scholarly journals Improvement of Oxazolone-Induced Ulcerative Colitis in Rats Using Andrographolide

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 76 ◽  
Author(s):  
Liuhong Zhang ◽  
Ning Cao ◽  
Yuwen Wang ◽  
Youxu Wang ◽  
Chao Wu ◽  
...  

Ulcerative colitis (UC) is usually accompanied with symptoms of abdominal pain, diarrhea, and bloody stool, which impair the quality of life of patients. Previous studies have shown that Andrographis paniculata extracts, which have andrographolide (AND) as their main compound, can relieve UC symptoms in patients. The aim of the study was to investigate the alleviating effect of AND on UC using the oxazolone (OXZ)-induced UC rat model. A total of 66 healthy male Sprague Dawley rats were used to evaluate the efficacy and mechanism of AND on UC (n = 11 per group) and grouped into control, model, SASP (sulfasalazine, positive control group, 500 mg/kg), AND-L (40 mg/kg), AND-M (80 mg/kg), and AND-H (120 mg/kg). The colonic disease activity index (DAI), colon length, spleen coefficient, pathological damage, and inflammation-related cytokine and protein expression levels were used as indices for evaluation. Results showed that the AND groups had reduced DAI and mortality, and significantly improved colon length and spleen coefficient compared with the model group. Furthermore, OXZ-induced histological injury was relieved significantly after AND treatment due to an improved crypt structure and reduced infiltration of inflammatory cells. Moreover, AND inhibited myeloperoxidase (MPO) activity and the secretion of interleukin-4 (IL-4), IL-13, and tumor necrosis factor α (TNF-α). The results of the anti-inflammatory mechanism revealed that AND blocked the signal transduction by reducing IL-4/IL-13 specific binding to IL-4 receptor (IL-4R) and inhibiting the phosphorylation of the signal transducer and activator of transcription 6 (p-STAT6). In conclusion, aside from natural plants, AND may be a candidate ingredient for UC therapy.

2014 ◽  
Vol 51 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Luiz Gustavo de OLIVEIRA ◽  
André Luiz da CUNHA ◽  
Amaury Caiafa DUARTE ◽  
Maria Christina Marques Nogueira CASTAÑON ◽  
Júlio Maria Fonseca CHEBLI ◽  
...  

ContextInflammatory bowel disease, including ulcerative colitis and Crohn’s disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases.ObjectivesEvaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium.MethodsColitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined.ResultsDextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group.ConclusionsIn this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.


2015 ◽  
Vol 65 (3) ◽  
pp. 339-347
Author(s):  
Hijová Emília ◽  
Śoltésová Alena ◽  
Salaj Rastislav ◽  
Kuzma Jozef ◽  
Strojný Ladislav ◽  
...  

Abstract The aim of this study was to investigate the influence of prebiotic inulin diet intervention on the activity of β-glucuronidase and counts of coliforms and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8) and transcription nuclear factor kappa beta (NFkB) activities in the colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. Male Sprague-Dawley rats (8 per group) were randomly divided into three groups: Control, Acute colitis and Prebiotic. Colitis was induced using 5% DSS in drinking water for 7d. DSS application significantly increased the activity of β-glucuronidase (p<0.001), increased counts of coliform bacteria and decreased lactobacilli count (p<0.05) in comparison to the control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFkB activities showed an increased expression in the acute colitis group. These results correspond to the average value of the disease activity index score (DAI) and revealed the maximum DAI score (6.5) in the acute colitis group. A decrease in the DAI score (4.13) was observed after application of the prebiotic inulin. Inulin diet intervention positively modified the number of microorganims and decreased β-glucuronidase activity. Colon tissue activities of NFkB were significantly suppressed (p<0.001). The synthesis of proinflammatory cytokines IL-6 (p<0.01) in the serum and in the colon tissue, as well as tissue IL-8 (p<0.05) in the prebiotic group were downregulated. These findings indicate that the dietary intake of inulin suppressed the expression of the observed markers, which play an important role in the inflammatory process, which predisposes to the use of inulin in the prevention or treatment of acute colitis in human and veterinary medicine.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xi-Ying Li ◽  
Yan-Ting Yang ◽  
Yue Zhao ◽  
Xie-He Kong ◽  
Guang Yang ◽  
...  

