Anti-inflammatory dihydroxanthones from a Diaporthe species

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Markus Rohr ◽  
Anna Maria Kiefer ◽  
Ulrich Kauhl ◽  
Jonathan Groß ◽  
Till Opatz ◽  
...  
Keyword(s):  
Density Functional ◽  
Promoter Activity ◽  
Inflammatory Marker ◽  
Marker Gene ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory ◽  
Inducible Protein ◽  
Nfκb Pathway

Abstract In a search for anti-inflammatory compounds from fungi inhibiting the promoter activity of the small chemokine CXCL10 (Interferon-inducible protein 10, IP-10) as a pro-inflammatory marker gene, the new dihydroxanthone methyl (1R, 2R)-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1H-xanthene-1-carboxylate (2) and the previously described dihydroxanthone AGI-B4 (1) were isolated from fermentations of a Diaporthe species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy, mass spectrometry, and calculations using density functional theory (DFT). Compounds 1 and 2 inhibited the LPS/IFNγ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC50 values of 4.1 µM (±0.2 µM) and 1.0 µM (±0.06 µM) respectively. Moreover, compounds 1 and 2 reduced mRNA levels and synthesis of pro-inflammatory mediators such as cytokines and chemokines in LPS/IFNγ stimulated MonoMac6 cells by interfering with the Stat1 and NFκB pathway.

scholarly journals Estrogen Up-Regulates Hepatic Expression of Suppressors of Cytokine Signaling-2 and -3 in Vivo and in Vitro

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5525-5531 ◽  
Author(s):  
Gary M. Leong ◽  
Sofia Moverare ◽  
Jesena Brce ◽  
Nathan Doyle ◽  
Klara Sjögren ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Hepatoma Cells ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Wild Type ◽  
Hepatic Expression ◽  
Suppressors Of Cytokine Signaling

Abstract Suppressors of cytokine signaling (SOCS) are important negative regulators of cytokine action. We recently reported that estrogen stimulates SOCS-2 expression and inhibits GH signaling in kidney cells. The effects of estrogen on SOCS expression in other tissues are unclear. The aim of this study was to investigate in vivo and in vitro whether estrogen affected SOCS expression in the liver, a major target organ of GH. The in vivo hepatic effects of estrogen on ovariectomized mice lacking estrogen receptor (ER)-α, ERβ, or both and their wild-type littermates were examined by DNA microarray analysis. In vitro, the effects of estrogen on SOCS expression in human hepatoma cells were examined by reverse transcription quantitative PCR. Long-term (3 wk) estrogen treatment induced a 2- to 3-fold increase in hepatic expression of SOCS-2 and -3 in wild-type and ERβ knockout mice but not in those lacking ERα or both ER subtypes. Short-term treatment (at 24 h) increased the mRNA level of SOCS-3 but not SOCS-2. In cultured hepatoma cells, estrogen increased SOCS-2 and -3 mRNA levels by 2-fold in a time- and dose-dependent manner (P < 0.05). Estrogen induced murine SOCS-3 promoter activity by 2-fold (P < 0.05) in constructs containing a region between nucleotides −1862 and −855. Moreover, estrogen and GH had additive effects on the SOCS-3 promoter activity. In summary, estrogen, via ERα, up-regulated hepatic expression of SOCS-2 and -3, probably through transcriptional activation. This indicates a novel mechanism of estrogen regulation of cytokine action.

scholarly journals Anti-Inflammatory Effects of Phenolic Compounds Isolated from Quercus Mongolica Fisch. ex Ledeb. on UVB-Irradiated Human Skin Cells

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3094 ◽  
Author(s):  
Jun Yin ◽  
Han Hyuk Kim ◽  
In Hyeok Hwang ◽  
Dong Hee Kim ◽  
Min Won Lee
Keyword(s):  
Mrna Expression ◽  
Janus Kinase ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Monocyte Chemoattractant Protein 1 ◽  
Quercus Mongolica ◽  
Cytokines And Chemokines ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Uvb Exposure

