Perindopril and/or α‑pinene mitigate acetic acid-induced ulcerative colitis via regulation of JAK/STAT3/SOCS3 axis and miR-98-5p expression in rats

Ulcerative colitis (UC) is one of the most well-known types of inflammatory bowel disease that manifests as recurrent inflammation of rectum and colon. The goal of this study is to evaluate the protective effects of shark liver oil (SLO) on acetic acid-induced ulcerative colitis in rats. Eighty induced UC rats were randomly divided into ten equal groups and received the following treatments for seven days: 1 ml of normal saline rectally, 1 ml of gel base (carboxymethyl cellulose) rectally, 10 mg/kg of Asacol rectally, 10 mg/kg of mesalazine orally, 5% gel form of SLO rectally, 10% gel form of SLO rectally, 200 mg of SLO orally, and 400 mg of SLO orally. We examined the oxidative stress indices, histopathological features, and body weight changes, as well as the function of the liver and kidneys at the end of treatment. Administration of 10% rectal and 400 mg oral SLO resulted in a significant weight gain. Also, glutathione peroxidase activity was significantly higher in 5% and 10% SLO-treated groups, and elevated superoxide dismutase activity in rats that received 5% SLO was observed compared to negative control and Asacol groups. While no significant changes were observed in most of the kidney and liver function markers, higher levels of aspartate aminotransferase were detected in the group that received 400 mg SLO orally compared to negative control and Asacol groups. Many histopathological signs of improvement were observed in mesalazine, Asacol, and SLO groups. There were no significant changes detected in the mean rank among different groups. Our data indicate that SLO supplementation could improve the amelioration of acetic acid-induced UC in rats due to its antioxidant effects.

Background: Ulcerative colitis (UC) is an inflammatory bowel disorder affecting the colonic mucosa, characterized by intense inflammation and mucosal damage. The present study aimed to evaluate the protective effect of the Trigonellafoenum-graecum L. (TFG) seeds in acetic acid-induced UC in rats. Materials and Methods: Male rats (n=30) were distributed into 5 groups as normal control, UC, standard, and two test groups. Colitis was induced by acetic acid in all the groups except the normal control group. Normal control and UC group received distilled water, the standard group was administered sulfasalazine at 100mg/kg body weight (bw), and test groups, TFG-I, and TFG-II received TFG seed extract at 500 and 1000 mg/kg bw, respectively. The duration of treatment was 7 days, and colitis was induced on day 8. Animals were sacrificed on day 9 and colonic tissue was dissected and collected for biochemical, molecular, and histological analysis. Results: The disease activity index score in standard, TFG-I, and TFG-II (3.33±0.21, 2.66±0.21, and 3.50±0.22) was significantly lesser (P<0.05) than scores in the UC group (4±0.01). The macroscopic score indicating the intensity of mucosal inflammation was significantly decreased (P≤ 0.01) to4.0±0.25, 3.16±0.30, and 3.83±0.40 in standard, TFG-I, and TFG-II groups, respectively compared to the UC group (4.66±0.21). Similarly, there was a significant reduction (P≤0.05) in histological scores of the standard, TFG-I, TFG-II (3.5±0.34, 1.25±0.34, 3.25±0.34) groups compared to the UC group (4.75±0.34). Biochemical assessment in the standard and test groups showed significant increase (P<0.05) in total protein, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) levels whereas significant reduction (P<0.01) in malondialdehyde (MDA) levels compared to UC group. The pro-inflammatory cytokine TNF-α levels were significantly decreased (P<0.01) in standard, TFG-I, and TFG-II (-1.75±0.007, -0.27±0.17 and -0.51±0.002) when compared to the UC group (0.20±0.02). Conclusion: The study demonstrates the ability of TFG seeds in reducing the inflammatory and oxidative stress induced mucosal damage in acetic acid-induced UC in rats.