Background. Moxibustion has been recognized as an effective approach for ulcerative colitis, yet its mechanism is not clear. The research aimed to investigate the influence of moxibustion on the activation of NLRP3 inflammasome and its mechanism in treating ulcerative colitis by observing miR7/RNF183 inducing IκB α ubiquitination to regulate NF-κB signaling pathway in an ulcerative colitis rat model. Methods. An ulcerative colitis rat model was established by unlimited access to self-administration of 3.5% (w/v) dextran sulfate sodium solution. Mild moxibustion was applied to bilateral Tianshu points (ST25) in the moxa-stick moxibustion group; rats in the control group were intervened by intraperitoneal injection of ubiquitination inhibitor, MG132. The disease activity index was determined at the end of the intervention; colon injury was observed and scored after hematoxylin-eosin staining; the immunohistochemical method was adopted to detect the expressions of colonic IL-1β and NLRP3 proteins; Western blot determined the expressions of RNF183, IκB α, and NF-κB p65 proteins in the colon; the immunofluorescence test was used to observe the coexpression of IκB α/ubiquitin and IκB α/RNF183 proteins in the colon; immunoprecipitation assay was adopted to observe the interaction between IκB α and RNF183 proteins; and quantitative real-time polymerase chain reaction determined the expression of colonic miR7. Results. Moxibustion lowered the disease activity index, manifesting as restored colonic tissue and reduced inflammatory reaction, and decreased expression levels of NLRP3 and IL-1β proteins, compared with the model group. It also reduced colonic expression of NF-κB p65 protein, together with the increased level of IκB α protein and weaker expression levels of ubiquitin and RNF183 proteins and mRNAs and stronger expression of miR7. There were no significant differences between the moxa-stick moxibustion group and the control group except the expressions of RNF183 protein and mRNA and miR7. Conclusion. Moxibustion encourages the recovery of colon injury probably by regulating the expression of NLRP3 protein in ulcerative colitis rats through miR7/RNF183/NF-κB signaling pathway.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Baohai Liu ◽  
Xuehua Piao ◽  
Lianyi Guo ◽  
Guijun Wang ◽  
Weihua Sun ◽  
...  

Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon. Current medical treatment of UC relies predominantly on the use of traditional drugs, including aminosalicylates, corticosteroids, and immunosuppressants, which failed to effectively control this disease’s progression and produced various side effects. Here, we report a new Chinese medicine intestine formula (CIF) which greatly improved the effect of mesalazine, an aminosalicylate, on UC. In the present study, 60 patients with chronic UC were treated with oral mesalazine alone or in combination with CIF enema. The combination of mesalazine and CIF greatly and significantly improved the clinical symptoms and colon mucosal condition and improved the Mayo Clinic Disease Activity Index and health-related quality of life, when compared to mesalazine alone. In particular, the addition of CIF further decreased serum levels of tumor necrosis factor-alpha and hypersensitivity C-reactive protein but in contrast increased interleukin-4. Thus, the results demonstrate the beneficial role of CIF in UC treatment, which may be mediated by the regulation of inflammation.


2021 ◽  
Vol 20 (10) ◽  
pp. 2213-2218
Author(s):  
Lina Wei ◽  
Hua Xu

Purpose: To determine the curative impact of mesalazine (MSZ)-BTVCs combination on ulcerative colitis (UC), and its influence on inflammation and oxidative stress in the patients.Methods: 100 UC patients were randomely assigned to a control group given MSZ capsule treatment only, and a combination group treated with BTVCs and MSZ. Treatment effectiveness, inflammatory response, and oxidative stress in the two groups before and after treatment were compared.Results: The combination group had higher total effectiveness than the control group. The serum levels of MDA, high-sensitivity C-reactive protein (hs-CRP), TNF-α and interleukin-6 (IL-6) were lower, while serum levels of superoxide dismutase (SOD) and interleukin-10 (IL-10) were markedly increased in patients given combination treatment, when compared with controls. Pre-drug exposure UC disease activity index (UC-DAI) and clinical symptom scores were similar in both cohorts of patients, but the post-treatment scores were statistically decreased, especially in the combination group.Conclusion: The combined use of MSZ and BTVCs was more effective against UC than monotherapy, as it effectively relieved inflammation and oxidative stress in patients, resulting in better clinical efficacy.


