Cardiotrophin-1 attenuates experimental colitis in mice

2018 ◽  
Vol 132 (9) ◽  
pp. 985-1001 ◽  
Author(s):  
Vanessa Prieto-Vicente ◽  
Ana I. Sánchez-Garrido ◽  
Víctor Blanco-Gozalo ◽  
Miguel Arévalo ◽  
Enrique García-Sánchez ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Bacterial Translocation ◽  
Caspase 3 ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Nuclear Factor Κb ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Ulcerative Lesions

Cardiotrophin-1 (CT-1) holds potent anti-inflammatory, cytoprotective, and anti-apoptotic effects in the liver, kidneys, and heart. In the present study, the role of endogenous CT-1 and the effect of exogenous CT-1 were evaluated in experimental ulcerative colitis. Colitis was induced in CT-1 knockout and wild-type (WT) mice by administration of dextran sulphate sodium (DSS) in the drinking water during 7 days. CT-1 knockout mice showed higher colon damage and disease severity than WT mice. In addition, CT-1 (200 µg/kg/day, iv) or vehicle (as control) was administered during 3 days to WT, colitic mice, starting on day 4 after initiation of DSS. Disease activity index (DAI), inflammatory markers (tumor necrosis factor α (TNF-α), INFγ, IL-17, IL-10, inducible nitric oxide synthase (iNOS)), colon damage, apoptosis (cleaved caspase 3), nuclear factor κB (NFκB) and STAT-3 activation, and bacterial translocation were measured. Compared with mice treated with DSS, mice also treated with exogenous CT-1 showed lower colon damage, DAI, plasma levels of TNFα, colon expression of TNF-α, INFγ, IL-17, iNOS and cleaved caspase 3, higher NFκB and signal transducer and activator of transcription 3 (STAT3) pathways activation, and absence of bacterial translocation. We conclude that endogenous CT-1 plays a role in the defense and repair response of the colon against ulcerative lesions through an anti-inflammatory and anti-apoptotic effect. Supplementation with exogenous CT-1 ameliorates disease symptoms, which opens a potentially new therapeutic strategy for ulcerative colitis.

scholarly journals Preventive Effect of Cardiotrophin-1 Administration before DSS-Induced Ulcerative Colitis in Mice

2019 ◽  
Vol 8 (12) ◽  
pp. 2086 ◽  
Author(s):  
Ana I. Sánchez-Garrido ◽  
Vanessa Prieto-Vicente ◽  
Víctor Blanco-Gozalo ◽  
Miguel Arévalo ◽  
Yaremi Quiros ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Course ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Tnf Α ◽  
Current Therapies ◽  
Ifn Γ ◽  
Histology And Immunohistochemistry

Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.

scholarly journals Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zengjie Zheng ◽  
Hailong Jiang ◽  
Yan Huang ◽  
Jie Wang ◽  
Lei Qiu ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Activity Index ◽  
Tumor Necrosis Factor Receptor ◽  
Disease Activity Index ◽  
Acute Colitis ◽  
Surface Plasmon Resonance Analysis ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases.

scholarly journals Study on the mechanism of Indigo naturalis and its two main compounds (indigo and indirubin) in the treatment of ulcerative colitis based on TLR4/MyD88/NF-κB pathway and intestinal microorganisms

2020 ◽  
Author(s):  
Qi-yue Yang ◽  
Ya-nan He ◽  
Le-le Ma ◽  
Run-chun Xu ◽  
Nan Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Pathological Section ◽  
Inflammatory Cytokine Production ◽  
Tnf Α ◽  
Indigo Naturalis ◽  
Inflammation Cytokines

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB，TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.

Gisekia pharnaceoides restores colonic mucosal homeostasis by regulating antioxidant enzyme system and cytokines signaling in ulcerative colitis mice model

2021 ◽  
Vol 21 ◽  
Author(s):  
Faraza Javed ◽  
Naveed Aslam ◽  
Hafiza Maida Arshad ◽  
Ambreen Mehmood Awan ◽  
Wafa Majeed ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Hplc Analysis ◽  
Activity Index ◽  
Hematological Parameters ◽  
Disease Activity Index ◽  
Lipid Peroxides ◽  
Mucosal Homeostasis ◽  
Anti Inflammatory

