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Objective: To investigate the effect of oligosaccharide grape seed proanthocyanins (GSPE) on dextran sulphate sodium salt (DSS)-induced ulcerative colitis (UC) in mice and its mechanisms. Methods: SPF-class C57 mice were randomly divided into normal group, model group, positive group (sulfasalazine group), and GSPE groups (125, 250, 500 mg/kg). The normal group was given pure water, and the other groups were free to drink 3% DSS aqueous solution for 7 d to induce the model of UC in mice. The changes of body weight, hematochezia and stool type were recorded every day. After seven days of treatment, blood, colons and spleens were collected, and the length of the colon and the weight of the spleen were recorded. HE staining was used to evaluate the pathological changes of colonic mucosa in mice. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor TNF-α in serum and colon tissues and the levels of NO, MDA, and SOD were detected by ELISA. The changes of HO-1, NF-κB, and Nrf2 in colonic epithelial cells were analyzed by immunohistochemistry. Results: Compared with the model group, the body weight of mice in GSPE groups (250, 500 mg/kg) decreased relatively slowly, and the symptoms of diarrhea and hematochezia were improved significantly. The content of IL-1β, IL-6, TNF-α, NO, and MDA in serum and colon tissues was much lower in the administration groups than those in the model group, while the content of SOD was significantly higher (P < 0.01). The pathological tissue analysis showed that the pathological damage of colonic mucosa in the high dose group of GSPE was obviously decreased. Immunohistochemical analysis showed that GSPE groups significantly decreased the expression of NF-κB and increased the expression of Nrf2 and HO-1 (P < 0.01). Conclusion: GSPE could effectively improve the symptoms of UC induced by DSS, and regulate the expression of oxidative stress-related proteins Nrf2, HO-1 and inflammatory pathway protein NF-κB, and then affect the changes of oxidative stress indicators SOD, MDA and inflammatory factors. Therefore, GSPE plays an important role in the treatment and prevention of UC.
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BACKGROUND: Crocin has anti-inflammatory and anti-oxidative stress effects. The therapeutic effects of crocin on ulcerative colitis and related mechanisms are still unclear. OBJECTIVE: To explore the protective effect of crocin in ulcerative colitis rats and its related mechanism. METHODS: Thirty Sprague-Dawley rats were randomly divided into five groups: normal group, model group, low-dose crocin group, high-dose crocin group, and positive control group. Experimental rat model of ulcerative colitis was induced by dextran sodium sulfate. Starting on the first day of modeling, rats were routinely fed in the normal group, were given sulfasalazine by gavage in the positive drug group, and were gavaged with 0.05 and 0.1 g/kg crocin in the low-and high-dose crocin groups, respectively. RESULTS AND CONCLUSION: One week after intervention, the crocin-treated rats had significantly decreased scores on colon tissue injury and Crohn’s disease activity index(P < 0.05). Compared with the model group, crocin groups had a decrease in the content of malondialdehyde and activity of myeloperoxidase(P < 0.05), and an increase in the activity of superoxide dismutase in the colon tissue(P < 0.05). Shown by immunohistochemical staining, compared with the model group, treatment with crocin significantly reduced immune responses of tumor necrosis factor α and interleukin 23 proteins after 1 week of intervention(P < 0.05). Compared with the model group, treatment with crocin downregulated the expression levels of total protein Bax, Caspase-3, Toll-like receptor 4 and MyD88(P < 0.05), and upregulated the expression of Bcl-2 in the intestinal tissue of rats(P < 0.05). These results indicate that crocin has a certain therapeutic effect in ulcerative colitis rats and its mechanism may be related to down-regulation of the Toll-like receptor 4/MyD88 signaling pathway and inhibition of oxidative stress, inflammation and apoptosis in the colon.
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AIM: To observe the effect of Tripterygium glycosides on NOXs-ROS-NLRP3 inflammatory signa-ling pathways in the colon tissue in dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mice, and to investi-gate the underlying mechanisms.METHODS: BALB/c mice were used and the mouse model of UC was established by DSS induction.The mice were randomly divided into 5 groups (model group, low-, medium-and high-dose Tripterygium glycosides groups, and normal group).The colon tissues were collected 21 d after Tripterygium glycosides gavage.The mRNA expression of NLRP3, ASC and caspase-1 in the colon tissues was detected by real-time PCR.The caspase-1 ex-pression in the colorectal mucosa was observed by immunohistochemical method.ELISA was used to detect the protein le- vels of IL-1α, TNF-αand IL-13.The production of reactive oxygen species (ROS) was measured by chemiluminescence technique, and the consumption rate of NADPH, which was inhibited by DPI, was analyzed to determine the activity of NADPH oxidases (NOXs).The neutrophils were isolated, and the ROS production, NOXs activity, and the mRNA ex-pression of NLRP3, ASC and caspase-1 were also detected.RESULTS: The colon tissues were abnormal with different de-grees in Tripterygium glycosides groups, and histopathological scores were lower than that in model group.In Tripterygium glycosides groups, in addition to the mRNA expression levels of caspase-1 in the colon tissues between normal group and high-dose group, ROS production, NOXs activity and the mRNA expression levels of NLRP3, ASC and caspase-1 in the colon tissues and colon-isolated neutrophils were lower than those in model group (P <0.05), and higher than those in normal group (P <0.05).The results of pairwise comparison for the efficacy of Tripterygium glycosides administration showed that the above indexes were statistically significant except the mRNA expression levels of caspase-1 between middle-dose group and high-dose group.Tripterygium glycosides administration significantly decreased the expression levels of proinflammatory cytokines IL-1αand TNF-αin the homogenates of colon tissues in the model mice (P <0.05).No differ-ence of IL-13 expression among the groups was observed.CONCLUSION: Tripterygium glycosides inhibits NOXs-ROS-NLRP3 inflammatory signaling pathways to reduce the expression of IL-1α, TNF-αand other proinflammatory cytokines, and attenuates DSS-induced ulcerative colitis in mice, by which the neutrophils might be involved in the process.
