Asymmetric Synthesis of Flavanols via Cu-Catalyzed Kinetic Resolution of Chromenes and Their Anti-Inflammatory Activity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE181052 | GEO | 2021/07/30
REPOSITORIES: GEO
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Project description:Introduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health
2018-04-25 | GSE84453 | GEO
Project description:Stryphnodendron pulcherrimum is a species known to have a high content of tannins. Accordingly, its preparations are used in southern Para, Brazil, for their anti-inflammatory and antimicrobial activities, but so far, its chemical profile composition remains essentially unknown. We herein describe the compounds present in a hydro-acetonic extract from S. pulcherrimum leaves as revealed by dereplication via ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry. The data were combined with spectral organization, spectral matching through the Global Natural Products Social platform, in silico annotation and taxonomical ponderation. Several types of phenolic compounds were identified such as gallic acids, flavan-3-ols and flavone-like compounds. From these, 5 have been recently reported by our group, whereas 44 are reported here for the first time in this tree species, and 41 (out of 49) for this genus. The results highlight the possible role of Stryphnodendron pulcherrimum as a renewable source for natural bioactive products with potential pharmaceutical applications.
2021-12-14 | MSV000088562 | MassIVE
Project description:The success of TNF inhibitors for treatment of psoriasis and other inflammatory diseases was previously attributed to blockade of innate immunity. In a clinical trial using etanercept TNF blocking agent to treat psoriasis vulgaris, we used affymetrix gene arrays to analyze broad gene profiles in lesional skin at multiple timepoints during drug treatment (baseline, and weeks 1, 2, 4 and 12) compared to non-lesional skin. This analysis created a temporal model of TNF-dependent gene regulation that informs molecular mechanisms of TNF-mediated inflammation. We identified four gene clusters that were differentially down-modulated during etanercept treatment: the cluster down-regulated most rapidly contained mostly dendritic cell activation genes. Culturing human keratinocytes with TNF, IFNg and IL-17 generated a list of keratinocyte genes regulated by each cytokine. The IL-17 pathway genes were strongly down-modulated early, whereas IFNg pathway genes were not down-modulated until final disease resolution at week 12. Finally, we show that TNF blockade rapidly inhibits IL-12/IL-23 p40 subunit expression, and that p40 neutralization inhibits psoriatic dermal émigré-mediated Th17 polarization. We hypothesize that etanercept inhibits myeloid dendritic cell production of IL-23, a Th17 survival cytokine, resulting in rapid downregulation of IL-17 pathway genes. This data links effects of TNF blockade on the innate immune system with the adaptive immune system. Keywords: time-course experiment
2009-10-30 | GSE11903 | GEO
Project description:The success of TNF inhibitors for treatment of psoriasis and other inflammatory diseases was previously attributed to blockade of innate immunity. In a clinical trial using etanercept TNF blocking agent to treat psoriasis vulgaris, we used affymetrix gene arrays to analyze broad gene profiles in lesional skin at multiple timepoints during drug treatment (baseline, and weeks 1, 2, 4 and 12) compared to non-lesional skin. This analysis created a temporal model of TNF-dependent gene regulation that informs molecular mechanisms of TNF-mediated inflammation. We identified four gene clusters that were differentially down-modulated during etanercept treatment: the cluster down-regulated most rapidly contained mostly dendritic cell activation genes. Culturing human keratinocytes with TNF, IFNg and IL-17 generated a list of keratinocyte genes regulated by each cytokine. The IL-17 pathway genes were strongly down-modulated early, whereas IFNg pathway genes were not down-modulated until final disease resolution at week 12. Finally, we show that TNF blockade rapidly inhibits IL-12/IL-23 p40 subunit expression, and that p40 neutralization inhibits psoriatic dermal emigre-mediated Th17 polarization. We hypothesize that etanercept inhibits myeloid dendritic cell production of IL-23, a Th17 survival cytokine, resulting in rapid downregulation of IL-17 pathway genes. This data links effects of TNF blockade on the innate immune system with the adaptive immune system. Experiment Overall Design: In this study 15 patients with moderate-to-severe psoriasis were given 50mg of etanercept (Amgen) biweekly for 12 weeks. And analyzed using gene array on mRNA extracted from tissue collected at each biopsy time point (non-lesional Time: 0; lesional Time: 0, weeks 1, 2, 4, and 12). Patients were stratified as 'responders' or 'non-responders' based on whether or not they achieved histologic disease resolution by week 12 of etanercept treatment (decreased epidermal thickening, normalization of proliferation marker Ki67, and loss of differentiation marker K16).
2009-11-09 | E-GEOD-11903 | biostudies-arrayexpress
Project description:Anorexia can occur as a serious complication of chronic disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. We studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after an intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. C57BL/6 mice were intraperitoneally injected with TNFalpha, IL-6 Low, IL-6 High, combination TNF+IL-6 Low or combination TNF+IL-6 High. Each group comprised of 12 animals, of which 6 animals were used for transcriptomics.