Author(s):  
Lamda Souad ◽  
Naimi Dalila ◽  
Aggoun Cherifa

Objective: The present study was designed to evaluate the effect of hyperhomocysteinemia (Hhcy) induced by feeding rats high methionine diet on the colon wall. Colonic damages caused by Hhcy were compared with those induced by acetic –acid induced colitis.Methods: Sprague-Dawley rats (200-250g) were divided into four groups: group C (control), group M (received 1 g/kg methionine p. o. during 15 d), group A (colitis was induced by transrectal administration of acetic acid 4% on 8th day) and group MA (received methionine and acetic acid). At the end of the study, plasma homocysteine, C-reactive protein (CRP) and leukocytes (WBC) count were evaluated, all rats were sacrificed and distal 8 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and injuries were assessed macroscopically and histologically.Results: High methionine diet induced significant (P<0.001) increase of homocysteine (hcy), CRP levels and WBC count compared to control. Acetic acid rats showed a significant decrease of WBC count. Mixed treatment caused a significant increase of hcy, CRP and a significant decrease of WBC count. Our results showed that Hhcy causes significant damages and immune cells infiltration in all layers of the colonic wall.Conclusion: The present investigation demonstrated that Hhcy increased the major inflammatory markers as CRP and leukocytes count and produced transmural colitis in rats. Effect of Hhcy is more toxic on the colonic wall than acetic acid indeed while acetic acid lesions are localized in mucosa and submucosa the lesions of hcy extend to the all layers (mucosa, submucosa and muscularis propria). Acetic acid induced colitis in hyperhomocysteinemic rats increased the severity of colitis.


Author(s):  
Lamda Souad ◽  
Naimi Dalila ◽  
Aggoun Cherifa

Objective: The present study was designed to evaluate the effect of hyperhomocysteinemia (Hhcy) induced by feeding rats high methionine diet on the colon wall. Colonic damages caused by Hhcy were compared with those induced by acetic –acid induced colitis.Methods: Sprague-Dawley rats (200-250g) were divided into four groups: group C (control), group M (received 1 g/kg methionine p. o. during 15 d), group A (colitis was induced by transrectal administration of acetic acid 4% on 8th day) and group MA (received methionine and acetic acid). At the end of the study, plasma homocysteine, C-reactive protein (CRP) and leukocytes (WBC) count were evaluated, all rats were sacrificed and distal 8 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and injuries were assessed macroscopically and histologically.Results: High methionine diet induced significant (P<0.001) increase of homocysteine (hcy), CRP levels and WBC count compared to control. Acetic acid rats showed a significant decrease of WBC count. Mixed treatment caused a significant increase of hcy, CRP and a significant decrease of WBC count. Our results showed that Hhcy causes significant damages and immune cells infiltration in all layers of the colonic wall.Conclusion: The present investigation demonstrated that Hhcy increased the major inflammatory markers as CRP and leukocytes count and produced transmural colitis in rats. Effect of Hhcy is more toxic on the colonic wall than acetic acid indeed while acetic acid lesions are localized in mucosa and submucosa the lesions of hcy extend to the all layers (mucosa, submucosa and muscularis propria). Acetic acid induced colitis in hyperhomocysteinemic rats increased the severity of colitis.


2020 ◽  
Vol 52 (6) ◽  
pp. 675-682
Author(s):  
Guangmeng Xu ◽  
Yajuan Sun ◽  
Huaiqiang He ◽  
Qiuli Xue ◽  
Yajie Liu ◽  
...  

