Colitis Control Group Research Articles

Therapeutic potential of Capparis spinosa in experimental model of acute acetic acid-induced colitis: Anti-inflammatory and antioxidant effects

IntroductionThis study examined the anti-inflammatory and antioxidant properties of Capparis spinosa L. (caper) in order to determine its medicinal potential in the treatment of acute colitis. MethodSixty male rats were divided into six groups. After the experimental period, distal colonic extension was collected for determination of colonic damage, oxidative stress markers, along with antioxidant markers. The impact of altered levels of inflammatory cytokines in colon tissues on the underlying mechanisms examined. ResultsThe results showed that administering different doses of caper led to significant decreases in TNF-α and IL-6 levels when compared to the control colitis group (p < 0.001). Caper treatment effectively lowered elevated oxidative stress factors (MDA, NO, and MPO) compared to the control colitis group (p < 0.001). Caper treatment resulted in a significant increase in antioxidant factors (CAT, SOD, and GSH) compared with the control colitis group (p < 0.001).Significant improvements in tissue repair were observed in caper-treated groups compared to positives and control colitis (p < 0.001). ConclusionThe study highlights caper may be useful in the treatment of acute colitis due to its ameliorative effects on inflammation, oxidative stress, and tissue repair.

Protective Role of Limosilactobacillus fermentum Lf2 and Its Exopolysaccharides (EPS) in a TNBS-Induced Chronic Colitis Mouse Model

Limosilactobacillus fermentum Lf2 (Lf2) is an autochthonous strain that produces high levels of exopolysaccharides (EPS). The objective of this work was to evaluate the probiotic potential of Lf2 and its relationship with these metabolites in a mouse model of TNBS (trinitrobenzene sulfonic acid)-induced chronic colitis. Mice were treated intrarectally with increasing doses of TNBS resuspended in 50% ethanol for 14 days. In parallel, they received different treatments by gavage (lactose 10% as the matrix): freeze-dried Lf2 (L); purified EPS (E); and lactose 10% (T). A healthy control group (H) was treated with 50% alcohol without TNBS (intrarectally) and 10% lactose (by gavage). In the small intestine, there was a significant increase in IgA levels for the group that received EPS and a decrease in IFN-γ for mice treated with the strain compared to the other groups. In the large intestine, IL-2 and IFN-γ presented the lowest levels in the groups treated with EPS and the strain. The concentrations of acetic and propionic acids in mice that received Lf2 were the highest, while the levels of butyric acid were comparable to the healthy control group. An increase in the abundance of SCFA-producing bacteria was observed for mice treated with EPS and the strain in comparison with the colitis control group. The enzyme activity of catalase was higher in all the treatments compared to the TNBS-induced colitis control mice. To summarize the results obtained, a principal component analysis (PCA) was performed, clearly grouping the treatments in different clusters according to the variables studied. This is one of the first studies to address the role of a potential probiotic strain in a chronic colitis mouse model, trying to elucidate the relationship between its properties and the EPS synthesized.

Anti-ulcerative colitis effects of chemically characterized extracts from Calliandra haematocephala in acetic acid-induced ulcerative colitis.