2016-05-31 | E-GEOD-69151 | biostudies-arrayexpress
Project description:Cytokines such as TNF-alpha and IL-1beta are known for their contribution to inflammatory processes in liver . In contrast, the cytokine IL-17 has not yet been assigned a role in liver diseases. IL-17 can cooperate with TNF-alpha to induce a synergistic response on several target genes in different cell lines, but no data exist for primary hepatocytes. To enhance our knowledge on the impact of IL-17 alone and combined with TNF-alpha in primary murine hepatocytes a comprehensive microarray study was designed. IL-1beta was included as this cytokine is suggested to act in a similar manner as the combination of TNF-alpha and IL-17, especially with respect to its role in mRNA stabilization. Results: The present microarray analysis demonstrates that primary murine hepatocytes responded to IL-17 stimulation by upregulation of chemokines and genes, which are functionally responsible to increase and sustain inflammation. Cxcl2, Nfkbiz and Zc3h12a were strongly induced, whereas the majority of the genes were only very moderately upregulated. Promoter analysis revealed involvement of NF-kappaB in the activation of many genes. Combined stimulation of TNF-alpha/IL-17 resulted in enhanced induction of gene expression, but significantly synergistic effects could be applied only to a few genes, such as Nfkbiz, Cxcl2, Zc3h12 and Steap4. Comparison of the gene expression profile obtained after stimulation of TNF-alpha/IL-17 versus IL-1 proposed a IL-1beta-like effect of the latter cytokine combination. Moreover, evidence was provided that modulation of mRNA stability may be a major mechanism by which IL-17 regulates gene expression in primary hepatocytes. This assumption was exemplarily proven for Nfkbiz mRNA for the first time in hepatocytes. Our studies also suggest that RNA stability can partially be correlated to the existence of AU rich elements, but further mechanisms like the RNase-activity of the upregulated Zc3h12a have to be considered. Conclusions: Our microarray analysis gives new insights in IL-17 induced gene expression in primary hepatocytes highlighting the crosstalk with the NF-kappaB signalling pathway. Gene expression profile suggests IL-17 a role in sustaining liver inflammatory processes most likely by RNA stabilization. Altogether, our results provide evidence that IL-17 alone and in concert with TNF-alpha may play a role in inflammatory liver diseases. Primary murine hepatocytes of three animals stimulated for 1 or 4h by TNF-alpha, IL-1beta, IL-17 or TNF-alpha followed by IL-17 were used for microarray analysis.
2010-03-07 | E-GEOD-19272 | biostudies-arrayexpress
Project description:A double cropping system has been commercially adopted in subtropical regions in southern China, where there is abundant sunshine and heat resources. In this viticulture system, the first growing season normally starts as a summer cropping cycle; then, the vine is pruned and forced by hydrogen cyanamide, resulting in a second crop in January of the next year. Due to climate differences between the two growing seasons, flavonoid content and composition varies greatly. In this study, changes in the transcriptome of flavonoid-associated pathways were compared in berries grown under the double cropping system; in addition, the accumulation of flavonoid compounds was compared. Specific alterations in MYB transcription factors occurred in winter cropping berries around veraison. Then, the winter cropping cycle distinctly induced the flavonoid metabolic pathways while triggering the ripening-associated pathways. Notably, the climate conditions in winter cropping positively affected flavonoid biosynthesis, while the summer season took a major toll on anthocyanin accumulation. In addition, the three classes of flavonoid compounds responded differently to the changing climate; the anthocyanins and flavonols were promoted several fold, whereas no consistent increase was found for flavan-3-ols. Conclusively, flavonoid biosynthesis in grapes grown under a double cropping system showed seasonal or climatic-specific accumulation patterns.
2017-10-01 | GSE103226 | GEO
Project description:Objectives: Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Methods: Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. Results: PNLA reduced percentage of monocytes expressing cytokines: TNF-a by 23% (p=0.048), IL-6 by 25% (p=0.011), IL-1B by 23% (p=0.050), IL-8 by 20% (p=0.066). Pathway analysis identified upstream activation of peroxisomes proliferator-activated receptors (PPARs), sirtuin3, and let7miRNA, KLF15 which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-a, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p=9.14E-09) and mitochondrial dysfunction (p=4.18E-08), while the sirtuin (SIRTs) signalling pathway was activated (p=8.89E-06) which interfere with the pathophysiologic process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and Acetyl-CoA Acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. Conclusion: PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.
2022-03-24 | E-MTAB-11585 | biostudies-arrayexpress
Project description:In this study, we sought to determine how IL-17 and TNF influence normal human melanocytes, either alone, or with both cytokines together. We reveal a dichotomous effect of IL-17 and TNF, which not only elicit essential mitogenic cytokines but also suppress melanogenesis by down-regulating genes of melanogenesis pathway Comparison of one batch of primary human melanocyte line cultured in serum free media, treated with TNF and/or IL-17, for either 24 or 48 hours.
2013-06-15 | E-GEOD-40413 | biostudies-arrayexpress
Project description:We sought to provide a comprehensive evaluation of the effects of TNF-α and IL-17 on the keratinocyte gene profile in order to identify genes that might be co-regulated by these cytokines. We then sought to determine how genes that were synergistically activated by both cytokines relate to the psoriasis transcriptome. Here, we identified 160 unique genes that were synergistically up-regulated by IL-17 and TNF-α and 188 unique genes where the two cytokines had at least an additive effect. Among highly up-regulated genes were those involved in neutrophil and lymphocyte chemotaxis, inflammation, and epidermal differentiation. Synergistically up-regulated genes included some of the highest expressed genes in lesional psoriatic skin with an impressive correlation between IL-17/TNF-α induced genes and the psoriasis gene signature. In conclusion, keratinocytes may be key drivers of pathogenetic inflammatory circuits in psoriasis through integrating responses to TNF-α and IL-17. This may explain high efficacy of targeting psoriasis with either anti-TNF-α or agents that block Th17 T-cells/IL-17 and has important implications for the development of new therapeutic agents. Comparison of keratinocyte responses to IL-17, TNF-α (1 ng mL-1 and 10 ng mL-1), and the combination of both cytokines in psoriasis.
2010-11-24 | E-GEOD-24767 | biostudies-arrayexpress