Renovation of Intestinal Barrier by Polydatin in Experimentally Induced Ulcerative Colitis: Comparative Ultrastructural Study with L-Carnosine

2021 ◽  
Vol 210 (4) ◽  
pp. 275-292
Author(s):  
Hasnaa Ali Ebrahim ◽  
Dalia Mahmoud Abdelmonem Elsherbini
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Caspase 3 ◽  
Histopathological Examination ◽  
Activity Index ◽  
Chronic Inflammatory Bowel Disease ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Colonic Tissue ◽  
Intestinal Epithelial Barrier

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with intestinal epithelial barrier impairment. Polydatin (PD), a natural product isolated from <i>Polygonum cuspidatum</i>, is known to have an anti-inflammatory, antioxidant, and antiapoptotic effect. We attempted to compare the protective impact of PD pretreatment on alterations to the intestinal epithelial barrier and the colonic wall’s ultrastructure accompanying ulcerative colitis to other conventional drugs in practice, primarily L-carnosine, which has not been addressed before. The rats were divided into 5 groups; 3 of them were treated with sulphasalazine (500 mg/kg), L-carnosine (30 mg/kg), and PD (45 mg/kg). All groups were administered their respective drugs 3 days before the UC was induced by acetic acid intra-rectally, and the treatment was continued until the 11th day. The disease activity index (DAI) was estimated, and a macroscopic scoring was established for the harvested colonic tissue. The tissues were extracted and processed for hematoxylin and eosin staining, caspase-3 immunohistochemical staining, electron microscopy, and biochemical analysis evaluating proinflammatory markers (IL-1β, TNF-α, and IL-6), myeloperoxidase (MPO), oxidative stress, and lipid peroxidation. Histopathological examination of colonic tissue showed that PD pretreatment effectively restored mucosal epithelial cells, intercellular tight junctions, goblet cells, and maintained the intestinal epithelial and endothelial barriers. PD suppressed MPO, proinflammatory markers, and malondialdehyde but enhanced superoxide dismutase and glutathione levels. It also hampered apoptosis, as evidenced by a reduction in caspase-3 expression. PD showed a significantly better response in preserving the intestinal epithelial barrier against acetic acid-induced colitis as compared to sulphasalazine and L-carnosine. These findings demonstrate the therapeutic role of PD for patients with UC.

scholarly journals Baitouweng Decoction Ameliorates Ulcerative Colitis in Mice Partially Attributed to Regulating Th17/Treg Balance and Restoring Intestinal Epithelial Barrier

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiwei Miao ◽  
Liping Chen ◽  
Hui Feng ◽  
Mingjia Gu ◽  
Jing Yan ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Intestinal Inflammation ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Treg Cells ◽  
Raw 264.7 Cells ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Colon Tissue

Ulcerative colitis (UC) is a chronic intestinal disease with unclear pathogenesis. With an increasing global prevalence over the past two decades, UC poses a serious threat to public health. Baitouweng decoction (BTW), a traditional Chinese medicine, has been shown to have good clinical efficacy for treating intestinal inflammation. Yet, the efficacy of BTW in UC and the underlying mechanism remain unclear. The current study aimed to determine whether BTW suppressed intestinal inflammation in mice and the potential mechanism. We used a dextran sulfate sodium (DSS)-induced murine colitis model to test the anti-inflammatory efficacy of BTW. Clinical symptoms were scored by the disease activity index (DAI), and the colon length and pathological changes in colon tissue were also used to further evaluate the efficacy of BTW. Precisely how BTW affected immune function and the intestinal barrier of UC mice was also examined. BTW significantly reduced DAI score and colonic pathological damage. BTW regulated the balance between T helper (Th)17 and regulatory T (Treg) cells, decreased interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, and increased IL-10 levels. BTW reduced intestinal permeability of UC mice, increased expression of tight junction proteins (occludin and zonula occludens-1), and decreased expression of phospho-nuclear factor (p-NF)-κB and phospho-extracellular signal-regulated kinase (p-ERK) in the colon. BTW inhibited the ERK/p-NF-κB signaling pathway and suppressed expression of cyclo-oxygenase-2 and inducible NO synthase in lipopolysaccharide-activated RAW 264.7 cells. BTW significantly promoted the synthesis of short-chain fatty acids in the gut, particularly acetate, propionate, isobutyric acid, and isovalerate. The results suggest that BTW can protect against DSS-induced UC. The mechanism may be partially attributed to regulating the balance of Th17/Treg cells and restoring the intestinal epithelial barrier.

scholarly journals Hsa_circ_0001021 regulates intestinal epithelial barrier function via sponging miR-224-5p in ulcerative colitis

Epigenomics ◽  
2021 ◽  
Author(s):  
Bing Li ◽  
Yan Li ◽  
Lixiang Li ◽  
Yu Yu ◽  
Xiang Gu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Functional Analysis ◽  
Barrier Function ◽  
Colonic Mucosa ◽  
Clinical Samples ◽  
Epithelial Barrier ◽  
Healthy Controls ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

