Ameliorative Effect of Sinapic Acid on Dextran Sodium Sulfate- (DSS-) Induced Ulcerative Colitis in Kunming (KM) Mice

Ulcerative colitis is a chronic gastrointestinal disease characterized by intestinal inflammation and serious mucosal damage. As a naturally hydroxycinnamic acid, sinapic acid (SA) has antioxidant, anticancer, and neuroprotective activities. We investigated the anticolitic effect and potential mechanisms of SA in DSS-induced colitis in Kunming (KM) mice. SA treatment significantly reduced body weight loss, colon shortening, and intestinal wall thickening in colitis mice. SA treatment also significantly reduced the histological infiltration of inflammatory cells and decreased myeloperoxidase (MPO) activity in the colons of colitis mice. The administration of SA attenuated oxidative damage by enhancing the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase and reduced the serum and colonic mRNA levels of proinflammatory cytokines in colitis mice. We used qRT-PCR and Western blotting assays and demonstrated that SA reduced the activation of the NLRP3 inflammasome and attenuated intestinal permeability by enhancing the expression of ZO-1, occludin, and claudin-1 in colitis mice. Here, we conclude that SA exhibits great anticolitic activity against DSS-induced colitis by enhancing the activity of antioxidant enzymes, reducing intestinal inflammation, and maintaining the intestinal barrier. Finally, we suggest that SA may be a safe adjuvant for the prevention of clinical colitis.

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Challenge in diagnosis of late onset necrotizing enterocolitis in a term infant: a case report

BMC Pediatrics ◽

10.1186/s12887-021-02626-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gunadi ◽

Dian Nirmala Sirait ◽

Aditya Rifqi Fauzi ◽

Ninditya Nugroho ◽

Fadil Fahri ◽

...

Keyword(s):

Ct Scan ◽

Necrotizing Enterocolitis ◽

Intestinal Inflammation ◽

Late Onset ◽

Gastrointestinal Disease ◽

Early Recognition ◽

Ileocecal Valve ◽

Abdominal Distention ◽

Clinical Deterioration ◽

Wall Thickening

Abstract Background Necrotizing enterocolitis (NEC) is a common devastating inflammatory gastrointestinal disease and frequently occurs in premature infants. Here, we reported a case of late-onset NEC in a term neonate with good outcome after surgery for long-term follow-up. Case presentation Ten-week-old male came to emergency unit due to prolonged diarrhea and abdominal distention. He was born at gestational age of 40 weeks with birth weight and Apgar score of 2800 g and 7/8, respectively. He had no history of formula feeding. Two weeks before admitted to the hospital, the patient had frequent diarrhea with fever. He was found lethargic with abdominal distention, absence of bowel sounds and abdominal tenderness. Plain abdominal x-ray and CT scan showed gastric and intestinal dilatation and gasless colon, suggesting a small bowel obstruction, and bowel wall thickening indicating peritonitis, without any free subdiaphragmatic air (pneumoperitoneum). Moreover, the patient did not have a congenital heart disease. While in intensive medical treatment, he showed a continuous clinical deterioration. All findings were suggestive of intestinal inflammation with clinical deterioration, and we decided to perform an emergency exploratory laparotomy and found an ischemia along the jejunoileal with a perforation at 25 cm above the ileocecal valve. Subsequently, we performed a double-barrel ileostomy through a separate incision from the laparotomy. Histopathological findings confirmed the diagnosis of NEC. We closed the stoma at postoperative day 43. The patient was discharged uneventfully a month after stoma closure. Conclusion Abdominal CT scan might be useful to establish an early recognition of late-onset NEC; thus, immediate surgical intervention might be performed to decrease its morbidity and mortality. Moreover, late-onset NEC in term neonates might occur without any risk factors or significant co-morbidities.

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Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽

10.1055/a-1506-3476 ◽

2021 ◽

Author(s):

Jiaqi Wu ◽

Yuzheng Wu ◽

Yue Chen ◽

Mengyang Liu ◽

Haiyang Yu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Activity Index ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Function Evaluation ◽

Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

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Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1809575115 ◽

2018 ◽

Vol 115 (43) ◽

pp. 11036-11041 ◽

Cited By ~ 12

Author(s):

Yasuharu Nagahama ◽

Mayuko Shimoda ◽

Guoliang Mao ◽

Shailendra Kumar Singh ◽

Yuuki Kozakai ◽

...