Background Ulcerative colitis is a chronic mucosal inflammation of the large intestine mainly affecting the colon and rectum. The lack of effective and safe therapeutic agents led to the identification of new therapeutic agents to effectively manage the symptoms and complications of ulcerative colitis. The present study aimed to evaluate the protective effect of sodium benzoate in acetic acid-induced ulcerative colitis in rats. Methods Infusion of 3% acetic acid in the colon through the rectum was done to construct a rat model of ulcerative colitis. After 5 days of infusion, macroscopic, biochemical, and histopathological examinations and disease activity scoring of the colon were done to assess colonic damage. Results Acetic acid infusion resulted in severe inflammation in the colon assessed macroscopically and histopathologically. Moreover, it also led to increase in myeloperoxidase (MPO) and reduction in glutathione (GSH) levels. In the present study, repeated administration of sodium benzoate (400 and 800 mg/kg i.p.) and sulfasalazine (500 mg/kg orally) for 7 days, i.e. 2 days before and continued for 5 days after acetic acid infusion, significantly attenuated macroscopic damage and disease activity score as compared to disease control. Further, it also significantly reduced the levels of MPO and enhanced colonic levels of reduced GSH. However, the lower dose of sodium benzoate (200 mg/kg) did not show sufficient protective effect in acetic acid-induced ulcerative colitis. Further, sodium benzoate per se did not show any effect in normal rats. Conclusions The observed protective effect of sodium benzoate may be due to its antioxidant and anti-inflammatory activities in an ulcerative colitis model.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that result in recurrent inflammation plus ulcers of the colon and rectum. Recently, mesenchymal stem cell-derived exosomes MSC-EXs have shown a lot of promise for the treatment of gut disorders, with cell regeneration and angiogenesis. Green tea polyphenols (GTPs) display specific beneficial effects on health and pathologies. The aim of this study was to explore the possible effect of MSC-EXs and GTPs on acetic acid-induced UC in rats. Sixty adult male rats were divided into five groups: group I, control group; group II, UC; group ΙIΙ, UC treated with GTPs; group ΙV, UC treated with MSC-EXs; and group V, UC treated with combined GTPs and MSC-EXs. Colonic samples were processed for histological and immunohistochemical methods. Expression of CXCR2 and TLR4 levels was measured. Groups ΙI and III showed ulceration, loss of surface columnar epithelium, disturbed crypt architecture with few goblet cells, and many cellular infiltrations with the overexpression of CXCR2 and TLR4. Group IV showed attenuation of some histological changes. Group V showed improvement of the most histological and immunohistochemical changes described previously. MSC-EXs represent future therapeutic hopes for chronic intestinal inflammatory states, keeping the integrity of innate immunity through their regenerative and anti-inflammatory effects. The combination of GTPs and MSC-EXs was more effective and produced an additive effect than using MSC-EXs alone.

Ulcerative colitis (UC) is a chronic intestinal inflammation. Common clinical symptoms are weight loss, diarrhea, ulcers, and inflammation. Aloe vera (AV) has several medicinal properties including antioxidant, anti-inflammatory analgesic, and improvement of gastric and skin ulcers. This study aimed to investigate the protective and therapeutic effects of AV gel on acetic acid-induced UC in rats. UC was induced in 48 rats by injection of 4% acetic acid into the rectum. Protective and treatment groups received treatments 7 days before and after the induction of colitis, respectively. The negative control group, the positive control group, and AV groups received distilled water, sulfasalazine, and 50 and 300 mg/kg of gel extract, respectively. Water and food intake and body weight changes were recorded. The extent of the mucosal ulcers, colon tissue thickening, and mucosal bleeding were scored by the Gerald classification system score (microscopy observations). Slides of tissues were prepared for pathologic assay using the modified Wallace method (macroscopic observations). The results of the macroscopic and microscopic examination showed protective and therapeutic effects of 50 mg/kg dose of AV on acetic acid-induced colitis in rats which reduces the inflammation, ulcers and tissue damage compared with negative control (p < 0.05). There were no significant changes in the amount of water and food intake, body weight changes, and colon weight in protective and treatment groups. Based on the results, AV gel could be used to improve the symptoms of UC, as well as prevent people who are susceptible to the UC.

