLE mice showed reduced endothelium‐dependent vasodilator responses to acetylcholine. Endothelial dysfunction found in SLE is related to an increase of both NADPH oxidase‐driven superoxide production and eNOS phosphorylation at the inhibitory Thr495. These activities returned to normal values after a treatment with LC40. Probiotic administration to SLE mice reduced plasma LPS levels, which might be related to an improvement of the gut barrier integrity. LC40 treatment increases the Bifidobacterium count in gut microbiota of SLE mice. In conclusion, our findings identify the gut microbiota manipulation with LC40 as an alternative approach to the prevention of SLE and its associated vascular damage.—Toral, M., Robles‐Vera, I., Romero, M., de la Visitación, N., Sánchez, M., O'Valle, F., Rodriguez‐Nogales, A., Gálvez, J., Duarte, J., Jiménez, R. Lactobacillus fermentum CECT5716: a novel alternative for the prevention of vascular disorders in a mouse model of systemic lupus erythematosus. FASEB J. 33, 10005–10018 (2019). www.fasebj.org
Scope
To compare the intestinal anti‐inflammatory effects of two probiotics Lactobacillus fermentum and Lactobacillus salivarius in mouse colitis, focusing on their impact on selected miRNAs and ...microbiota composition.
Methods and results
Male C57BL/6J mice were randomly assigned to four groups (n = 10): non‐colitic, DSS colitic and two colitic groups treated with probiotics (5 × 108 CFU/mouse/day). Both probiotics ameliorated macroscopic colonic damage. They improved the colonic expression of markers involved in the immune response, and the expression of miR‐155 and miR‐223. L. fermentum also restored miR‐150 and miR‐143 expression, also linked to the preservation of the intestinal barrier function. Besides, these beneficial effects were associated with the amelioration of the microbiota dysbiosis and a recovery of the SCFAs‐ and lactic acid‐producing bacterial populations, although only L. fermentum improved Chao richness, Pielou evenness and Shannon diversity. Moreover, L. fermentum also restored the Treg cell population in MLNs and the Th1/Th2 cytokine balance.
Conclusion
Both probiotics exerted intestinal anti‐inflammatory effects in DSS‐mouse colitis, maybe due to their ability to restore the intestinal microbiota homeostasis and modulate the immune response. L. fermentum showed a greater beneficial effect compared to L. salivarius, which makes it more interesting for future studies.
Lactobacillus fermentum and L. salivarius, exert intestinal anti‐inflammatory effects in mouse DSS colitis, maybe due to their ability to restore intestinal microbiota composition and modulate the immune response. L. fermentum improved more parameters than L. salivarius, which makes it more interesting for future studies.
Abdominal pain is a common feature in inflammatory bowel disease (IBD) patients, and greatly compromises their quality of life. Therefore, the identification of new therapeutic tools to reduce ...visceral pain is one of the main goals for IBD therapy. Minocycline, a broad-spectrum tetracycline antibiotic, has gained attention in the scientific community because of its immunomodulatory and anti-inflammatory properties. The aim of this study was to evaluate the potential of this antibiotic as a therapy for the management of visceral pain in dextran sodium sulfate (DSS)-induced colitis in mice. Preemptive treatment with minocycline markedly reduced histological features of intestinal inflammation and the expression of inflammatory markers (Tlr4, Tnfα, Il1ß, Ptgs2, Inos, Cxcl2, and Icam1), and attenuated the decrease of markers of epithelial integrity (Tjp1, Ocln, Muc2, and Muc3). In fact, minocycline restored normal epithelial permeability in colitic mice. Treatment with the antibiotic also reversed the changes in the gut microbiota profile induced by colitis. All these ameliorative effects of minocycline on both inflammation and dysbiosis correlated with a decrease in ongoing pain and referred hyperalgesia, and with the improvement of physical activity induced by the antibiotic in colitic mice. Minocycline might constitute a new therapeutic approach for the treatment of IBD-induced pain. PERSPECTIVE: This study found that the intestinal anti-inflammatory effects of minocycline ameliorate DSS-associated pain in mice. Therefore, minocycline might constitute a novel therapeutic strategy for the treatment of IBD-induced pain.
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