Keyword(s):

Acute Inflammation ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Body Weight Loss ◽

Purine Metabolism ◽

Intestinal Epithelial ◽

Beneficial Effects ◽

Epithelial Regeneration ◽

Mtorc1 Signaling ◽

Inflammatory Bowel

Damage to intestinal epithelial cell (IEC) layers during intestinal inflammation is associated with inflammatory bowel disease. Here we show that the endoribonuclease Regnase-1 controls colon epithelial regeneration by regulating protein kinase mTOR (the mechanistic target of rapamycin kinase) and purine metabolism. During dextran sulfate sodium-induced intestinal epithelial injury and acute colitis, Regnase-1∆IEC mice, which lack Regnase-1 specifically in the intestinal epithelium, were resistant to body weight loss, maintained an intact intestinal barrier, and showed increased cell proliferation and decreased epithelial apoptosis. Chronic colitis and tumor progression were also attenuated in Regnase-1∆IEC mice. Regnase-1 predominantly regulates mTORC1 signaling. Metabolic analysis revealed that Regnase-1 participates in purine metabolism and energy metabolism during inflammation. Furthermore, increased expression of ectonucleotidases contributed to the resolution of acute inflammation in Regnase-1∆IEC mice. These findings provide evidence that Regnase-1 deficiency has beneficial effects on the prevention and/or blocking of intestinal inflammatory disorders.

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Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1522193112 ◽

2015 ◽

Vol 113 (1) ◽

pp. E7-E15 ◽

Cited By ~ 355

Author(s):

Hyun Jung Kim ◽

Hu Li ◽

James J. Collins ◽

Donald E. Ingber

Keyword(s):

Epithelial Cells ◽

Pathogenic Bacteria ◽

Intestinal Inflammation ◽

Bacterial Overgrowth ◽

Intestinal Barrier ◽

Inflammatory Cells ◽

Intestinal Barrier Function ◽

Human Gut ◽

Intestinal Bacterial Overgrowth

A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.

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Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils

Frontiers in Immunology ◽

10.3389/fimmu.2021.760999 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jie Ren ◽

Dong Yan ◽

Yichun Wang ◽

Jiaojiao Zhang ◽

Min Li ◽

...

Keyword(s):

Ulcerative Colitis ◽

Intestinal Barrier ◽

Protein Supplementation ◽

Signalling Pathway ◽

Mrna Levels ◽

Disease Symptoms ◽

E Coli ◽

Tnf Α ◽

Dithiocarbamic Acid ◽

Potential Strategy

The loss of inhibitor of differentiation-2 (ID2) could lead to the development of colitis in mice, supplementation with exogenous ID2 protein might be a potential strategy to ameliorate colitis. In this study, the effects of ID2 protein supplementation on Dextran sodium sulfate (DSS)-induced colitis were investigated. Firstly, we confirmed that the expression of ID2 was reduced in the colon tissues of DSS-induced colitis mice and patients with ulcerative colitis (UC). Then, we constructed a recombinant plasmid containing the human Id2 gene and expressed it in Escherichia coli (E. coli) successfully. After purification and identification, purified hID2 could ameliorate DSS-induced colitis efficiently in mice by improving disease symptoms, decreasing the levels of proinflammatory cytokines in colon tissues, maintaining the integrity of intestinal barrier and reducing the infiltration of neutrophils and macrophages in the colon. Further study showed that hID2 could be endocytosed efficiently by neutrophils and macrophages, and hID2 lost its protection function against colitis when neutrophils were depleted with an anti-Gr-1 antibody. hID2 decreased the mRNA levels of IL-6, IL-1β and TNF-α in lipopolysaccharides (LPS)-stimulated neutrophils and efficiently inhibited the activation of NF-κB signalling pathway in neutrophils. Interestingly, hID2 showed a synergistic role in inhibition of NF-κB activation with pyrrolidine dithiocarbamic acid (PDTC), an inhibitor of NF-κB activation. Therefore, this study demonstrated the potential use of hID2 to treat UC, and hID2 protein might be a promising anti-inflammatory agent that targets the NF-κB signalling pathway in neutrophils.