Background: Ulcerative colitis is a chronic immune-mediated inflammatory bowel disease that involves inflammation and ulcers of the colon and rectum. To date, no definite cure for this disease is available. Objective: The objective of the current study was to assess the effect of Calliandra haematocephala on inflammatory mediators and oxidative stress markers for the exploration of its anti-ulcerative colitis activity in rat models of acetic acid-induced ulcerative colitis. Methods: Methanolic and n-hexane extracts of areal parts of the plant were prepared by cold extraction method. Phytochemical analysis of both extracts was performed by qualitative analysis, quantitative methods, and high-performance liquid chromatography (HPLC). Prednisone at 2mg/kg dose and plant extracts at 250, 500, and 750mg/kg doses were given to Wistar rats for 11days, which were given acetic acid on 8th day through the trans-rectal route for the induction of ulcerative colitis. A comparison of treatment groups was done with a normal control group and a colitis control group. To evaluate the anti-ulcerative colitis activity of Calliandra haematocephala, different parameters such as colon macroscopic damage, ulcer index, oxidative stress markers, histopathological examination, and mRNA expression of pro and anti-inflammatory mediators were evaluated. mRNA expression analysis was carried out by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Results: The phytochemical evaluation revealed polyphenols, flavonoids, tannins, alkaloids, and sterols in both extracts of the plant. Results of the present study exhibited that both extracts attenuated the large bowel inflammation and prevented colon ulceration at all tested doses. Macroscopic damage and ulcer scoreswere significantly decreased by both extracts. Malondialdehyde (MDA) levels and nitrite/nitrate concentrations in colon tissues were returned to normal levels while superoxide dismutase (SOD) activity was significantly improved by all doses. Histopathological examination exhibited that both extracts prevented the inflammatory changes, cellular infiltration, and colon thickening. Gene expression analysis by RT-qPCR revealed the downregulation of pro-inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) whereas the anti-inflammatory cytokines including Interleukin-4 (IL-4) and Interleukin-10 (IL-10) were found to be upregulated in treated rats. Conclusion: It was concluded based on study outcomes that methanolic and n-hexane extracts of Calliandra haematocephala exhibited anti-ulcerative colitis activity through modulation of antioxidant defense mechanisms and the immune system. In this context, C. haematocephala can be considered as a potential therapeutic approach for cure of ulcerative colitis after bioassay-directed isolation of bioactive phytochemicals and clinical evaluation.

Evaluation of the Anti-Oxidative Effects of Monocyte Cells Treated with Bone Marrow Mesenchymal Stem Cells Supernatant on Experimental Colitis in BALB/c Mice

Background: Alternate activation of monocytes could induce anti-inflammatory impacts. This study aimed to investigate whether monocyte cells treated with bone marrow mesenchymal stem cells supernatant (MSC-Sp) could improve anti-inflammatory responses as a cell transfer therapy for colitis. Materials and Methods: The induction of experimental colitis was done by acetic acid in four groups of male BALB/c mice, including the control colitis, treated-monocytes, non-treated-monocytes, and mesalazine groups. Following MSCs culture, the supernatant was harvested, and then 50% conditioned media, or negative control media was added to the monocytes for 24 h. After ten days, peritoneal injection of treated or non-treated-monocytes (105 cells/100µL) was performed in animals' relevant groups of colitis. Ten days later, the oxidative stress profile and histopathological evaluation of colon tissue were assessed. Results: Treated monocytes showed a significant improvement in the oxidative stress profile, namely myeloperoxidase (0.126±0.008), nitric oxide (0.153±0.01), and malondialdehyde (0.148±0.014) compared to the control colitis group (P&lt;0.05). Also, histopathological results revealed that the rate of damage in the treated-monocytes group was less than in normal mice. Conclusion: Our study indicated that the treated monocytes had anti-oxidative potential in colitis mice and were usable as a complementary therapy. [GMJ.2021;10:e2131]

Impact of Eugenol on Acetic Acid-induced Colitis in Rats

Background: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease, are immune-mediated chronic relapsing intestinal disorders characterized by the presence of an acute or chronic inflammatory process in the bowel wall. Eugenol essential oil is used in traditional medicine to treat digestive disorders such as gastrointestinal ulcers, indigestion, and inflammation of the intestines. Aim: To investigate the effects of Eugenol on colitis in rat models. Methods: Eugenol was administered per rectum (5 and 10 mg/kg) and intraperitoneally (0.25 and 0.5 mg/kg) for 6 days after induction of colitis by acetic acid. The changes were examined macroscopically, histologically, and biochemically and compared with Dexamethasone. Results: Results showed a significant decrease in the macroscopic damage score (P &lt; 0.05), and reduction in the weight ratio of the colon (P &lt; 0.01), the histological signs of inflammation (P &lt; 0.01) such as infiltration of lymphocytes and macrophages into the mucosa, mucin depletion, crypt abscess, edema, and tissue damage, as well as leukocyte accumulation and myeloperoxidase level in compare with the colitis control group. Conclusion: This animal trial demonstrates the beneficial anti-inflammatory and wound-healing effects of Eugenol in the treatment of acetic acid-induced colitis in rats. Eugenol can potentially be advantageous as a supplemental remedy for the treatment of IBD.