Quercus mongolica Fisch. ex Ledeb. (QM) has been used as an oriental traditional medicine to relieve hemorrhoids, fever, and enteritis. We screened the inhibitory activities of the extracts and compounds (1–6) isolated from QM on the production of inflammatory cytokines and chemokines to evaluate their anti-inflammatory activities. Further, we evaluated the expression levels of cytokines, chemokines, and immune factors on pedunculagin (PC, 1), which was selected from isolated compounds (1–6) because of its potential anti-inflammation effect. Additionally, we evaluated whether the inflammation mitigation effects of PC (1) following UVB exposure in keratinocytes occurred because of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT)/Janus kinase (JAK) activation. PC (1) remarkably suppressed interleukin (IL)-6, IL-10, IL-13, and monocyte chemoattractant protein-1 (MCP-1) mRNA expression and reduced the mRNA expression level of Cyclooxygenase-2 (COX-2) and also reduced the phosphorylation of p38 mitogen-activated protein kinases (p38), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a concentration-dependent manner.

Evidence that estrogen receptor β enhances MMP-13 promoter activity in HIG-82 cells and that this enhancement can be influenced by ligands and involves specific promoter sites

2007 ◽  
Vol 85 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Ting Lu ◽  
Yamini Achari ◽  
Jerome B. Rattner ◽  
David A. Hart
Keyword(s):  
Estrogen Receptor ◽  
Promoter Activity ◽  
Estrogen Receptor Β ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Connective Tissues ◽  
Matrix Metalloproteinase 13 ◽  
Promoter Construct ◽  
The Impact ◽  
Dose Dependent

Degradation of articular cartilage is characteristic of osteoarthritis, and matrix metalloproteinase-13 (MMP-13) has been implicated in this condition. Estrogen receptors (ERs) are present in connective tissues, indicating these tissues' potential responsiveness to estrogen. We based this study on the hypothesis that estrogen receptor β (ERβ) can modulate MMP-13 promoter activity. Transfection of cells with ERβ constructs led to the induction of the endogenous MMP-13 gene, as evidenced by increased mRNA levels. The results also indicated that MMP-13 promoter construct activity in the HIG-82 cell line significantly increased when ERβ was present, and that estrogen downregulated this response in a dose-dependent manner. ERβ was shown to enhance MMP-13 expression somewhat more strongly than ERα, and the impact of a number of selective ER modulators (tamoxifen, raloxifene, and ICI 182,780) on ERβ enhancement of promoter activity was found to be significantly less than that of estrogen. Furthermore, transcription regulatory sites in the MMP-13 promoter, specifically AP-1 and PEA-3, were shown to act in conjunction to mediate ERβ effects. Thus, ERβ likely influences MMP-13 promoter expression in normal and disease processes.

scholarly journals LPA stimulates intestinal DRA gene transcription via LPA2 receptor, PI3K/AKT, and c-Fos-dependent pathway

2012 ◽  
Vol 302 (6) ◽  
pp. G618-G627 ◽  
Author(s):  
Amika Singla ◽  
Anoop Kumar ◽  
Shubha Priyamvada ◽  
Maliha Tahniyath ◽  
Seema Saksena ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Gene Transcription ◽  
Promoter Activity ◽  
Intestinal Epithelial Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Short Term ◽  
Exchange Activity

DRA (downregulated in adenoma) or SLC26A3 is the major apical anion exchanger mediating Cl− absorption in intestinal epithelial cells. Disturbances in DRA function and expression have been implicated in diarrheal conditions such as congenital chloride diarrhea and inflammatory bowel diseases. Previous studies have shown that DRA is subject to regulation by short-term and transcriptional mechanisms. In this regard, we have recently shown that short-term treatment by lysophosphatidic acid (LPA), an important bioactive phospholipid, stimulates Cl−/HCO3−(OH−) exchange activity via an increase in DRA surface levels in human intestinal epithelial cells. However, the long-term effects of LPA on DRA at the level of gene transcription have not been examined. The present studies were aimed at investigating the effects of LPA on DRA function and expression as well as elucidating the mechanisms underlying its transcriptional regulation. Long-term LPA treatment increased the Cl−/HCO3− exchange activity in Caco-2 cells. LPA treatment (50–100 μM) of Caco-2 cells significantly stimulated DRA mRNA levels and DRA promoter activity (−1183/+114). This increase in DRA promoter activity involved the LPA2 receptor and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. Progressive deletions from −1183/+114 to −790/+114 abrogated the stimulatory effects of LPA, indicating that the −1183/−790 promoter region harbors LPA response elements. Utilizing EMSA and mutational studies, our results showed that LPA induced the DRA promoter activity in a c-Fos-dependent manner. LPA also increased the protein expression of c-Fos and c-Jun in Caco-2 cells. Furthermore, overexpression of c-Fos but not c-Jun enhanced the DRA promoter activity. This increase in DRA transcription in response to LPA indicates that LPA may act as an antidiarrheal agent and could be exploited for the treatment of diarrhea associated with inflammatory or infectious diseases of the gut.

