Ficus pandurata Hance Inhibits Ulcerative Colitis and Colitis-Associated Secondary Liver Damage of Mice by Enhancing Antioxidation Activity

Inflammatory bowel disease (IBD), a global disease threatening human health, is commonly accompanied by secondary liver damage (SLD) mediated by the gut-liver axis. Oxidative stress acts a critical role in the onset of IBD, during which excessive oxidation would destroy the tight junctions between intestinal cells, promote proinflammatory factors to penetrate, and thereby damage the intestinal mucosa. Ficus pandurata Hance (FPH) is widely used for daily health care in South China. Our previous study showed that FPH protected acute liver damage induced by alcohol. However, there is no study reporting FPH treating ulcerative colitis (UC). This study is designed to investigate whether FPH could inhibit UC and reveal its potential mechanism. The results showed that FPH significantly alleviated the UC disease symptoms including the body weight loss, disease activity index (DAI), stool consistency changing, rectal bleeding, and colon length loss of UC mice induced by dextran sulfate sodium (DSS) and reversed the influences of DSS on myeloperoxidase (MPO) and diamine oxidase activity (DAO). FPH suppressed UC via inhibiting the TLR4/MyD88/NF-κB pathway and strengthened the gut barrier of mice via increasing the expressions of ZO-1 and occludin and enhancing the colonic antioxidative stress property by increasing the levels of T-SOD and GSH-Px and the expressions of NRF2, HO-1, and NQO1 and reducing MDA level and Keap1, p22-phox, and NOX2 expressions. Furthermore, FPH significantly inhibited SLD related to colitis by reducing the abnormal levels of the liver index, ALT, AST, and cytokines including TNFα, LPS, LBP, sCD14, and IL-18 in the livers, as well as decreasing the protein expressions of NLRP3, TNFα, LBP, CD14, TLR4, MyD88, NF-κB, and p-NF-κB, suggesting that FPH alleviated UC-related SLD via suppressing inflammation mediated by inhibiting the TLR4/MyD88/NF-κB pathway. Our study firstly investigates the anticolitis pharmacological efficacy of FPH, suggesting that it can be enlarged to treat colitis and colitis-associated liver diseases in humans.

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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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The protective effect of curcumin on rats with DSS-induced ulcerative colitis and its mechanisms

10.21203/rs.3.rs-191627/v1 ◽

2021 ◽

Author(s):

Jing Guo ◽

Yan-yan Zhang ◽

Mei Sun ◽

Ling-fen Xu

Keyword(s):

Ulcerative Colitis ◽

Th17 Cells ◽

Dextran Sulfate ◽

Activity Index ◽

Disease Activity Index ◽

Treg Cells ◽

Enzyme Linked Immunosorbent Assay ◽

T Helper ◽

T Helper 17 ◽

Inflammatory Bowel

Abstract Aim This study aimed to explore effect of curcumin on inflammatory bowel disease (IBD) in rats and its mechanism.Methods: A dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) rat model was established. The disease activity index (DAI) scores were calculated. The histopathological damage scores were determined by haematoxylin-eosin (H&E) staining. Regulatory T (Treg) cells and T helper 17 (Th17) cells in the spleen were analysed by flow cytometry. The levels of interleukin (IL)-10 and IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the DSS model group, the curcumin group exhibited significantly reduced DAI scores and improvements in histopathological damage. The expression of CD4+IL-17+ Th17 cells was significantly lower and the expression of CD4+CD25+Foxp3+ Treg cells was significantly higher in the curcumin group than in the DSS group.Conclusion: Curcumin may be a new and effective treatment for IBD by regulating the balance of Treg/Th17 cells and the expression of IL-10 and IL-17A.

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Validation of the “German Inflammatory Bowel Disease Activity Index (GIBDI)”: An Instrument for Patient-Based Disease Activity Assessment in Crohn’s Disease and Ulcerative Colitis

Zeitschrift für Gastroenterologie ◽

10.1055/a-0605-4080 ◽

2018 ◽

Vol 56 (10) ◽

pp. 1267-1275 ◽

Cited By ~ 1

Author(s):

Angelika Hüppe ◽

Jana Langbrandtner ◽

Winfried Häuser ◽

Heiner Raspe ◽

Bernd Bokemeyer

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Disease Activity Index ◽

Inflammatory Bowel ◽

Activity Indices

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

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P049 A new preclinical rationale for first-line therapy of ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.178 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S157-S157

Author(s):

H Thorlacius ◽

A Bjoerk ◽

Ö Nordle ◽

G Hedlund

Keyword(s):

Ulcerative Colitis ◽

Activity Index ◽

Body Weight Loss ◽

Disease Activity Index ◽

Therapeutic Effects ◽

Aminosalicylic Acid ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Chronic Inflammatory Condition

