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

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.

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The CD200 Regulates Inflammation in Mice Independently of TNF-α Production

International Journal of Molecular Sciences ◽

10.3390/ijms22105358 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5358

Author(s):

Katarzyna Tonecka ◽

Agata Braniewska ◽

Zofia Pilch ◽

Zuzanna Sas ◽

Marcin Skorzynski ◽

...

Keyword(s):

Immune Cells ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Histological Evaluation ◽

Bodyweight Loss ◽

Colon Tissue ◽

Tnf Α

Inflammatory bowel disease is characterized by the infiltration of immune cells and chronic inflammation. The immune inhibitory receptor, CD200R, is involved in the downregulation of the activation of immune cells to prevent excessive inflammation. We aimed to define the role of CD200R ligand-CD200 in the experimental model of intestinal inflammation in conventionally-reared mice. Mice were given a dextran sodium sulfate solution in drinking water. Bodyweight loss was monitored daily and the disease activity index was calculated, and a histological evaluation of the colon was performed. TNF-α production was measured in the culture of small fragments of the distal colon or bone marrow-derived macrophages (BMDMs) cocultured with CD200+ cells. We found that Cd200−/− mice displayed diminished severity of colitis when compared to WT mice. Inflammation significantly diminished CD200 expression in WT mice, particularly on vascular endothelial cells and immune cells. The co-culture of BMDMs with CD200+ cells inhibited TNF-α secretion. In vivo, acute colitis induced by DSS significantly increased TNF-α secretion in colon tissue in comparison to untreated controls. However, Cd200−/− mice secreted a similar level of TNF-α to WT mice in vivo. CD200 regulates the severity of DSS-induced colitis in conventionally-reared mice. The presence of CD200+ cells decreases TNF-α production by macrophages in vitro. However, during DDS-induced intestinal inflammation secretion of TNF-α is independent of CD200 expression.

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ROLE OF ANTIOXIDANT AND MYELOPEROXIDASE LEVELS IN 7, 12-DIMETHYLBENZ [A] ANTHRACENE INDUCED EXPERIMENTAL RAT MODEL: EVIDENCE FOR OXIDATIVE DAMAGE IN ACTIVE ULCERATIVE COLITIS.

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i3.16485 ◽

2017 ◽

Vol 9 (3) ◽

pp. 282

Author(s):

P. Geetha ◽

B. Lakshman Kumar ◽

U. Indra ◽

B. Pavithra Sheetal

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Antioxidant Status ◽

Activity Index ◽

Disease Activity Index ◽

The Body ◽

Unknown Etiology ◽

Steady Increase ◽

Tissue Samples ◽

Significant Change

Objective: Ulcerative colitis known as inflammatory bowel disease (IBD) of unknown etiology. We examined the antioxidant and myeloperoxidase status in a murine model of 7,12-dimethylbenz[a]anthracene induced colitis to elucidate the exact mechanism behind the inflammation.Methods: Male Wistar rats were exposed to ulcerative colitis using various concentration of DMBA (7,12-Dimethylbenz[A]anthracene) were periodically analysed on 4th, 8th, 12th, 24th and 32nd week from the date of induction. To determine the disease activity index changes in body weight, food consumption, the presence of gross blood in stool and consistency of feces and diarrhea were observed. Macroscopic characters were elucidated based on clinical features of the colon and rectum using scoring pattern. Tissue inflammation status was noted through myeloperoxidase (MPO) assay. The antioxidant status in tissue samples was analysed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total reduced glutathione (GSH).Results: Gavage intubation of DMBA induced colitis showed significant changes from 4th week and severity on 32nd week. The body weight was gradually reduced. Macroscopic scoring showed severe scoring pattern the inflammation was significantly heavier by week 4; and by the end of 32 w, inflammation in rats was double that of the controls, tissue myeloperoxidase (MPO) activity showed the steady increase of neutrophil infiltration and inflammation rate every week. A significant change was noted in tissue antioxidant status and it showed the oxidation level. Statistically, significant change was recorded from 4th week till 32nd week.Conclusion: The conventional biochemical changes in colitis induced animal model revealed the association between the oxidative stress and ulcerative colitis.

