The combination of indirubin and isatin attenuates dextran sodium sulfate induced ulcerative colitis in mice

2018 ◽  
Vol 96 (5) ◽  
pp. 636-645 ◽  
Author(s):  
Wenyan Gao ◽  
Luding Zhang ◽  
Xiaoqian Wang ◽  
Li Yu ◽  
Changhong Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Body Mass ◽  
Inflammatory Diseases ◽  
Activity Index ◽  
Single Agent ◽  
Disease Activity Index ◽  
Mapk Signaling ◽  
Protective Effects ◽  
Epithelial Cell Apoptosis ◽  
Anti Inflammatory

Indirubin and isatin have been used in the treatment of inflammatory diseases due to their anti-inflammatory properties. This study aimed to evaluate the combined effect of indirubin and isatin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). UC was induced by the administration of 3% (w/v) DSS solution, and then the model mice were administered indirubin (10 mg/kg body mass) and (or) isatin (10 mg/kg body mass) by gavage once daily for 7 days. The results showed that indirubin and isatin, individually or combined, significantly inhibited weight loss, lowered disease activity index (DAI), ameliorated pathological changes, decreased the levels of pro-inflammatory mediators and myeloperoxidase (MPO) activity, increased the expression of anti-inflammatory cytokines and Foxp3, suppressed CD4+ T cell infiltration, and inhibited oxidative stress and epithelial cell apoptosis. Additionally, indirubin and isatin, both individually and combined, can also inhibit activation of the NF-κB and MAPK pathways induced by DSS. The protective effect of combination therapy against UC was superior to that of single-agent treatment. These results suggest that indirubin combined with isatin attenuates DSS-induced UC, and changes to the NF-κB and MAPK signaling pathways may mediate the protective effects of indirubin and isatin in 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 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 Extraintestinal Helminth Infection Limits Pathology and Proinflammatory Cytokine Expression during DSS-Induced Ulcerative Colitis: A Role for Alternatively Activated Macrophages and Prostaglandins

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Yadira Ledesma-Soto ◽  
Blanca E. Callejas ◽  
César A. Terrazas ◽  
Jose L. Reyes ◽  
Arlett Espinoza-Jiménez ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Activity Index ◽  
Disease Activity Index ◽  
Helminth Parasites ◽  
Activated Macrophages ◽  
Alternatively Activated Macrophages ◽  
Arginase 1 ◽  
Alternatively Activated

Chronic inflammation of the intestinal mucosa is characteristic of inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. Helminth parasites have developed immunomodulatory strategies that may impact the outcome of several inflammatory diseases. Therefore, we investigated whetherTaenia crassicepsinfection is able to decrease the inflammatory effects of dextran sulfate sodium- (DSS-) induced ulcerative colitis in BALB/c and C57BL/6 mice. Preinfection significantly reduced the manifestations of DSS-induced colitis, as weight loss and shortened colon length, and decreased the disease activity index independently of the genetic background of the mice.Taeniainfection decreased systemic levels of proinflammatory cytokines while increasing levels of IL-4 and IL-10, and the inflammatory infiltrate into the colon was also markedly reduced. RT-PCR assays from colon showed thatT. crassiceps-infected mice displayed increased expression of Arginase-1 but decreased expression of iNOS compared to DSS-treated uninfected mice. The percentages of T regulatory cells were not increased. The adoptive transfer of alternatively activated macrophages (AAMФs) from infected mice into mice with DSS-induced colitis reduced the severity of colon inflammation. Administration of indomethacin abrogated the anticolitic effect ofTaenia. Thus,T. crassicepsinfection limits the pathology of ulcerative colitis by suppressing inflammatory responses mechanistically associated with AAMФs and prostaglandins.

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.

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 Interference With the AMPKα/mTOR/NLRP3 Signaling and the IL-23/IL-17 Axis Effectively Protects Against the Dextran Sulfate Sodium Intoxication in Rats: A New Paradigm in Empagliflozin and Metformin Reprofiling for the Management of Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmoud Youssef ◽  
Eslam Abd El-Fattah ◽  
Amir Abdelhamid ◽  
Hanan Eissa ◽  
Eman El-Ahwany ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cell ◽  
Activity Index ◽  
Damage Index ◽  
Cell Polarization ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Ampk Phosphorylation ◽  
T Cell Polarization ◽  
Anti Inflammatory