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Intestinal barrier breakdown and mucosal microbiota disturbance in neuromyelitis optical spectrum disorder

10.21203/rs.3.rs-22503/v1 ◽

2020 ◽

Author(s):

Chunping Cui ◽

Sha Tan ◽

Li Tao ◽

Junli Gong ◽

Yanyu Chang ◽

...

Keyword(s):

Intestinal Inflammation ◽

Water Channel ◽

Intestinal Barrier ◽

Inflammatory Cells ◽

Amplicon Sequencing ◽

Spectrum Disorder ◽

Pathophysiological Mechanism ◽

Intestinal Dysbiosis ◽

Barrier Breakdown ◽

Junction Proteins

Abstract Background and purpose The mechanism underlying the pathology of neuromyelitis optica spectrum disorder (NMOSD) remains unclear even though increased expression of the water channel protein aquaporin-4 (AQP4) on astrocytes plays an important role. Our previous study revealed that dysbiosis was detected in the faecal microbiota of NMOSD patients. In this study, we further investigated whether the intestinal barrier and mucosal flora balance were also interrupted in NMOSD patients. Methods Sigmoid mucosal biopsies were collected via endoscopy from six patients with NMOSD and compared with those from three patients with multiple sclerosis (MS) and five healthy controls (HCs). These samples were processed for electron microscopy and immunohistochemistry to investigate changes in ultrastructure and in the number and size of intestinal inflammatory cells. Changes in mucosal flora were also analysed by high-throughput 16S ribosomal RNA gene amplicon sequencing. Results The intercellular space between epithelia of the colonic mucosa became wider in MS and NMOSD patients compared to the HCs (P < 0.01), and the expression of tight junction proteins in MS and NMOSD patients significantly decreased compared to that in the HCs. Activation of microphages with many inclusions inside the cytoplasm and enlarged plasmocytes with more particles were found in the NMOSD group. Quantitative analysis showed that the percentage of small-size CD 38 + and CD138 + cells was lower but that of larger-size cells became higher in NMOSD patients, and 16S data showed that the abundance of Streptococcus and Granulicatella was dramatically increased in NMOSD patients. Conclusions NMOSD patients exhibited a disrupted intestinal barrier and intestinal dysbiosis and activation of intestinal inflammation, which suggested a potential pathophysiological mechanism of NMOSD underlying intestinal inflammation.

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Efficacy of quercetin derivatives in prevention of ulcerative colitis in rats

Interdisciplinary Toxicology ◽

10.2478/intox-2013-0002 ◽

2013 ◽

Vol 6 (1) ◽

pp. 9-12 ◽

Cited By ~ 18

Author(s):

Ruzena Sotnikova ◽

Viera Nosalova ◽

Jana Navarova

Keyword(s):

Ulcerative Colitis ◽

Acetic Acid ◽

Intestinal Inflammation ◽

Tissue Injury ◽

Reductase Activity ◽

Antioxidant Properties ◽

Control Group ◽

Wall Thickening ◽

Quercetin Derivatives

Abstract Reactive oxygen species has been implicated to contribute significantly to tissue injury associated with ulcerative colitis. Thus compounds with antioxidant properties could be potential therapeutic agents in this disease. Flavonoid compounds are known to possess antioxidative and antiinflammatory properties. Two derivatives of the flavonoid quercetin (Q), chloronaphthoquinone quercetin (CNC) and monochloropivaloyl quercetin (MCP), showed improved antioxidant properties and moreover, they efficiently inhibited aldose reductase activity in vitro. The aim of the work was to test the potential efficacy of quercetin and these synthetic derivatives in vivo in prevention of intestinal inflammation during ulcerative colitis in rats. Colitis was induced by intracolonic administration of acetic acid (4% solution). The control group received the same volume of saline. The vehicle dimethyl sulfoxide (DMSO) and the drugs Q, CNC or MCP were administered orally two hours and then one hour before the acetic acid or saline instillation. After 48 hours, the animals were sacrificed and the colon was weighed, measured and scored for visible damage. Acetic acid triggered an intense inflammatory response of the colon, characterised by haemorrhage, ulceration and bowel wall thickening. From the drugs tested, only CNC (2 × 50 mg/kg) effectively depressed inflammatory damage of the colon. The mechanism of this beneficial effect remains to be elucidated.

