scholarly journals Allicin Alleviates Dextran Sodium Sulfate- (DSS-) Induced Ulcerative Colitis in BALB/c Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Ashok Kumar Pandurangan ◽  
Salmiah Ismail ◽  
Zeinab Saadatdoust ◽  
Norhaizan Mohd. Esa
Keyword(s):  
Body Weight ◽  
Proinflammatory Cytokines ◽  
Sodium Sulfate ◽  
Nuclear Translocation ◽  
Dextran Sodium Sulfate ◽  
Nuclear Accumulation ◽  
Mrna Levels ◽  
Inhibitory Protein ◽  
Reduced Body ◽  
Enzymic Antioxidants

The objective of this study is to evaluate the effect of allicin (10 mg/kg body weight, orally) in an experimental murine model of UC by administering 2.5% dextran sodium sulfate (DSS) in drinking water to BALB/c mice. DSS-induced mice presented reduced body weight, which was improved by allicin administration. We noted increases in CD68 expression, myeloperoxidase (MPO) activities, and Malonaldehyde (MDA) and mRNA levels of proinflammatory cytokines, such astumor necrosis factor- (TNF-)α, interleukin- (IL-) 1β, IL-6, andIL-17, and decrease in the activities of enzymic antioxidants such as superoxide dismutase (SOD), Catalase (CAT), Glutathione reductase (GR), and Glutathione peroxidase (GPx) in DSS-induced mice. However, allicin treatment significantly decreased CD68, MPO, MDA, and proinflammatory cytokines and increased the enzymic antioxidants significantly (P<0.05). In addition, allicin was capable of reducing the activation and nuclear accumulation of signal transducer and activator of transcription 3 (STAT3), thereby preventing degradation of the inhibitory protein IκB and inducing inhibition of the nuclear translocation of nuclear factor (NF)-κB-p65 in the colonic mucosa. These findings suggest that allicin exerts clinically useful anti-inflammatory effects mediated through the suppression of the NF-κB and IL-6/p-STAT3Y705pathways.

scholarly journals Salicylates Ameliorate Intestinal Inflammation by Activating Macrophage AMPK

2020 ◽  
Author(s):  
Suhrid Banskota ◽  
Huaqing Wang ◽  
Yun Han Kwon ◽  
Jaya Gautam ◽  
Pallavi Gurung ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Nuclear Translocation ◽  
Dextran Sodium Sulfate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aminosalicylic Acid ◽  
Inflammatory Conditions ◽  
Inflammatory Bowel

Abstract Background Inflammatory bowel diseases are the most common chronic intestinal inflammatory conditions, and their incidence has shown a dramatic increase in recent decades. Limited efficacy and questionable safety profiles with existing therapies suggest the need for better targeting of therapeutic strategies. Adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of cellular metabolism and has been implicated in intestinal inflammation. Macrophages execute an important role in the generation of intestinal inflammation. Impaired AMPK in macrophages has been shown to be associated with higher production of proinflammatory cytokines; however, the role of macrophage AMPK in intestinal inflammation and the mechanism by which it regulates inflammation remain to be determined. In this study, we investigated the role of AMPK with a specific focus on macrophages in the pathogenesis of intestinal inflammation. Methods A dextran sodium sulfate-induced colitis model was used to assess the disease activity index, histological scores, macroscopic scores, and myeloperoxidase level. Proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β were measured by enzyme-linked immunosorbent assay. Transient transfection of AMPKβ1 and LC3-II siRNA in RAW 264.7 cells was performed to elucidate the regulation of autophagy by AMPK. The expression of p-AMPK, AMPK, and autophagy markers (eg, LC3-II, p62, Beclin-1, and Atg-12) was analyzed by Western blot. Results Genetic deletion of AMPKβ1 in macrophages upregulated the production of proinflammatory cytokines, aggravated the severity of dextran sodium sulfate-induced colitis in mice, which was associated with an increased nuclear translocation of nuclear factor-κB, and impaired autophagy both in vitro and in vivo. Notably, the commonly used anti-inflammatory 5-aminosalicylic acid (ie, mesalazine) and sodium salicylate ameliorated dextran sodium sulfate-induced colitis through the activation of macrophage AMPK targeting the β1 subunit. Conclusions Together, these data suggest that the development of therapeutic agents targeting AMPKβ1 may be effective in the treatment of intestinal inflammatory conditions including inflammatory bowel disease.

scholarly journals The effect of algal polysaccharides laminarin and fucoidan on colonic pathology, cytokine gene expression and Enterobacteriaceae in a dextran sodium sulfate-challenged porcine model