Dual role of melatonin as an anti-colitis and anti-extra intestinal alterations against acetic acid-induced colitis model in rats

The available ulcerative colitis drugs exhibit limited outcomes and adverse side effects. Therefore, our study aimed to investigate the therapeutic efficacy of melatonin in acetic acid (AA)-induced colitis to establish a possible treatment for colitis and its impacts on vital organs. Following colitis induction (2 ml 5% AA, rectally), rats were orally received melatonin (5 mg/kg) once per day for 6 days after colitis induction. Then, histopathological examination of colon, kidney, liver, and spleen was conducted, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and total antioxidant capacity (TAC) levels were assessed in colon tissue. Colitis induction in untreated rats caused necrotic effects in colon tissues, a significant increase in colonic IL-1β, TNF-α, MPO, and MDA levels, and a remarkable decrease in GSH and TAC levels in colon tissue in comparison to the control group. Meanwhile, melatonin treatment reversed these parameters by improving the microscopic and macroscopic colitis features and extra-intestinal (kidney, liver, and spleen) changes in all treated rats compared to the colitis control group. These results denote a reduction in colitis severity due to the anti-inflammatory and anti-oxidative effects of melatonin and its positive impact on the vital organs.

Evaluation of Anticolitis and Antioxidant Properties of Bixa orellana (Bixaceae) Leaf Hydroethanolic Extract on Acetic Acid-Induced Ulcerative Colitis in Rats

BackgroundUlcerative colitis is an idiopathic inflammatory bowel disease characterized by tissue damage, diarrhea, anemia, and loss of body weight. Tissue damage occurs as a result of uncontrolled activation of the immune response and an increase in free radicals, which have a strong effect on the pathogenesis of inflammatory bowel disease. The incidence and prevalence of this inflammatory disease continue to increase worldwide. Maceration of Bixa orellana leaves in palm wine is used in traditional medicine to treat diarrhea, dysentery, and hemorrhoids in the Adamaoua region of Cameroon.ObjectiveThe present work evaluated the preclinical effects (ie, antioxidant, hematological, and histological activities) of the hydroethanolic extract of Bixa orellana leaves in an in vivo, rat acetic acid-induced ulcerative colitis model.MethodsThirty-six female rats weighing between 165 and 180 g were fasted for 18 hours and then anesthetized with ether. A dose of 1 mL acetic acid (5%) was administered rectally through a catheter in all rats except the normal control group, which received distilled water (1 mL) instead. Treatments began 48 hours after rectal administrations of acetic acid or water, and all animals were treated twice daily for 7 days. The normal control group and the colitis control group received PO distilled water (10 mL/kg), the positive control received orally loperamide (5 mg/kg, and the 3 test groups received orally the hydroethanolic extract of Bixa orellana at 100, 200, and 400 mg/kg, respectively. During treatment, the number of diarrheal stools and weight change were assessed. At the end of the treatment, the animals were put to death under ether anesthesia. Blood was collected postmortem for evaluation of hematological and antioxidant parameters. The abdomen was opened via a midline incision and the colon was removed and emptied of all contents to assess histological and antioxidant parameters.ResultsDuring treatment, the number of diarrheal stools was significantly decreased from day 3 in animals treated with 100 (P < 0.05), 200 (P < 0.05), and 400 (P < 0.01) mg/kg extract compared with the colitis control group. The change in body weight of all extract-treated rats decreased significantly from day 3 (–5.55%; P < 0.05) to day 8 (–13.80%; P < 0.01) compared with the normal control. In the colitis control, this change ranges from –6.15% on day 2 to –15.13% on day 8. Extract treatment with 100, 200, and 400 mg/kg significantly reduced (P < 0.05) the number of lesions and the relative weight of the colon. The levels of red blood cells, neutrophils, and total white blood cells decreased in the colitis control group, whereas treatment with the extract at doses of 100, 200, and 400 mg/kg was associated with a significant increase in these hematological parameters. Catalase and superoxide dismutase activity and glutathione concentrations all increased significantly (P < 0.01) in blood and colon in all extract-treated animals, whereas levels of malondialdehyde and nitric oxide were significantly decreased (P < 0.01) compared with the colitis control animals.ConclusionsThe hydroethanolic extract of Bixa orellana leaves had protective effects against acetic acid-induced ulcerative colitis in rats that was associated with inhibited production of free radicals believed to be responsible for oxidative stress, hematological disorders, and tissue damage in this animal model.