Empagliflozin and metformin are widely used for the treatment of type 2 diabetes. These drugs showed marked anti-inflammatory effects in different animal models via enhancing AMPK activity. Yet, the protective anti-inflammatory effects of their combination against ulcerative colitis have not been previously investigated. The current study aimed to explore the potential of empagliflozin/metformin combination to mitigate the DSS-induced rat colitis model. The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated. In this study, distal colons were examined for macroscopic and microscopic pathological alterations. ELISA, qRT-PCR, and immunohistochemistry techniques were applied to detect proteins and cytokines involved in AMPK/mTOR/NLRP3 axis and T Cell polarization. Oral administration of empagliflozin (10 mg/kg/day) and metformin (200 mg/kg/day) combination alleviated colitis as revealed by the reduced disease activity index, macroscopic damage index, colon weight/length ratio, and histopathologic scoring values. Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Reduced mTOR expression and reduced IL-6 levels led to a reduction in Th17 cell polarization and maintenance. Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated via enhancing AMPK phosphorylation. Since adult humans with diabetes mellitus are at greater risk for developing inflammatory bowel diseases, clinical application of empagliflozin/metformin combination represents a novel therapeutic approach for treating diabetic patients with ulcerative colitis.

scholarly journals Anti-Inflammatory Effects of Heritiera littoralis Fruits on Dextran Sulfate Sodium- (DSS-) Induced Ulcerative Colitis in Mice by Regulating Gut Microbiota and Suppressing NF-κB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Guosheng Lin ◽  
Minyao Li ◽  
Nan Xu ◽  
Xiaoli Wu ◽  
Jingjing Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Disease Activity Index ◽  
Rrna Gene ◽  
Chemical Compositions ◽  
Protective Effects ◽  
Esi Ms

Aim of the Study. This study is aimed at exploring the effects and pharmacological mechanisms of the extracts from the Heritiera littoralis fruit (EFH) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) in mice. Materials and Methods. The chemical compositions of EFH were identified using LC-ESI-MS. The mice with 3% DSS-induced UC were administered EFH (200, 400, and 800 mg/kg), sulfasalazine (SASP, 200 mg/kg), and azathioprine (AZA, 13 mg/kg) for 10 days via daily gavage. The colonic inflammation was evaluated by the disease activity index (DAI), colonic length, histological scores, and levels of inflammatory mediators. The gut microbiota was characterized by 16S rRNA gene sequencing and analysis. Results. LC-ESI-MS analysis showed that EFH was rich in alkaloids and flavones. The results indicated that EFH significantly improved the DAI score, relieved colon shortening, and repaired pathological colonic variations in colitis. In addition, proteins in the NF-κB pathway were significantly inhibited by EFH. Furthermore, EFH recovered the diversity and balance of the gut microbiota. Conclusions. EFH has protective effects against DSS-induced colitis by keeping the balance of the gut microbiota and suppressing the NF-κB pathway.

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.

scholarly journals In Vitro Antioxidant, Anti-inflammatory, and In Vivo Anticolitis Effects of Combretin A and Combretin B on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Mbiantcha Marius ◽  
Dawe Amadou ◽  
Atsamo Albert Donatien ◽  
Ateufack Gilbert ◽  
Yousseu Nana William ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ulcerative Colitis ◽  
Protein Denaturation ◽  
Antioxidant Activities ◽  
Activity Index ◽  
Antioxidant Properties ◽  
Disease Activity Index ◽  
Anti Inflammatory

Combretum fragrans (Combretaceae) is a Cameroonian medicinal plant containing various secondary metabolites and traditionally used for the treatment of several pathologies. Two cycloartane-type triterpenes, Combretin A and Combretin B, were isolated from this plant. This study was aimed at evaluating the anti-inflammatory, antioxidant, and anticolitis effects of these compounds. In vitro anti-inflammatory properties were evaluated by inhibition of cyclooxygenase, 5-lipoxygenase, and denaturation of the protein; antioxidant properties were assessed by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), (2,2’-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) ABTS•+, capacity tests ferric reducing antioxidant (FRAP), and trapping nitric oxide. For in vivo analysis, we used the model of ulcerative colitis induced by Dextran Sulfate Sodium (DSS). Studies of the anti-inflammatory activity showed that Combretin A and Combretin B had maximal inhibitory activity on cyclooxygenase (71.92% and 89.59%), 5-lipoxygenase (76.68% and 91.21%), and protein denaturation (63.93% and 87.78%). Antioxidant activity on DPPH, ABTS•+, ferric reducing antioxidant capacity (FRAP), and nitric oxide scavenging showed that Combretin A and Combretin B showed good antioxidant activities. These compounds significantly reduced the signs of DSS-induced colitis in the treated animals by preventing the weight loss of the animals, by significantly reducing the disease activity index, improving the condition of the stool, preventing the reduction of the length of the colon, and preventing the degradation of the colon. This study revealed that Combretin A and Combretin B have anti-inflammatory, antioxidant, and curative properties against colitis experimentally induced by DSS in rats.

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