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Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00140.2004 ◽

2005 ◽

Vol 288 (4) ◽

pp. G621-G629 ◽

Cited By ~ 56

Author(s):

Paola Brun ◽

Cristina Mastrotto ◽

Elisa Beggiao ◽

Annalisa Stefani ◽

Luisa Barzon ◽

...

Keyword(s):

Weight Loss ◽

Wound Healing ◽

Body Weight ◽

Intestinal Inflammation ◽

Body Weight Loss ◽

Myeloperoxidase Activity ◽

Mrna Levels ◽

Cox 2 ◽

Chronic Intestinal Inflammation

Because neurotensin (NT) and its high-affinity receptor (NTR1) modulate immune responses, chloride secretion, and epithelial cell proliferation, we sought to investigate their role in the repair process that follows the development of mucosal injuries during a persistent inflammation. Colonic NT and NTR1, mRNA, and protein significantly increased only after dextran sodium sulfate (DSS)-induced inflammatory damage developed. Colitis-induced body weight loss, colonic myeloperoxidase activity, and histological damage were significantly enhanced by SR-48642 administration, a nonpeptide NTR1 antagonist, whereas continuous NT infusion ameliorated colitis outcome. To evaluate the NT and NTR1 role in tissue healing, mucosal inflammatory injury was established administering 3% DSS for 5 days. After DSS discontinuation, mice rapidly gained weight, ulcers were healed, and colonic NT, NTR1, and cyclooxygenase (COX)-2 mRNA levels were upregulated, whereas SR-48642 treatment caused a further body weight loss, ulcer enlargement, and a blunted colonic COX-2 mRNA upregulation. In a wound-healing model in vitro, NT-induced cell migration in the denuded area was inhibited by indomethacin but not by an antitransforming growth factor-β neutralizing antibody. Furthermore, NT significantly increased COX-2 mRNA levels by 2.4-fold and stimulated PGE2 release in HT-29 cells. These findings suggest that NT and NTR1 are part of the network activated after mucosal injuries and that NT stimulates epithelial restitution at least, in part, through a COX-2 dependent pathway.

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Effect of Extracellular Vesicles Derived From Lactobacillus plantarum Q7 on Gut Microbiota and Ulcerative Colitis in Mice

Frontiers in Immunology ◽

10.3389/fimmu.2021.777147 ◽

2021 ◽

Vol 12 ◽

Author(s):

Haining Hao ◽

Xinyi Zhang ◽

Lingjun Tong ◽

Qiqi Liu ◽

Xi Liang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Lactobacillus Plantarum ◽

Extracellular Vesicles ◽

Intestinal Inflammation ◽

Body Weight Loss ◽

Tnf Α ◽

Cytokine Levels ◽

Anti Inflammatory ◽

Inflammatory Effect

Probiotics plays an important role in regulating gut microbiota and maintaining intestinal homeostasis. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect. However, the anti-inflammatory effect and mechanism of probiotics derived EVs on inflammatory bowel disease (IBD) remains unclear. In this study, the effect of Lactobacillus plantarum Q7-derived extracellular vesicles (Q7-EVs) on gut microbiota and intestinal inflammation was investigated in C57BL/6J mice. The results showed that Q7-EVs alleviated DSS-induced colitis symptoms, including colon shortening, bleeding, and body weight loss. Consumption of Q7-EVs reduced the degree of histological damage. DSS-upregulated proinflammatory cytokine levels including IL-6, IL-1β, IL-2 and TNF-α were reduced significantly by Q7-EVs (p < 0.05). 16S rRNA sequencing results showed that Q7-EVs improved the dysregulation of gut microbiota and promoted the diversity of gut microbiota. It was observed that the pro-inflammatory bacteria (Proteobacteria) were reduced and the anti-inflammatory bacteria (Bifidobacteria and Muribaculaceae) were increased. These findings indicated that Q7-EVs might alleviate DSS-induced ulcerative colitis by regulating the gut microbiota.

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Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.665376 ◽

2021 ◽

Vol 12 ◽

Author(s):

Linghang Qu ◽

Xiong Lin ◽

Chunlian Liu ◽

Chang Ke ◽

Zhongshi Zhou ◽

...

Keyword(s):

Ulcerative Colitis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Mapk Pathway ◽

Activity Index ◽

Intestinal Barrier ◽

Disease Activity Index ◽

Inflammatory Factors ◽

Therapeutic Effects

In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.

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