Background: Gisekia pharnaceoides Linn. (Aizoaceae), traditionally known as baluka saag or sareli is commonly found in the deep Cholistan region of Pakistan. It is used by native community for the mitigation of a range of diseases, including inflammatory disorders and gastric ulcers. Objective: This study is designed to evaluate the defensive impact of G. pharnaceoides in acetic acid-induced ulcerative colitis in mice and to discover the mechanism for anti-inflammatory action. Method: The ethanolic crude extract of G. pharnaceoides (Gp.Cr) was prepared and evaluated for phytochemical substances by preliminary screening and HPLC analysis. Anti-inflammatory activity of Gp.Cr (300 and 500 mg/kg) was examined by administration of 200 µl of 7.5% acetic acid intra-rectally to induce ulcerative colitis and colonic mucosal injury, while mucosal homeostasis was evaluated by disease activity index, colonic ulcer score and hematological parameters. Anti-inflammatory potential was quantified by assessing antioxidant enzymes (SOD, CAT, GPX-1), lipid peroxides, nitric oxide and cytokines (IL-1β, IL-6, TNF-α) immunoassays and further analyzed by histological analysis of colon tissues. Results: Phytochemical screening of Gp.Cr revealed the presence of alkaloids, phenols, flavonoids, steroids, tannins and saponins, while HPLC analysis confirmed the presence of quercetin, gallic acid, coumaric and sinapic acid. In acetic acid-induced ulcerative colitis model, Gp.Cr (300 and 500 mg/kg) along with sulphasalazine (500 mg/kg) decreased disease activity index, ulcer scores and hematological parameters. Gp.Cr showed a significant anti-inflammatory potential by increasing antioxidant enzymes and decreasing lipid peroxides, nitric oxide and cytokines levels. Histopathological examination showed significant decline in ulceration and tissue disruption. Conclusion: Hence, the findings confirmed the effectiveness of G. pharnaceoides crude extract in the treatment of ulcerative colitis and might be a promising remedy to manage inflammatory disorders.

scholarly journals Protective Effect ofCalculus Bovis Sativuson Dextran Sulphate Sodium-Induced Ulcerative Colitis in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiping Li ◽  
Yanjiao Xu ◽  
Chengliang Zhang ◽  
Li Deng ◽  
Mujun Chang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Protective Effect ◽  
Activity Index ◽  
Disease Activity Index ◽  
Inflammatory Cells ◽  
Dextran Sulphate ◽  
Colon Tissue ◽  
Sod Activity ◽  
Dextran Sulphate Sodium ◽  
Anti Inflammatory

Calculus Bovis Sativus(CBS) is a commonly used traditional Chinese medicine, which has been reported to exhibit antispasmodic, fever-reducing, anti-inflammatory, and gallbladder-repairing effects. The present study aims to investigate the protective effect of CBS on dextran sulphate sodium- (DSS-) induced ulcerative colitis (UC) in mice. C57BL/6 male mice were exposed to 5% DSS in drinking water. CBS was given orally at 50 and 150 mg/kg once per day for 7 days. Body weight, disease activity index (DAI), colon length, colonic myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and nitric oxide (NO) levels were measured. Administration of CBS significantly reserved these changes, decreased the MPO activity and MDA and NO level, and increased the SOD activity in the colon tissue. Histological observation suggested that CBS alleviated edema, mucosal damage, and inflammatory cells infiltration induced by DSS in the colon. Moreover, CBS significantly downregulated the mRNA expression of tumor necrosis factor-α(TNF-α), interleukin- (IL-) 1βand IL-6 in the colon tissue. Our data suggested that CBS exerted protective effect on DSS-induced UC partially through the antioxidant and anti-inflammatory activities.

scholarly journals Role of Oxidative Stress and Inflammatory Cytokines (TNF-α and IL-6) in Acetic Acid-Induced Ulcerative Colitis in Rats: Ameliorated by Otostegia fruticosa

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 195
Author(s):  
Mohd Nazam Ansari ◽  
Najeeb Ur Rehman ◽  
Aman Karim ◽  
Gamal A. Soliman ◽  
Majid A. Ganaie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Histopathological Examination ◽  
Activity Index ◽  
Disease Activity Index ◽  
Sub Saharan Africa ◽  
Albino Rats ◽  
Inflammatory Score ◽  
Tnf Α