2016 ◽  
Vol 5 ◽  
Author(s):  
C. J. O'Shea ◽  
J. V. O'Doherty ◽  
J. J. Callanan ◽  
D. Doyle ◽  
K. Thornton ◽  
...  
Keyword(s):  
Body Weight ◽  
Sodium Sulfate ◽  
Basal Diet ◽  
Proximal Colon ◽  
Dextran Sodium Sulfate ◽  
Mrna Abundance ◽  
Cytokine Gene Expression ◽  
Distilled Water ◽  
The Impact ◽  
Algal Polysaccharides

AbstractThe algal polysaccharides laminarin (LAM) and fucoidan (FUC) have potent anti-inflammatory activities in the gastrointestinal tract. Our objective was to examine the impact of prior consumption of LAM and/or FUC on pathology and inflammation following a dextran sodium sulfate (DSS) challenge in pigs. Pigs (n 7/group) were assigned to one of five experimental groups for 56 d. From 49–55 d, distilled water or DSS was administered intragastrically. The experimental groups were: (1) basal diet + distilled water (control); (2) basal diet + DSS (DSS); (3) basal diet + FUC + DSS (FUC + DSS); (4) basal diet + LAM + DSS (LAM + DSS); and (5) basal diet + LAM + FUC + DSS (LAMFUC + DSS). The DSS group had decreased body-weight gain (P < 0·05) and serum xylose (P < 0·05), and increased proximal colon pathology score (P < 0·05), diarrhoeal score (P < 0·001) and colonic Enterobacteriaceae (P < 0·05) relative to the control group. The FUC + DSS (P < 0·01), LAM + DSS (P < 0·05) and LAMFUC + DSS (P < 0·05) groups had improved diarrhoeal score, and the LAMFUC + DSS (P < 0·05) group had improved body weight relative to the DSS group. The FUC + DSS group (P < 0·001), LAM + DSS group (P < 0·05) and LAMFUC + DSS group (P < 0·001) had lower IL-6 mRNA abundance relative to the DSS group. The LAM + DSS group had reduced Enterobacteriaceae in proximal colon digesta relative to the DSS group (P < 0·05). In conclusion, FUC or a combination of FUC and LAM improved body-weight loss, diarrhoeal scores and clinical variables associated with a DSS challenge in pigs, in tandem with a reduction in colonic IL-6 mRNA abundance.

scholarly journals PPARα Agonist Suppresses Inflammation after Corneal Alkali Burn by Suppressing Proinflammatory Cytokines, MCP-1, and Nuclear Translocation of NF-κB

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 114 ◽  
Author(s):  
Yuichiro Nakano ◽  
Masaaki Uchiyama ◽  
Takeshi Arima ◽  
Shinya Nagasaka ◽  
Tsutomu Igarashi ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Nuclear Translocation ◽  
Vehicle Group ◽  
Peroxisome Proliferator ◽  
Corneal Tissue ◽  
Mrna Levels ◽  
Basal Cells ◽  
Monocyte Chemoattractant Protein 1 ◽  
Corneal Injury ◽  
Pparα Agonist

We investigated the effect of a peroxisome proliferator-activated receptor α (PPARα) agonist after corneal alkali injury. Fenofibrate 0.05% (PPARα agonist group) or vehicle (Vehicle group) was topically instilled onto the rat cornea after injury. Histological, immunohistochemical, and real-time reverse transcription PCR analyses were performed. PPARα-positive cells were observed among basal cells of the corneal epithelium in normal and alkali-burned corneas. The number of infiltrating neutrophils and macrophages at the corneal limbus was lower in the PPARα agonist group. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor-An mRNA expression was suppressed in the PPARα agonist group compared to the Vehicle group. mRNA levels of nuclear factor kappa B (NF-κB) in corneal tissue were not different. However, NF-κB was expressed in the cytoplasm of basal cells in the PPARα agonist group and in the nucleus in the Vehicle group. MCP-1 was more weakly expressed in the PPARα agonist group. The PPARα agonist inhibited inflammation during the early phase after injury. Anti-inflammatory effects of the PPARα agonist included prevention of up-regulation of proinflammatory cytokines and MCP-1, and prevention of inflammatory cell infiltration into the injured cornea. Thus, a PPARα agonist may be a promising treatment for corneal injury.

scholarly journals Dietary pterostilbene supplementation attenuates intestinal damage and immunological stress of broiler chickens challenged with lipopolysaccharide