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory condition with no known medical cure. 5-Aminosalicylic acid (5-ASA [mesalazine]) represents the cornerstone of first-line therapy for mild-to-moderate UC. Sulfasalazine (SASP) is the original agent in this class of drugs. Meta-analyses of patients with mild-to-moderately active UC comparing 5-ASA to placebo showed 5-ASA to be significantly superior to placebo. However, about two-thirds of patients treated with 5-ASA fail to enter clinical remission. It is therefore most important to identify strategies to accelerate and maximise the therapeutic effects of 5-ASA. Therapeutic intervention against NFκB activation is a useful strategy for treatment of UC. The 4-alkanoylaminobenzamide PM0503 inhibits the breakdown of the NFκB inhibitor IκBβ, and SASP/5-ASA inhibits the breakdown of IκBα. This elicited a hypothesis of a possible synergistic action and converging effect on NFκB signalling. In the present study, we investigated the effect of combining SASP/5-ASA with PM0503 in experimental colitis. Methods SASP and PM0503 alone or in combination were administered for 5 days to Balb/c mice with colitis triggered by 5% dextran sulphate sodium (DSS). Blood in the stool, stool consistency and body weight loss were evaluated daily on a 0–4 point scale. The disease activity index (DAI) was calculated by summarising the total score of these three parameters. Results Addition of 5% DSS in the drinking water for 5 days produced reproducible symptoms of colitis. PM0503 was shown to inhibit DSS induced colitis by reducing mean DAI at day 5 from 6.9 in controls to 1.7 (a 75% decrease). Mean DAI recorded with SASP treatment at optimal doses in the same series of experiments was 4.4 (a 36% decrease). Furthermore, and most important, lower doses of PM0503 acted synergistically with SASP in ameliorating DSS-induced disease severity. The combination of PM0503 and SASP using suboptimal doses having minimal beneficial effects as monotherapies, showed more than 50% disease inhibition at day 5. In addition, no toxicity was observed with PM0503 alone or in combination with SASP. Conclusion Our findings offer a preclinical rationale for simultaneous coadministration of PM0503 and a 5-ASA agent such as SASP or 5-ASA as first-line treatment for patients with UC.

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Bifidobacterium longum subsp. infantis BB-02 attenuates acute murine experimental model of inflammatory bowel disease

Beneficial Microbes ◽

10.3920/bm2014.0070 ◽

2015 ◽

Vol 6 (3) ◽

pp. 277-286 ◽

Cited By ~ 16

Author(s):

S.D.A. Elian ◽

E.L.S. Souza ◽

A.T. Vieira ◽

M.M. Teixeira ◽

R.M.E. Arantes ◽

...

Keyword(s):

Ulcerative Colitis ◽

Activity Index ◽

Protective Action ◽

Bifidobacterium Longum ◽

Immunoglobulin A ◽

Disease Activity Index ◽

Preventive Strategy ◽

Probiotic Potential ◽

Inflammatory Conditions ◽

Inflammatory Bowel

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions, characterised by remissions and relapses episodes, whose main manifestations are ulcerative colitis and Crohn's disease. Ulcerative colitis (UC), one of the main forms of IBD, has as standard treatment the use of corticosteroids and anti-inflammatory drugs. The use of antibiotics has been also reported, but the possible adverse effects, such as disturbance of the indigenous microbiota or resistance induction, should be taken into consideration, and thus the use of probiotics emerges as a possible alternative option of treatment. In this study, the oral administration of Bifidobacterium longum subsp. infantis BB-02 was evaluated as a preventive strategy for acute experimental UC induced in female BALB/c mice by ingestion of 3.5% dextran sulphate sodium in drinking water during 7 days. During this time, the daily disease activity index was evaluated, and on the seventh day the animals were euthanised to collect intestines and liver for analysis. Treatment with the probiotic resulted in clinical improvement of the animals. The histological and morphometric analyses showed a reduction of lesions and oedema in the gut, but there was no increase in the production of mucin. The dosage of secretory immunoglobulin A was significantly higher in the colitis group and reduced in the group treated with the probiotic. There was also a reduction in the inflammation of the colon, as demonstrated by a decrease in neutrophils infiltration, and KC/CXCL-1 levels. The intestinal permeability, which is typically increased during the onset of IBD, was also reduced by treatment with probiotic. Based on these data, it can be concluded that the bacterium B. infantis BB-02 has a probiotic potential for the attenuation of UC, but further studies should be conducted to verify the mechanism of protective action of the bacterium.

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Short-Chain Naphthoquinone Protects Against Both Acute and Spontaneous Chronic Murine Colitis by Alleviating Inflammatory Responses

Frontiers in Pharmacology ◽

10.3389/fphar.2021.709973 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sonia Shastri ◽

Tanvi Shinde ◽

Krystel L. Woolley ◽

Jason A. Smith ◽

Nuri Gueven ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Inflammatory Responses ◽

Activity Index ◽

Critical Role ◽

Intestinal Barrier ◽

Body Weight Loss ◽

Disease Activity Index ◽

Sodium Sulphate ◽

Short Chain ◽

Cytokines And Chemokines

Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.