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes irritation, inflammation, and ulceration in the linings of the colon and rectum. Otostegia fruticosa is traditionally used to treat various disorders in different parts of the Middle East and sub-Saharan Africa. In the present study, we evaluated the ameliorative effects of crude leaves extract of O. fruticosa (OF.Cr) on acetic acid (AA)-induced UC model in Wistar albino rats. Wistar rats were administered orally with either vehicle (10 mL/kg), OF.Cr (200 and 400 mg/kg), or prednisolone (2 mg/kg) once a day for 6 days. On day 6, UC was induced in rats by intrarectal administration of a single dose of 5% AA (1.0 mL). Disease activity index (DAI) was recorded after one day of colitis induction by assessing the symptoms of colitis and then the rats were euthanized by cervical dislocation, and colon tissues were isolated for the histopathological examination and biochemical analysis of oxidative stress parameters and cytokines (Interleukin-6 and Tumor Necrosis Factor-α). OF.Cr pretreatment exhibits significant prevention against UC, as confirmed by a significant decrease of DAI, colonic ulceration, and reduced inflammatory score as compared to the AA-induced colitis rats. Depletion of total glutathione (GSH) levels and catalase (CAT) activities in the colitis group was significantly restored in the OF.Cr treated groups, while increased lipid peroxidation in the colon tissues was significantly reduced. OF.Cr prevented the activation of the IL-6 and TNF-α pathways in the colonic tissues, which were clearly observed by the decreased levels of IL-6 and TNF-α in the OF.Cr treated animals. Hence, OF.Cr could be developed in the future for the treatment of UC.

scholarly journals The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Teng ◽  
Jie Hao ◽  
Hui Bi ◽  
Congcong Li ◽  
Yongfeng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Activity Index ◽  
Disease Activity Index ◽  
Protective Effects ◽  
Protein Protein Interactions ◽  
Anti Inflammatory ◽  
Factor Α

Background: In China, the incidence of ulcerative colitis (UC) is increasing every year, but the etiology of UC remains unclear. UC is known to increase the risk of colorectal cancer (CRC). The aim of this study was to investigate the protective effects of crocin against UC and CRC in mouse models.Methods: Crocin was used to treat the dextran sodium sulfate (DSS)-induced UC mice for 3 weeks, and ApcMinC/Gpt mice with colorectal cancer for 8 weeks. Proteomics screening was used to detect changes in the protein profiles of colon tissues of UC mice. Enzyme-linked immunosorbent assays and western blot were used to verify these changes.Results: Crocin strongly reduced the disease activity index scores of UC mice, and improved the pathological symptoms of the colonic epithelium. The anti-inflammatory effects of crocin were indicated by its regulation of the activity of various cytokines, such as interleukins, via the modulation of nuclear factor kappa-B (NF-κB) signaling. Crocin significantly suppressed tumor growth in ApcMinC/Gpt mice and ameliorated pathological alterations in the colon and liver, but had no effects on spleen and kidney. Additionally, crocin significantly decreased the concentrations of interleukins and tumor necrosis factor-α in the sera and colon tissues, suggesting its anti-inflammatory effects related to NF-κB signaling. Finally, 12-h incubation of SW480 cells with crocin caused cell cycle arrest, enhanced the apoptotic rate, promoted the dissipation of mitochondrial membrane potential, and the over-accumulation of reactive oxygen species. From the theoretical analyses, phosphorylated residues on S536 may enhance the protein-protein interactions which may influence the conformational changes in the secondary structure of NF-κB.Conclusion: The protective effects of crocin on UC and CRC were due to its suppression of NF-κB-mediated inflammation.

scholarly journals Galectin-1 reduces the severity of ulcerative colitis induced by dextran sulfate sodium via suppressing inflammatory and oxidative mediators

2020 ◽  
Author(s):  
Pelin Arda-Pirincci ◽  
Guliz Aykol-Celik
Keyword(s):  
Ulcerative Colitis ◽  
Cell Proliferation ◽  
Body Weight ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Proliferation Index ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory

Ulcerative colitis is an inflammatory bowel disease and many people suffers from this disease across the word. Dextran sulfate sodium (DSS) is a synthetic sulfated polysaccharide that is used to produce ulcerative colitis in rodents. Galectin-1 is a β-galactoside binding animal lectin which plays key roles in many biological events. In this study, we investigated the role of galectin-1 on colon morphology, cell proliferation, oxidative stress, anti-oxidant system, inflammatory and anti-inflammatory mediators in the model of experimental ulcerative colitis induced by DSS in mice. C57BL/6  mice were fed orally 3% DSS in their drinking water for 5 days for acute colitis induction. Animals were injected with 1 mg/kg recombinant human galectin-1 for 7 consecutive days. Oral DSS application resulted in colitis injury by causing histopathological changes; an increase in disease activity index (DAI), lipid peroxidation (MDA), myeloperoxidase (MPO) and TNF-α levels; a decrease in body weight, colon length, cell proliferation index, catalase (CAT), glutahione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, gluathione (GSH) and IL-10 levels. However, treatment with galectin-1 prevented DSS-induced colitis injury through the reduction of DAI, MDA, MPO and TNF-α levels, and the increase of body weight, colon length, cell proliferation, antioxidant enzymes activities, GSH and IL-10 levels. As a result, this study showed that galectin-1 has proliferative, anti-oxidant, anti-inflammatory, and cytoprotective effects against DSS-induced colitis in mice. In addition, galectin-1 reduces the severity of ulcerative colitis via suppressing inflammatory and oxidative mediators.

scholarly journals The Bisindole Alkaloid Caulerpin, from Seaweeds of the Genus Caulerpa, Attenuated Colon Damage in Murine Colitis Model

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 318 ◽  
Author(s):  
Alessandra Lucena ◽  
Cássio Souza ◽  
Jéssica Jales ◽  
Paulo Guedes ◽  
George de Miranda ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Activity Index ◽  
Disease Activity Index ◽  
Colon Tissue ◽  
Inflammatory Infiltration ◽  
Tissue Samples ◽  
Murine Colitis ◽  
Tnf Α ◽  
Effective Doses

Caulerpin (CLP), an alkaloid from algae of the genus Caulerpa, has shown anti-inflammatory activity. Therefore, this study aimed to analyze the effect of CLP in the murine model of peritonitis and ulcerative colitis. Firstly, the mice were submitted to peritonitis to evaluate which dose of CLP (40, 4, or 0.4 mg/kg) could decrease the inflammatory infiltration in the peritoneum. The most effective doses were 40 and 4 mg/kg. Then, C57BL/6 mice were submitted to colitis development with 3% dextran sulfate sodium (DSS) and treated with CLP at doses of 40 and 4 mg/kg. The disease development was analyzed through the disease activity index (DAI); furthermore, colonic tissue samples were submitted to histological analysis, NFκB determination, and in vitro culture for cytokines assay. Therefore, CLP at 4 mg/kg presented the best results, triggering improvement of DAI and attenuating the colon shortening and damage. This dose was able to reduce the TNF-α, IFN-γ, IL-6, IL-17, and NFκB p65 levels, and increased the levels of IL-10 in the colon tissue. Thus, CLP mice treatment at a dose of 4 mg/kg showed promising results in ameliorating the damage observed in the ulcerative colitis.

scholarly journals Comparative Study of Anti-Inflammatory Effect on DSS-Induced Ulcerative Colitis Between Novel Glycyrrhiza Variety and Official Compendia

2021 ◽  
Vol 11 (4) ◽  
pp. 1545
Author(s):  
Sa-Haeng Kang ◽  
Young-Jae Song ◽  
Yong-Deok Jeon ◽  
Dong-Keun Kim ◽  
Jeong-Hyang Park ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Activity Index ◽  
Clinical Signs ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Fecal Microbiota ◽  
Specific Pattern ◽  
Plant Cultivation ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Glycyrrhizae radix (GR), a plant commonly referred to as licorice, is used as a medicine and food worldwide. However, the utilization of GR from wild areas has caused desertification and a depletion of natural resources. Environmental restrictions and low productivity have limited plant cultivation. For this reason, an improved Glycyrrhiza variety, Wongam (WG), in cultivation and quality has been developed by Korea Rural Development Administration. To evaluate the equivalence of efficacy, several comparative studies between already-registered species and new cultivars have been conducted. This study evaluated the anti-inflammatory effect of WG extracts in a dextran sulfate sodium (DSS)-induced colitis model, in comparison to that of GR extracts. WG extract significantly improved the clinical signs of DSS-induced ulcerative colitis, including disease activity index, body weight loss, and colon length shortening, which was equivalent to the effect of GR. Furthermore, the fecal microbiota was analyzed by terminal restriction fragment length polymorphism. The composition of the fecal microbiota did not show a specific pattern based on experimental groups; however, a tendency toward an increase in the proportion of Lactobacillales was observed. These findings showed an equivalence of efficacy and the possible utilization of WG as a medicinal resource with already-registered species.

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