2019 ◽  
Vol 98 (1) ◽  
Author(s):  
Hao Zhang ◽  
Yanan Chen ◽  
Yueping Chen ◽  
Yue Li ◽  
Peilu Jia ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Nuclear Translocation ◽  
Receptor Protein ◽  
Nuclear Accumulation ◽  
Broiler Chicks ◽  
Intestinal Damage ◽  
Mrna Levels ◽  
Lps Challenge ◽  
Junction Protein ◽  
Immunological Stress

Abstract The present study explored the potential effect of pterostilbene as a prophylactic treatment on the lipopolysaccharide (LPS)-induced intestinal injury of broiler chickens by monitoring changes in mucosal injury indicators, redox status, and inflammatory responses. In total, 192 one-day-old male Ross 308 broiler chicks were randomly divided into four groups. This trial consisted of a 2 × 2 factorial design with a diet factor (supplemented with 0 or 400 mg/kg pterostilbene from 1 to 22 d of age) and a stress factor (intraperitoneally injected with saline or LPS at 5.0 mg/kg BW at 21 da of age). The results showed that LPS challenge induced a decrease in BW gain (P &lt; 0.001) of broilers during a 24-h period postinjection; however, this decrease was prevented by pterostilbene supplementation (P = 0.031). Administration of LPS impaired the intestinal integrity of broilers, as indicated by increased plasma diamine oxidase (DAO) activity (P = 0.014) and d-lactate content (P &lt; 0.001), reduced jejunal villus height (VH; P &lt; 0.001) and the ratio of VH to crypt depth (VH:CD; P &lt; 0.001), as well as a decreased mRNA level of jejunal tight junction protein 1 (ZO-1; P = 0.002). In contrast, pterostilbene treatment increased VH:CD (P = 0.018) and upregulated the mRNA levels of ZO-1 (P = 0.031) and occludin (P = 0.024) in the jejunum. Consistently, pterostilbene counteracted the LPS-induced increased DAO activity (P = 0.011) in the plasma. In addition, the LPS-challenged broilers exhibited increases in nuclear accumulation of nuclear factor kappa B (NF-κB) p65 (P &lt; 0.001), the protein content of tumor necrosis factor α (P = 0.033), and the mRNA abundance of IL-1β (P = 0.042) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3; P = 0.019). In contrast, pterostilbene inhibited the nuclear translocation of NF-κB p65 (P = 0.039) and suppressed the mRNA expression of IL-1β (P = 0.003) and NLRP3 (P = 0.049) in the jejunum. Moreover, pterostilbene administration induced a greater amount of reduced glutathione (P = 0.017) but a lower content of malondialdehyde (P = 0.023) in the jejunum of broilers compared with those received a basal diet. Overall, the current study indicates that dietary supplementation with pterostilbene may play a beneficial role in alleviating the intestinal damage of broiler chicks under the conditions of immunological stress.

scholarly journals Antiobesity Effects of the β-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5855-5864 ◽  
Author(s):  
Jonathan D. Roth ◽  
Heather Hughes ◽  
Eric Kendall ◽  
Alain D. Baron ◽  
Christen M. Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Respiratory Quotient ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Lean Tissue ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Cell Hormone

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 μg/kg·d, 22d) reduced food intake and slowed weight gain: approximately 10% (P &lt; 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P &lt; 0.05). Whereas PF decreased lean tissue (P &lt; 0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean ± se, 0.82 ± 0.0, 0.81 ± 0.0, respectively; P &lt; 0.05) similar to VEH (0.84 ± 0.01). Energy expenditure (EE mean ± se) tended to be reduced by PF (5.67 ± 0.1 kcal/h·kg) and maintained by amylin (5.86 ± 0.1 kcal/h·kg) relative to VEH (5.77 ± 0.0 kcal/h·kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74 ± 0.09 kcal/·kg; P &lt; 0.05) relative to VEH (5.49 ± 0.06) and PF (5.38 ± 0.07 kcal/h·kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P &lt; 0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P &lt; 0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.

scholarly journals Signaling Events Involved in Macrophage Chemokine Expression in Response to Monosodium Urate Crystals

2004 ◽  
Vol 279 (50) ◽  
pp. 52797-52805 ◽  
Author(s):  
Maritza Jaramillo ◽  
Marianne Godbout ◽  
Paul H. Naccache ◽  
Martin Olivier
Keyword(s):  
Nuclear Translocation ◽  
Gouty Arthritis ◽  
Acute Gout ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Monosodium Urate ◽  
Inhibitory Protein ◽  
Concentration Dependent Manner ◽  
Chemokine Production ◽  
Msu Crystals