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Chlamydia muridarum Alleviates Colitis via the IL-22/Occludin Signal Pathway

BioMed Research International ◽

10.1155/2020/8894331 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Xin Wang ◽

Huai-cai Zeng ◽

Yan-ru Huang ◽

Qing-zhi He

Keyword(s):

Ulcerative Colitis ◽

Activity Index ◽

Disease Activity Index ◽

Signal Pathway ◽

Colonic Tissue ◽

Chlamydia Muridarum ◽

Interleukin 22 ◽

Downstream Effector ◽

Gastrointestinal Tissue ◽

Inflammatory Bowel

Ulcerative colitis (UC) is the most common inflammatory bowel disease, and its incidence has increased in recent years. Recent clinical and experimental data indicate that gut microbiota plays a pivotal role in the pathogenesis of UC. Chlamydia establishes a stable and persistent colonization in the gastrointestinal tract without apparent pathogenicity to gastrointestinal or extragastrointestinal tissues. However, the detailed effects of Chlamydia on the gastrointestinal tissue remain unknown. The primary aim of this study is to investigate the effects of Chlamydia muridarum (C. muridarum) on development of colitis induced by dextran sodium sulfate (DSS) and the underlying molecular mechanism. The results suggested that C. muridarum significantly improved colitis symptoms—including weight loss, disease activity index, colon length, and histopathological changes in the colon caused by DSS—and alleviated the reduced expression of interleukin-22 and occludin in the colonic tissue due to DSS administration. Furthermore, the absence of IL-22 completely prevented C. muridarum from alleviating colitis and significantly decreased the levels of occludin, an important downstream effector protein of IL-22. These findings suggest that C. muridarum ameliorates ulcerative colitis induced by DSS via the IL-22/occludin signal pathway.

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

Applied Sciences ◽

10.3390/app11041545 ◽

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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Calibrated automated thrombin generation in paediatric patients with inflammatory bowel disease

Hämostaseologie ◽

10.1055/s-0037-1621491 ◽

2009 ◽

Vol 29 (S 01) ◽

pp. S90-S93 ◽

Cited By ~ 4

Author(s):

H. Bernhard ◽

A. Deutschmann ◽

B. Leschnik ◽

M. Novak ◽

A. Hauer ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Disease Activity ◽

Bowel Disease ◽

Thrombin Generation ◽

Activity Index ◽

Disease Activity Index ◽

Healthy Controls ◽

Inflammatory Bowel

SummaryIn adults, inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolic complications. The pathogenesis of IBD is not really clear and a high thrombin activity might contribute to disease progression. We wanted to see whether children with IBD have a higher thrombin generation (TG). Patients, material, methods: Plasma samples were collected of 20 patients with IBD and of 60 healthy controls (age range from 10 to 19). TG was measured by means of Calibrated automated thrombography (CAT). The disease activity was estimated, using the Pediatric Crohn‘s Disease Activity Index (PCDAI) for Crohn‘s disease and the Pediatric Ulcerative Colitis Disease Activity Index (PUCAI) for Ulcerative Colitis. In addition, we investigated F1+F2, TAT, TFPI and fibrinogen. Results: There was a significant increase of endogenous thrombin potential (ETP), lag time and time to peak in patients with IBD, while peak showed no difference to healthy controls. ETP and F1+F2 in children with IBD also showed a significant correlation with PCDAI (PUCAI) and fibrinogen. Conclusion: IBD in children is associated with high TG, but this seems to be caused mainly by the inflammatory process and not by any individual disposition.

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Potential clinical treatment of colitis with cardiotrophin-1

Clinical Science ◽

10.1042/cs20171626 ◽

2018 ◽

Vol 132 (20) ◽

pp. 2169-2174 ◽

Cited By ~ 1

Author(s):

Xavier Escoté

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Activity Index ◽

Disease Activity Index ◽

Tnf Α ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Factor Α

In a recent issue of Clinical Science, Prieto-Vicente et al. [Clin. Sci. (2018) 132, 985–1001] have smartly demonstrated a potential new use of cardiotrophin-1 (CT-1) to treat and palliate an inflammatory bowel disease such as ulcerative colitis. In that work, authors report that in ulcerative colitic mice, administration of exogenous recombinant CT-1 (rCT-1) promotes lower colon damage and lower disease activity index, reducing systemic levels of tumor necrosis factor α (TNF-α) and also diminishing TNF-α expression in colon together with the reduction in other common inflammation markers. Besides, in vivo rCT-1 administration induces activation of several molecular pathways, including nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)-3, and abolishes bacterial translocation from intestine to other organs, including mesenteric ganglia, lungs, and spleen. Additionally, these results were nicely corroborated in CT-1 depleted mice; in which colon damage and ulcerative colitis severity were greater compared with the wild-type counterparts. All together, these results suggested that CT-1 could be a promising new therapeutic approach for treating inflammatory bowel disease, particularly ulcerative colitis. However, further studies are required to determine its major mechanisms of action and the potential efficacy of CT-1 in human inflammatory bowel diseases.

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