scholarly journals Synergistic Up-Regulation of Vascular Endothelial Growth Factor (VEGF) Expression in Macrophages by Adenosine A2AReceptor Agonists and Endotoxin Involves Transcriptional Regulation via the Hypoxia Response Element in the VEGF Promoter

2007 ◽  
Vol 18 (1) ◽  
pp. 14-23 ◽  
Author(s):  
Madhuri Ramanathan ◽  
Grace Pinhal-Enfield ◽  
Irene Hao ◽  
Samuel Joseph Leibovich
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Transcriptional Regulation ◽  
Growth Factor ◽  
Promoter Activity ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

Macrophages are an important source of vascular endothelial growth factor (VEGF). Adenosine A2Areceptor (A2AR) agonists with Toll-like receptor (TLR) 2, 4, 7, and 9 agonists synergistically induce macrophage VEGF expression. We show here using VEGF promoter-luciferase reporter constructs that the TLR4 agonist Escherichia coli lipopolysaccharide (LPS) and the A2AR agonists NECA and CGS21680 synergistically augment VEGF transcription in macrophages and that the HRE in the VEGF promoter is essential for this transcription. We examined whether LPS and/or NECA induce HIF-1α expression. HIF-1α mRNA levels were increased in LPS-treated macrophages in an NF-κB–dependent manner; NECA strongly increased these levels in an A2AR-dependent manner. LPS induced luciferase expression from a HIF-1α promoter-luciferase construct in an A2AR-independent manner. Further stimulation with NECA did not increase HIF-1α promoter activity, indicating that the A2AR-dependent increase in HIF-1α mRNA is post-transcriptional. LPS/NECA treatment also increased HIF-1α protein and DNA binding levels. Deletion of putative NF-κB–binding sites from the VEGF promoter did not affect LPS/NECA-induced VEGF promoter activity, suggesting that NF-κB is not directly involved in VEGF transcription. Taken together, these data indicate that LPS/NECA-induced VEGF expression involves transcriptional regulation of the VEGF promoter by HIF-1α through the HRE. HIF-1α is transcriptionally induced by LPS and post-transcriptionally up-regulated in an A2AR-dependent manner.

scholarly journals Insulin-Attenuated Inflammatory Response of Dendritic Cells in Diabetes by Regulating RAGE-PKCβ1-IRS1-NF-κB Signal Pathway: A Study on the Anti-Inflammatory Mechanism of Insulin in Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Liding Zhao ◽  
Ya Li ◽  
Qingbo Lv ◽  
Min Wang ◽  
Yi Luan ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Response ◽  
Neutralizing Antibody ◽  
Serine Phosphorylation ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Mice Model ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory ◽  
Immune Maturation