Ulcerative Colitis (UC) is an inflammatory bowel disorder that affects colon and rectum. Treatments in many UC patients remain variably effective and are associated with considerable adverse effects. So the present study was undertaken to explore the antiinflammatory effects of emu oil, glycyrrhizin, and combination of emu oil and glycyrrhizin in acetic acid-induced UC in rats. UC was induced by intracolonic instillation of 5% acetic acid in rats. Emu oil and glycyrrhizin were orally administered to test groups. Severity of colitis was scored macroscopically and microscopically. The levels of myeloperoxidase and antioxidant enzymes namely catalase, superoxide dismutase and glutathione peroxidase were assessed spectrophotometrically. Expressions of PPARγ and TNFα were studied by real-time PCR. Acetic acid caused severe damage to colon and rectum. Emu oil and glycyrrhizin were found to significantly reduce macroscopic and microscopic lesions and decrease levels of myeloperoxidase. There was a significant improvement of antioxidant levels in treatment groups compared to acetic acid group. Combination of emu oil and glycyrrhizin showed a markedly greater modulation of PPARγ and TNFα expression than emu oil and glycyrrhizin when administered alone. Combination of emu oil and glycyrrhizin might have had synergistic effects in regulating PPARγ and TNFα. Further studies on mechanism of action of emu oil and glycyrrhizin combination would pave the way to define possibility of this combination as effective in the management of UC.

Introduction:Natural plants always provide core compounds for new drug development. In the present life and food style, inflammatory bowel disease has become common and needs a lead compound for its drug development.Aim:To evaluate the effect of Agave americana Linn. leaf extract in acetic acid-induced ulcerative colitis in rats based on its traditional anti-inflammatory use.Materials and Methods:Male Wistar rats were pretreated with A. americana leaf extract in the dose of 200 and 400 mg/kg p.o. daily for 7 days. On 8th day, 2 ml of 4% v/v acetic acid in saline was instilled into rats’ rectum. Prednisolone was used as standard drug and it was administered on the day of acetic acid instillation and continued for 3 days. Extract treatment was continued till 11th day. Body weight, ulcer score, colonic muscle contraction, antioxidant activity and histopathology were studied. Statistical analysis was performed using Parametric one-way analysis of variance followed by Tukey's posttest.Results:A. americana have retained total body weight significantly (P < 0.01) and decreased colon weight/length ratio. Extract have shown a significant decrease (P < 0.001) in ulcer scores, myeloperoxidase, lipid peroxidase activity. Further, extract have shown significant improvement in colonic muscle contraction, histopathology of colon etc., which is comparable with standard drug.Conclusion:A. americana possess protective effect against acetic acid-induced colitis in rats.

Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats.

Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment. To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations. In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67±0.18 and 1.73±0.21 (p<0.05), respectively, compared to the UC control group (3.21±0.31), and were higher than that of the group given the standard treatment of 100 mg/kg SSZ (1.10±0.09). The treatment groups with 50 and 100 mg/kg of SCG showed a lower clinical gross lesion score than the UC control group (2.91±0.28 and 2.10±0.43, vs. 4.49±0.61, p<0.05) and were higher than the standard group (0.95±0.18). Treatment with SCG (100 mg/kg) decreased the macroscopic scores significantly compared to the UC control group (p<0.05) on the 8th day. SCG (100mg/kg) decreased significantly the clinical activity score, gross lesion, and percentage-affected area compared to the UC controls on the 8th day.

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.

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.

Ulcerative colitis (UC) is an inflammatory bowel disease involving chronic andrecurring colon inflammation. Current management protocols are limited byadverse effects or short-term symptomatic relief. We aimed to investigate thepossible therapeutic prospect of low dose gamma (γ) irradiation or apigenintreatment in acetic acid-induced UC in rats. Induction of UC was carried out byinstallation of acetic acid intra-rectally. One hour post-induction, ratsreceived a sole dose of γ-radiation (0.5 Gray) or were treated with apigenin(3 mg/kg/day, peroral) for 7 successive days. Antioxidant and anti-inflammatoryeffects of both agents were assessed via determination of colon malondialdehyde(MDA), reduced glutathione (GSH), total nitrate/nitrite (NOx), mucosal addressincell adhesion molecule-1 (MAdCAM-1), and interleukin-1beta (IL-1β) contents aswell as myeloperoxidase (MPO) activity. Body weight (BW), colon weight/length(W/L) ratio, disease activity index (DAI), and histopathological changes wereevaluated. Gamma irradiation and apigenin significantly ameliorated the aceticacid-induced biochemical and histopathological changes. Both therapeuticapproaches significantly restored colon contents of the investigated biomarkers.They modulated BW, colon W/L ratio and DAI. This study proposes low doseγ-irradiation as a new therapeutic candidate for the management of UC. We alsoconcluded that apigenin exhibited therapeutic benefits in UC management.