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Aims: Ulcerative colitis (UC) is considered as an idiopathic, chronic inflammatory bowel disease (IBD) with multifactorial agents. Tumor necrosis factor-alpha (TNF-α) has been suggested to be one of them. The study was designed to evaluate whether pentoxifylline (PTX), as TNF-α suppressor, has a beneficial effect in rats with dextran sulfate sodium (DSS) induced-colitis. Study Design: Original research papers. Place and Duration of Study: In both Anatomy Department, Faculty of Medicine, Menoufia University and Animal medicine & Infectious Diseases Department, Faculty of Veterinary Medicine Sadat City Branch , Menoufia University, Egypt , between April 2009 and August 2010. Methodology: Fifty adult male rats were divided randomly and equally into: control group, model control group, colitis model group, PTX treated group and recovery group. Induction of colitis was made in colitis model by adding DSS to the drinking water; for three weeks (5% for one week followed by 3% of for two weeks). Rats in both PTX treated and model control groups received pentoxifylline for two weeks after the induction of colitis; by intraperitoneal injection (100 mg/kg/day; 1ml /rat). Colon mucosal inflammation and damage were assessed through; clinical, macroscopic, microscopic, morphometric and molecular assessments. Results: Rats treated with oral administration of DSS for three weeks developed clinical and macroscopic signs of colitis. Treatment with PTX for two weeks, in the treated group or cessation of DSS for two weeks, in the recovery group relieved the colitis symptoms including: diarrhea, reduction in body weight, shortening and ulceration of the colon and extensive colonic damage. All of these were associated with a significant increase in TNF-α m RNA expression. However, an improvement was more significant among treated animals than that in the recovery one. Conclusion: Pentoxyfylline seems to be an effective in the treatment of ulcerative colitis for further investigation. Also, the unclear dual role of mast cell in both induction and treatment of the disease should be considered in a further investigation.
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Objective To investigate the effects of aloperine (ALO) on a model of dextran sulphate sodium (DSS)-induced chronic colitis in C57BL/6 mice.Methods Repeated colitis was induced by administration of four cycles of 4％ DSS.The severity of colitis was assessed on the basis of clinical signs,ratio of colon weight and colon length,and histological grading scores.Moreover,secretory immunoglobulin A (S-IgA) and plasma haptoglobin (HP) were analyzed by enzyme-linked immunosorbent assay,and the changes of mRNA expression of ICAM-1and MIF gene in colorectal tissue were detected by quantitative reverse transcriptase real-time polymerase chain reaction using SYBR Green Ⅰ.Results ALO administration significantly attenuated the colon damage,caused substantial reductions of the rise in HP,and maintained the level of cecum S-IgA.ALO inhibited the ICAM-1mRNA expression and had no effect on MIF mRNA expression.Conclusion The effect of ALO on DSS-induced chronic colitis in mice is investigated for the first time,which suggests that ALO could be an attractive therapeutic candidate in the treatment of inflammatory bowel disease.
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Objective To evaluate the preventive and therapeutic effects of heparin on dextron sulphate sodium (DSS)-induced colitis in mice. Methods The normal mice (n=16) which had been received DSS orally for 7 days were randomized into two groups, the preventive group with heparin subcutaneous administration, and the control group with normal saline subcutaneous administration. The DSS-induced colitis mice (n=16) were randomized into two groups, the treatment group with heparin and the control group with normal saline subcutaneous injection for 7 days. The preventive and therapeutic effects of heparin were assessed by disease activity index (DAI), histological score, TNF-? mRNA expression using hybridization in situ, and Martius scarlet blue (MSB) fibrin staining used to identify microvascular thrombi. Results Microvascular thrombi in the prevention group significantly decreased compared with those in the controls. Microvascular thrombi were positive in 4 of 8 controls, none in the prevention group (P=0.038). Histological score and TNF-? mRNA in the treatment group significantly decreased compared with those in the controls. Histological score of rectum and transverse colon, and expression of TNF-? mRNA in the treatment group and those in the controls were 1.33 and 1.85(P