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Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways

BioMed Research International ◽

10.1155/2021/5561221 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xinghan Zheng ◽

Liting Mai ◽

Tongtong Wang ◽

Ying Xu ◽

Zireng Su ◽

...

Keyword(s):

Signaling Pathways ◽

Activity Index ◽

Disease Activity Index ◽

Protective Effects ◽

Intestinal Epithelial ◽

Colon Tissue ◽

Epithelial Barrier Function ◽

Brucea Javanica ◽

Tnf Α ◽

Brucea Javanica Oil

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.

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A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90496.2008 ◽

2009 ◽

Vol 296 (6) ◽

pp. G1167-G1179 ◽

Cited By ~ 107

Author(s):

Ryan Ungaro ◽

Masayuki Fukata ◽

David Hsu ◽

Yasmin Hernandez ◽

Keith Breglio ◽

...

Keyword(s):

Activity Index ◽

Disease Activity Index ◽

Mucosal Healing ◽

Transfer Model ◽

Innate Immune Responses ◽

Murine Colitis ◽

Dss Colitis ◽

Tnf Α ◽

Inflammatory Bowel ◽

Intestinal Repair

Dysregulated innate immune responses to commensal bacteria contribute to the development of inflammatory bowel disease (IBD). TLR4 is overexpressed in the intestinal mucosa of IBD patients and may contribute to uncontrolled inflammation. However, TLR4 is also an important mediator of intestinal repair. The aim of this study is to examine the effect of a TLR4 antagonist on inflammation and intestinal repair in two murine models of IBD. Colitis was induced in C57BL/6J mice with dextran sodium sulfate (DSS) or by transferring CD45Rbhi T cells into RAG1−/− mice. An antibody (Ab) against the TLR4/MD-2 complex or isotype control Ab was administered intraperitoneally during DSS treatment, recovery from DSS colitis, or induction of colitis in RAG1−/− mice. Colitis severity was assessed by disease activity index (DAI) and histology. The effect of the Ab on the inflammatory infiltrate was determined by cell isolation and immunohistochemistry. Mucosal expression of inflammatory mediators was analyzed by real-time PCR and ELISA. Blocking TLR4 at the beginning of DSS administration delayed the development of colitis with significantly lower DAI scores. Anti-TLR4 Ab treatment decreased macrophage and dendritic cell infiltrate and reduced mucosal expression of CCL2, CCL20, TNF-α, and IL-6. Anti-TLR4 Ab treatment during recovery from DSS colitis resulted in defective mucosal healing with lower expression of COX-2, PGE2, and amphiregulin. In contrast, TLR4 blockade had minimal efficacy in ameliorating inflammation in the adoptive transfer model of chronic colitis. Our findings suggest that anti-TLR4 therapy may decrease inflammation in IBD but may also interfere with colonic mucosal healing.

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

Scientific Reports ◽

10.1038/srep25672 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 10

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.

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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

10.21203/rs.3.rs-31454/v1 ◽

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.

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Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase

International Journal of Oral Science ◽

10.1038/s41368-021-00136-2 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Xida Zhao ◽

Jingbo Liu ◽

Chong Zhang ◽

Ning Yu ◽

Ze Lu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Porphyromonas Gingivalis ◽

Th17 Cell ◽

Inflammatory Responses ◽

Activity Index ◽

Peptidylarginine Deiminase ◽

T Helper 17 ◽

Colon Tissue ◽

Cell Numbers

AbstractUlcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0−40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31−40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.

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

Journal of Clinical Medicine ◽

10.3390/jcm8122086 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2086 ◽

Cited By ~ 1

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.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/469506 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 11

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.

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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 ◽

10.3390/life11030195 ◽

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.

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