Background: Antioxidant therapy has gained attention for the treatment of ulcerative colitis (UC). The excessive generation of reactive oxygen/nitrogen species in the gastrointestinal tract increases oxidative stress, thereby leading to antioxidant defense depletion, lipid peroxidation, inflammation, tissue damage, and ulceration. Spirulina platensis (SP) and honey are excellent sources of potent antioxidants such as polyphenols and other bioactive compounds. We aimed to investigate antioxidant and anti-inflammatory effects of honey and SP in comparison with sulfasalazine (SSZ) and mesalazine on acetic acid-induced colitis (AA-colitis) in rats. Materials and Methods: Fifty-six Sprague Dawley male rats were allocated to seven groups, with each group comprising eight rats. UC was induced, except in normal controls (NC). All groups received oral treatments for seven days. The normal saline solution of 2 mL was intrarectally administered to the NC group. The AA-colitis and NC groups received 2 mL acetic acid intrarectally as a single dose and 2 mL normal saline for seven consecutive days orally. The mesalazine group received 100 mg/kg mesalazine, the SSZ group 360 mg/kg SSZ, the honey or H group 1 mL honey diluted with 1 mL distilled water, the SH group 1g/kg SP and 1 mL honey, and the SP group 1g/kg SP. After clinical activity score assessment, the rats were sacrificed. Colonic weight/length ratio, prostaglandin E2 (PGE2), myeloperoxidase (MPO), nitric oxide (NO), malondialdehyde (MDA), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), glutathione peroxidase (GPx), total antioxidant capacity (TAC), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured. Colonic histopathological changes were observed microscopically. Results: Treatment of UC with SP, honey, and combination regimen significantly reduced TNF-α, IL-1β, IL-6, MDA, MPO, NO, and PGE2, and increased TAC, GSH, GPx, and SOD in interventional groups compared to the AA-colitis group (P<0.05). Conclusion: Honey and SP might be beneficial food supplements for medical nutrition therapy in UC.

Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress

The development of effective treatment strategies has been hindered by the complex pathogenesis of ulcerative colitis (UC). UC patients treated with current therapeutic approaches experienced either treatment failure or suffered excessive adverse reactions. Overactivity of NLRP3 inflammasome enhances inflammation, resulting in aggravation of colonic damage. We were interested in exploring, for the first time, the potential coloprotective effect of dapagliflozin (DPZ) on acetic acid-induced UC in rats in comparison with 5-ASA. DPZ improved histologic and macroscopic features of colon tissues and prolonged survival of UC rats. DPZ also prevented colon shortening and declined disease activity. Additionally, DPZ lessened colon tissue neutrophil content and improved antioxidant defense machinery. Further, DPZ specifically declined the colonic inflammatory marker IL-6 and upregulated the anti-inflammatory cytokine IL-10. The pyroptosis process is constrained in consequence of the repressed caspase-1 activity and caspase-1-dependent release of the bioactive cytokines IL-1β and IL-18. These protective effects might be attributed to that DPZ on the one hand, prevented the priming step (signal 1) of NLRP3 inflammasome activation as revealed by modulating NFκB/AMPK interplay and on the other hand, inhibited the activation step (signal 2) as indicated by interrupting NLRP3/caspase-1 signaling. Since DPZ was found to be safe and well tolerated by healthy volunteers with no evidence of hypoglycemia, it might show promise in the future management of UC. However, further investigations are warranted to confirm the reversal of injury and that the coloprotective effect is substantial.