Chemokine production has been associated with leukocyte infiltration into the joint during gouty arthritis, and monosodium urate (MSU) crystals, the causative agent of this arthropathy, have been shown to modulate their expression. In the present study, we investigated the transductional mechanisms underlying this cellular regulation in the murine macrophage cell line B10R. We report that MSU crystals rapidly and transiently increase mRNA levels of various chemokines in a concentration-dependent manner. Examination of second messenger activation revealed that macrophage exposure to MSU crystals led to MEK1/2, ERK1/2, and inhibitory protein κBα phosphorylation as well as to NF-κB and AP-1 nuclear translocation. Of interest, specific blockage of the ERK1/2 pathway drastically reduced up-modulation of MSU crystal-mediated chemokine production and activation of nuclear factors. Similarly, selective inhibition of NF-κB suppressed NF-κB DNA binding activity and the induction of all chemokine transcripts. These findings indicate that ERK1/2-dependent signals seem to be required for AP-1 and NF-κB activation and subsequent mRNA expression of the various macrophage chemokines. In addition, transcription and stability assays performed in presence of actinomycin D showed that MSU crystal-mediated MIP-1β mRNA up-regulation resulted solely from transcriptional control, whereas that of MIP-1α, MIP-2, and MCP-1 was due to both gene transcription activation and mRNA posttranscriptional stabilization. Overall, the results of this study help to define the molecular events that govern macrophage chemokine regulation in response to MSU crystals, which is of paramount importance to better understand, and eventually to tame, the inflammatory response during acute gout.

scholarly journals miR-135a Protects Dextran Sodium Sulfate-Induced Inflammation in Human Colorectal Cell Lines by Activating STAT3 Signal

2018 ◽  
Vol 51 (3) ◽  
pp. 1001-1012 ◽  
Author(s):  
Jingru Zhang ◽  
Bo Lian ◽  
Yan Shang ◽  
Chun Li ◽  
Qingkai Meng
Keyword(s):  
Proinflammatory Cytokines ◽  
Sodium Sulfate ◽  
Inflammatory Responses ◽  
Dextran Sodium Sulfate ◽  
Stat3 Phosphorylation ◽  
Colorectal Cell ◽  
Anti Inflammatory ◽  
Colonic Cells ◽  
Ht 29 ◽  
Inflammatory Effect

Background/Aims: miR-135a is reduced in several cancers and has been suggested to mediate immune and inflammatory responses. However, the effect of miR-135a on inflammatory bowel diseases was obscure. This study firstly attempted to investigate the hypothesis that miR-135a alleviates dextran sodium sulfate (DSS)-induced inflammation in colonic cells and potential mechanisms are also studied. Methods: Caco-2 and HT-29 cells in this study were treated with DSS, miR-135a mimic, and S3I-201, and then CKK-8 assay was used to test cell viability. Expressions of miR-135a, cytokines, and signal transducers and activators of transcription factors (STATs) were determined by RT-PCR. Also, cytokine productions were further tested by using ELISA kits. Activation or inactivation of STAT3 signal was validated by western blotting analysis. Results: The results showed that DSS markedly downregulated miR-135a expression (P< 0.05) and induced inflammatory response in Caco-2 and HT-29 cells evidenced by the up regulations and productions of interleukin-1β (IL-1β) and tumor necrosis factor-ɑ (TNF-ɑ) (P< 0.05). Transfection with miR-135a mimic significantly alleviated DSS-induced upregulation and productions of IL-1β and TNF-ɑ in Caco-2 and HT-29 cells (P< 0.05). STATs were analyzed and miR-135a mimic treatment reversed STAT3 downregulation in DSS-challenged Caco-2 and HT-29 cells compared with the mimic control (P< 0.05). Also, STAT3 phosphorylation was inhibited in DSS-challenged Caco-2 cells and miR-135a mimic activated STAT3 signal (P< 0.05). S3I-201, an inhibitor of STAT3 signal, further used to inactivate STAT3 signal and the results showed that S3I-201 blocked the anti-inflammatory effect of miR-135a mimic on Caco-2 and HT-29 cells evidenced by the lowered expressions and productions of proinflammatory cytokines ((IL-1β and TNF-ɑ) (P< 0.05). Conclusion: Our results indicated that miR-135a alleviated DSS-induced inflammation and activated STAT3 signal in colonic cells. Inhibition of STAT3 reversed the anti-inflammatory function of miR-135a by regulating proinflammatory cytokines. Thus, STAT3 signal might serve, at least in part, as the potential mechanism of miR-135a-mediated anti-inflammatory effect in colonic cells.