Abstract In this study, we aimed to explore the effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis. The mouse model of ulcerative colitis was established by medication, and 40 SPF C57BL/6J mice (8 weeks old) were randomly divided into normal group (healthy mice, n = 10), control group (sham-operated mice, n = 10), model group (model mice without any treatment, n = 10), and K252a group (model mice treated with 100 μmol/kg TrkB-PLC/IP3 pathway inhibitor for 5 days before clysis, n = 10). The results showed that mice in the model and K252a groups, as compared with normal and control groups, had no significant changes in the levels and protein expressions of serum tumor necrosis factor-α (TNF-α) and TNF-γ in the colon tissues (P&gt;0.05), and had a significant increase in disease activity index, colon mucosa damage index, tissue damage index scores, and levels and protein expressions of serum interleukin-4 (IL-4) and IL-8, but had a significant decrease in the level and protein expression of serum IL-10 (P&lt;0.05). Mice in the model and K252a groups showed blocked enterocyte cycle progression, elevated apoptosis ratio, and significantly increased mRNA and protein expressions of Caspase3, Bax, FasL, and Fas, but significantly reduced mRNA and protein expressions of p-TrkB, PLC-γ1, IP3, and Bcl-2 (P&lt;0.05). Moreover, intestinal inflammation and apoptosis induced by colitis in the K252a group became more aggravated by inhibiting the activity of TrkB-PLC/IP3 pathway. In conclusion, inhibition of TrkB-PLC/IP3 pathway can increase the expression of intestinal inflammatory factors and promote enterocyte apoptosis in mice with colitis.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jing-Wei Mao ◽  
Hai-Ying Tang ◽  
Ying-De Wang

Aim. To observe the disease activity index (DAI) and the colonic mucosa damage index (CMDI), detect the colonic mucosal expression of PPARγ, NF-κB, and TNF-αin rats with ulcerative colitis (UC), and to investigate the protective role of rosiglitazone in UC.Methods. Sprague-Dawley (SD) rats were divided into three groups: a control group, a rosiglitazone treatment group, and a UC model group. Rats were sacrificed on days 7, 14, 21, or 35 following administration of treatment after enema and DAI, CMDI and colonic expression of PPARγ, NF-κB, and TNF-αwere assessed.Results. In the UC model group, DAI, CDMI and the colonic expression of NF-κB and TNF-αincreased significantly compared to the control group at all timepoints, but PPARγdecreased significantly. Furthermore, in the rosiglitazone treatment group, DAI and CMDI decreased significantly on the 14-day, 21-day, and 35-day timepoints compared to the UC model group; the colonic expression of NF-κB and TNF-αdecreased compared to UC model group at all timepoints, but the PPARγexpression increased significantly.Conclusions. Rosiglitazone can alleviate colonic mucosal inflammation and have the protective role on UC by upregulating PPARγexpression and downregulating NF-κB and TNF-αexpression.


Author(s):  
J. Santoantonio ◽  
L. Yazigi ◽  
E. I. Sato

The purpose of this study was to investigate the personality characteristics in adolescents with SLE. The research design is a case-control study by means of the Rorschach Method and the Wechsler Intelligence Scale. Study group: 30 female adolescents with lupus, 12–17 years of age. The SLE Disease Activity Index was administered during the period of psychological evaluation. Control group: 32 nonpatient adolescents were matched for age, sex, and socioeconomic level. In the Wechsler Intelligence Scale the mean IQ of the experimental group was significantly lower than that of the control group (77 and 98, respectively, p < .001). In the Rorschach, the lupus patients showed greater difficulty in interpersonal interactions, although they displayed the resources to process affect and to cope with stressful situations. A positive moderate correlation (p = .069) between the activity index of the disease and the affect constriction proportion of the Rorschach was observed: the higher the SLEDAI score, the lower the capacity to process affect. There is a negative correlation between the activity index of the disease and the IQ (p = .001): with a higher activity index of the disease, less intellectual resources are available.


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