Aims: Few circRNAs have been thoroughly explored in ulcerative colitis (UC). Materials & methods: Microarrays and qualitative real-time PCR were used to detect and confirm dysregulated circRNAs associated with UC. Functional analysis was performed to explore the roles. Results: A total of 580 circRNAs and 87 miRNAs were simultaneously dysregulated in both inflamed and noninflamed UC colonic mucosa compared with healthy controls. Accordingly, hsa_circ_0001021 was significantly downregulated in patients with UC and was related to Mayo scores. Clinical samples and cell experiments revealed that hsa_circ_0001021 was expressed in epithelial cells and correlated with ZO-1, occludin and CLDN-2. Moreover, hsa_circ_0001021 sponged miR-224-5p to upregulate smad4 and increased ZO-1 and occludin. Conclusion: Hsa_circ_0001021 is related to UC severity and regulates epithelial barrier function via sponging miR-224-5p.

scholarly journals miR-24 Is Elevated in Ulcerative Colitis Patients and Regulates Intestinal Epithelial Barrier Function

2019 ◽  
Vol 189 (9) ◽  
pp. 1763-1774 ◽  
Author(s):  
Artin Soroosh ◽  
Carl R. Rankin ◽  
Christos Polytarchou ◽  
Zulfiqar A. Lokhandwala ◽  
Ami Patel ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

2016 ◽  
Vol 310 (11) ◽  
pp. G1118-G1123 ◽  
Author(s):  
Michael Meir ◽  
Sven Flemming ◽  
Natalie Burkard ◽  
Johanna Wagner ◽  
Christoph-Thomas Germer ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Intestinal Barrier ◽  
Chronic Inflammatory Bowel Disease ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Health And Disease ◽  
Inflammatory Bowel

Regulation of the intestinal epithelial barrier is a differentiated process, which is profoundly deranged in inflammatory bowel diseases. Recent data provide evidence that the glial cell line-derived neurotrophic factor (GDNF) is critically involved in intestinal epithelial wound healing and barrier maturation and exerts antiapoptotic effects under certain conditions. Furthermore, not only the enteric nervous system, but also enterocytes synthesize GDNF in significant amounts, which points to a potential para- or autocrine signaling loop between enterocytes. Apart from direct effects of GDNF on enterocytes, an immunomodulatory role of this protein has been previously assumed because of a significant reduction of inflammation in a model of chronic inflammatory bowel disease after application of GDNF. In this review we summarize the current knowledge of GDNF on intestinal epithelial barrier regulation and discuss the novel role for GDNF as a regulator of intestinal barrier functions in health and disease.

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 Olmesartan modulates proliferating cell nuclear antigen expression and improves dextran sulfate: induced ulcerative colitis in rats

2021 ◽  
Vol 10 (3) ◽  
pp. 209
Author(s):  
Hanan Tawfeek Emam ◽  
Amany N. Ibrahim
Keyword(s):  
Ulcerative Colitis ◽  
Histopathological Examination ◽  
Treated Group ◽  
Nuclear Antigen ◽  
Chronic Inflammatory Bowel Disease ◽  
Therapeutic Drug ◽  
Control Group ◽  
Albino Rats ◽  
Colonic Tissue ◽  
Bax Protein

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by sudden attacks of remissions and exacerbations with increased incidence of cancer colon. The present study aims to determine the possible ameliorative mechanisms of Olmesartan in UC induced experimentally in rat.Methods: Adult albino rats were randomly grouped into control, UC model non treated group: Rats received dextran sodium (DSS) orally for 21 days with intra-colic administration of acetic acid (AA) for 3 consecutive days for induction of UC model, Olmesartan (1, 5, 10mg/kg/orally) and UC + Olmesartan in different doses (1 mg, 5 mg and 10 mg/kg/day orally).Results: DSS orally and AA intra-rectal produced sever colitis manifested by significant weight loss, watery and bloody diarrhea. Significant increase in serum and colonic tissue levels of tumor necrosis factor alpha and interleukine-1β. Pro-apoptotic Bax protein, myeloperoxidase (MPO) and expression of PCNA significantly increased in colonic tissue. Lipid peroxidation (MDA) significantly elevated while reduced glutathione (GSH) was depleted in UC non-treated group compared with normal control group. Treatment with Olmesartan (5 mg, 10 mg/kg/day, orally) ameliorated mucosal ulceration and improved inflammatory signs as confirmed by immunohistochemical and histopathological examination. Also, Olmesartan significantly attenuates overexpression of PCNA in colonic mucosa.Conclusions: Our results point out that Olmesartan had ameliorative effects on UC by its anti-inflammatory, antioxidant and anti-apoptotic effects and attenuates PCNA expression which is the main cause of dysplasia and colorectal cancer. Olmesartan may be a promising therapeutic drug for treating UC and protection of colorectal carcinoma.  

Sign in / Sign up

Export Citation Format

Share Document