scholarly journals Different Mechanism and Efficacy of Dextran-Sodium Sulfate and 2,4,6-Trinitrobenzene Sulphonic Acid in Modeling Ulcerative Colitis in C57BL/6 Mice

2021 ◽  
Author(s):  
Qiaobo YE ◽  
Zhen YE ◽  
Mingquan WU ◽  
Kaihua QIN ◽  
Fating LU ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Chronic Ulcerative Colitis ◽  
Sodium Sulfate ◽  
Activity Index ◽  
Disease Activity Index ◽  
Dextran Sodium Sulfate ◽  
Sulphonic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Trinitrobenzene Sulphonic Acid

Abstract Background and Aims: Dextran-sodium sulfate and 2,4,6-trinitrobenzene sulphonic acid are common modeling methods in studying ulcerative colitis. Little attention has been paid to the mechanism differences between the two approaches. Here, we aim to compare the mechanisms and efficacy of these two models and wish to provide fundamental proves for choosing ideal ulcerative colitis models. Methods: Dextran-sodium sulfate and 2,4,6-trinitrobenzene sulphonic acid were applied to induce the colitis in C57BL/6 mice for seven days. Body weight and disease activity index were assessed. Hematology was detected by routine blood test. Histopathology was analyzed by hematoxylin-eosin staining section. Enzyme-linked immunosorbent assay, Western blot and quantitative real-time PCR were used to detect the cytokines protein levels and mRNA levels. Flow cytometry were used to detect the cycles and subsets of splenic cells. Results: Dextran-sodium sulfate induced colitis in C57BL/6 mice showed higher acute immune activities, while 2,4,6-trinitrobenzene sulphonic acid induced colitis showed chronic immune activities with high platelet amounts and activation. Dextran-sodium sulfate is more suitable for modeling acute ulcerative colitis. On the contrary, 2,4,6-trinitrobenzene sulphonic acid is more appropriate for modeling chronic ulcerative colitis. Conclusions: Dextran-sodium sulfate treatment within 7 days in C57BL/6 mice is a suitable experimental model for studying human acute ulcerative colitis with immune response, fecal blood and acute pathogenic damage. Conversely, 2,4,6-trinitrobenzene sulphonic acid treatment within 7 days is more appropriate for studying human chronic ulcerative colitis with hypercoagulable state, IL-2 over-expression state and chronic pathogenic damage.

scholarly journals Enzyme-Treated Asparagus Extract Prevents Hydrogen Peroxide-Induced Pro-Inflammatory Responses by Suppressing p65 Nuclear Translocation in Skin L929 Fibroblasts

2016 ◽  
Vol 11 (12) ◽  
pp. 1934578X1601101 ◽  
Author(s):  
Ken Shirato ◽  
Jun Takanari ◽  
Takuya Sakurai ◽  
Junetsu Ogasawara ◽  
Kazuhiko Imaizumi ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Skin Fibroblasts ◽  
Nuclear Accumulation ◽  
Inos Mrna ◽  
Mrna Levels ◽  
Aging Effects ◽  
L929 Cells

We recently reported that enzyme-treated asparagus extract (ETAS) attenuates hydrogen peroxide (H2O2)-stimulated matrix metalloproteinase-9 expression in skin fibroblast L929 cells. To further elucidate the anti-aging effects of ETAS on skin, we examined whether ETAS has preventive effects on H2O2-induced pro-inflammatory responses of skin fibroblasts. H2O2 induced Ser536 phosphorylation and nuclear accumulation of nuclear factor-κB (NF-κB) p65, and increased the mRNA levels of interleukin-12α (IL-12α) and inducible nitric oxide synthase (iNOS) in L929 cells. Pretreatment of the cells with JSH-23, an inhibitor of NF-κB nuclear translocation, abolished the H2O2-induced expression of IL-12α and iNOS, indicating that the increased transcription is regulated by p65. The H2O2-stimulated nuclear accumulation of p65 and induction of IL-12α and iNOS mRNA were significantly attenuated after pretreatment with ETAS for 3 h, and these responses were completely abolished when the duration was extended to 24 h. However, ETAS did not affect the H2O2-stimulated degradation of IκBα and phosphorylation of p65. On the other hand, ETAS treatment for 24 h resulted in decreased protein levels of importin-α. These results suggest that ETAS prevents pro-inflammatory responses by suppressing the p65 nuclear translocation in skin fibroblasts induced by H2O2.

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