Background. Diabetes is associated with chronic inflammation, and dendritic cells (DCs) have proinflammatory effect in diabetes. The anti-inflammatory effect of insulin on diabetes is not entirely clear. The study aims to examine insulin-induced effects on the inflammatory response in DCs. Methods. Twenty-one C57BL/6 mice were divided into 3 groups. Streptozotocin was injected into the diabetic mice model. The bone marrow-derived DCs (BMDCs) were obtained from C57BL/6 mice. CD83, CD86, and type II major histocompatibility complex (MHC-II) of BMDCs were measured by flow cytometry. The fluctuations in the RNA levels of cytokines and chemokines were analyzed by quantitative RT-PCR. The concentrations of IFN-γ and TNF-α were calculated using ELISA kits, and the proteins were detected using western blot. Results. In CD11c+ DCs derived from the spleens with hyperglycemia, the expression of CD83 and CD86 in diabetic mice was significantly upregulated, coupled with a higher secretion level of cytokines and chemokines, and increased phosphorylation of NF-κB and IκB. Insulin therapy was found to have a reversal effect on the inflammatory response and immune maturation in DCs. In AGEs-BSA-stimulated BMDCs, insulin repressed the immune maturation and downregulated the expression of RAGE, phospho-PKCβ1, and serine phospho-IRS1 in an adose-dependent manner. Such effects can be abolished by PMA, but not IR-neutralizing antibody. AGEs-BSA-induced BMDCs immune maturation was inhibited by the neutralizing antibody of RAGE, the PKCβ1 inhibitor, or the IRS1 siRNA. Conclusions. Insulin has the capability of attenuating the inflammatory response of DCs in diabetes, partly through the downregulation of RAGE expression followed by the inhibition of PKCβ1 phosphorylation and IRS1 serine phosphorylation, resulting in the inactivation of IR binding-independent NF-κB. This might partly explain the antiatherogenic effect of insulin on diabetes.

scholarly journals Allium porrum Extract Decreases Effector Cell Degranulation and Modulates Airway Epithelial Cell Function

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1303 ◽  
Author(s):  
Sara Benedé ◽  
Ana Gradillas ◽  
Mayte Villalba ◽  
Eva Batanero
Keyword(s):  
Cell Function ◽  
Total Phenolic ◽  
Allium Porrum ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Allergy Treatment ◽  
Lower Permeability ◽  
Anti Inflammatory ◽  
High Concentrations

Allium genus plants, such as leek (Allium porrum), are rich sources of anti-inflammatory and anti-oxidant secondary metabolites; this is of interest because it demonstrates their suitability as pharmacological alternatives for inflammatory processes, including allergy treatment. The composition of methanolic leek extract (LE) was analyzed by GC–MS and LC–IT/MS, and the total phenolic content and antioxidant capacity were quantified by colorimetric methods. Its pharmacological potential was analyzed in human bronchial epithelial Calu-3 cells, human mast cells LAD2, and humanized rat basophiles RBL-2H3. LE exhibited a cytotoxic effect on Calu-3 cells and HumRBL-2H3 cells only at high concentrations and in a dose-dependent manner. Moreover, LE decreased the degranulation of LAD2 and HumRBL-2H3 cells. LE treatment also significantly prevented alterations in transepithelial electrical resistance values and mRNA levels of glutathione-S-transferase (GST), c-Jun, and NFκB after treatment with H2O2 in ALI-cultured Calu-3 cells. Finally, ALI-cultured Calu-3 cells treated with LE showed lower permeability to Ole e 1 compared to untreated cells. A reduction in IL-6 secretion in ALI-cultured Calu-3 cells treated with LE was also observed. In summary, the results obtained in this work suggest that A. porrum extract may have potential anti-allergic effects due to its antioxidant and anti-inflammatory properties. This study provides several important insights into how LE can protect against allergy.

scholarly journals SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

2013 ◽  
Vol 9 ◽  
pp. 2866-2876 ◽  
Author(s):  
Silke Felix ◽  
Louis P Sandjo ◽  
Till Opatz ◽  
Gerhard Erkel
Keyword(s):  
Sesquiterpene Lactone ◽  
Promoter Activity ◽  
Survivin Expression ◽  
Anticancer Therapy ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Survivin Promoter ◽  
Apoptosis Gene ◽  
Apoptosis Regulation ◽  
Dose Dependent

Survivin, a member of the IAP (inhibitor of apoptosis) gene family, is overexpressed in virtually all human cancers and is functionally involved in the inhibition of apoptosis, regulation of cell proliferation, metastasis and resistance to therapy. Because of its upregulation in malignancy, survivin has currently attracting considerable interest as a new target for anticancer therapy. In a screening of approximately 200 strains of imperfect fungi for the production of inhibitors of survivin promoter activity, a new drimane sesquiterpene lactone, SF002-96-1, was isolated from fermentations of an Aspergillus species. The compound inhibited survivin promoter activity in transiently transfected Colo 320 cells in a dose dependent manner with IC50 values of 3.42 µM (1.3 µg/mL). Moreover, it also reduced mRNA levels and protein synthesis of survivin and triggered apoptosis.

scholarly journals Quercetin Inhibits Inflammatory Response Induced by LPS from Porphyromonas gingivalis in Human Gingival Fibroblasts via Suppressing NF-κB Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Gang Xiong ◽  
Wansheng Ji ◽  
Fei Wang ◽  
Fengxiang Zhang ◽  
Peng Xue ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Interleukin 1 ◽  
Human Gingival Fibroblasts ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Peroxisome Proliferator Activated Receptor ◽  
Anti Inflammatory

Quercetin, a natural flavonol existing in many food resources, has been reported to be an effective antimicrobial and anti-inflammatory agent for restricting the inflammation in periodontitis. In this study, we aimed to investigate the anti-inflammatory effects of quercetin on Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide- (LPS-) stimulated human gingival fibroblasts (HGFs). HGFs were pretreated with quercetin prior to LPS stimulation. Cell viability was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), along with chemokine interleukin-8 (IL-8), were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IκBα, p65 subunit of nuclear factor-kappa B (NF-κB), peroxisome proliferator-activated receptor-γ (PPAR-γ), liver X receptor α (LXRα), and Toll-like receptor 4 (TLR4) were measured by real-time quantitative PCR (RT-qPCR). The protein levels of IκBα, p-IκBα, p65, p-p65, PPAR-γ, LXRα, and TLR4 were characterized by Western blotting. Our results demonstrated that quercetin inhibited the LPS-induced production of IL-1β, IL-6, IL-8, and TNF-α in a dose-dependent manner. It also suppressed LPS-induced NF-κB activation mediated by TLR4. Moreover, the anti-inflammatory effects of quercetin were reversed by the PPAR-γ antagonist of GW9662. In conclusion, these results suggested that quercetin attenuated the production of IL-1β, IL-6, IL-8, and TNF-α in P. gingivalis LPS-treated HGFs by activating PPAR-γ which subsequently suppressed the activation of NF-κB.

scholarly journals Chlorogenic Acid Potentiates the Anti-Inflammatory Activity of Curcumin in LPS-Stimulated THP-1 Cells

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2706 ◽  
Author(s):  
Akshay Bisht ◽  
Martin Dickens ◽  
Kay Rutherfurd-Markwick ◽  
Rohith Thota ◽  
Anthony N. Mutukumira ◽  
...  
Keyword(s):  
Cell Viability ◽  
Chlorogenic Acid ◽  
Mrna Expression ◽  
Inflammatory Marker ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Dependent Manner ◽  
Major Barrier ◽  
Tnf Α ◽  
Anti Inflammatory

The anti-inflammatory effects of curcumin are well documented. However, the bioavailability of curcumin is a major barrier to its biological efficacy. Low-dose combination of complimentary bioactives appears to be an attractive strategy for limiting barriers to efficacy of bioactive compounds. In this study, the anti-inflammatory potential of curcumin in combination with chlorogenic acid (CGA), was investigated using human THP-1 macrophages stimulated with lipopolysaccharide (LPS). Curcumin alone suppressed TNF-α production in a dose-dependent manner with a decrease in cell viability at higher doses. Although treatment with CGA alone had no effect on TNF-α production, it however enhanced cell viability and co-administration with curcumin at a 1:1 ratio caused a synergistic reduction in TNF-α production with no impact on cell viability. Furthermore, an qRT-PCR analysis of NF-κB pathway components and inflammatory biomarkers indicated that CGA alone was not effective in reducing the mRNA expression of any of the tested inflammatory marker genes, except TLR-4. However, co-administration of CGA with curcumin, potentiated the anti-inflammatory effects of curcumin. Curcumin and CGA together reduced the mRNA expression of pro-inflammatory cytokines [TNF-α (~88%) and IL-6 (~99%)], and COX-2 (~92%), possibly by suppression of NF-κB (~78%), IκB-β-kinase (~60%) and TLR-4 receptor (~72%) at the mRNA level. Overall, co-administration with CGA improved the inflammation-lowering effects of curcumin in THP-1 cells.

Sign in / Sign up

Export Citation Format

Share Document