Evaluation of the Anti-Oxidative Effects of Monocyte Cells Treated with Bone Marrow Mesenchymal Stem Cells Supernatant on Experimental Colitis in BALB/c Mice

Background: Alternate activation of monocytes could induce anti-inflammatory impacts. This study aimed to investigate whether monocyte cells treated with bone marrow mesenchymal stem cells supernatant (MSC-Sp) could improve anti-inflammatory responses as a cell transfer therapy for colitis. Materials and Methods: The induction of experimental colitis was done by acetic acid in four groups of male BALB/c mice, including the control colitis, treated-monocytes, non-treated-monocytes, and mesalazine groups. Following MSCs culture, the supernatant was harvested, and then 50% conditioned media, or negative control media was added to the monocytes for 24 h. After ten days, peritoneal injection of treated or non-treated-monocytes (105 cells/100µL) was performed in animals' relevant groups of colitis. Ten days later, the oxidative stress profile and histopathological evaluation of colon tissue were assessed. Results: Treated monocytes showed a significant improvement in the oxidative stress profile, namely myeloperoxidase (0.126±0.008), nitric oxide (0.153±0.01), and malondialdehyde (0.148±0.014) compared to the control colitis group (P&lt;0.05). Also, histopathological results revealed that the rate of damage in the treated-monocytes group was less than in normal mice. Conclusion: Our study indicated that the treated monocytes had anti-oxidative potential in colitis mice and were usable as a complementary therapy. [GMJ.2021;10:e2131]

Anti-inflammatory effect of pregabalin on acetic acid-induced colitis in the rats.

Background and purpose:Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease characterized by the inflammation of the intestine. The available medicinal treatments for IBD are not efficacious enough since they exert various adverse effects. Therefore, the search for new therapeutic agents should be continued. The present study aimed to assess the anti-inflammatory effects of pregabalin on acetic acid-induced colitis in rats.Experimental approach:Using 2 mL of 3% acetic acid solution, colitis was intra-rectally induced in rats. Animals were randomly divided into 6 groups including the normal group, colitis control group, pregabalin treatment groups (30, 50, and 100 mg/kg; i.p., respectively), and dexamethasone treatment group (1 mg/kg; i.p.). Macroscopic, microscopic, and biochemical (myeloperoxidase, tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta) examinations were used to evaluate the efficacy of pregabalin in the inflamed colon.Findings/Results:All the applied doses of pregabalin significantly decreased the severity of macroscopic and microscopic colonic damages including ulcer severity, ulcer area, percentage of necrosis, and total colitis index compared to the colitis control group. These results were confirmed by the reduced colonic concentration of tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, and myeloperoxidase activity.Conclusion and implications:Results of this study indicated that pregabalin administration has beneficial effects upon the treatment of experimental colitis, which might be partly due to its anti-inflammatory properties.

The Effect of Probiotic and Omega-3 Supplements on Total Oxidant and Total Antioxidant Levels in Experimental Colitis

Objective: Treatment of inflammatory bowel disease (IBD) usually involves medical therapy. For this reason, it is recommended to seek alternative treatment methods such as nutritional therapy. The aim of the study is to evaluate the effects of probiotics and omega-3 fatty acids on total oxidant and total antioxidant levels in an experimental colitis model.Methods: Mice were randomly divided into five groups (n= 10/group) as healthy group, colitis group, group treated with probiotics (VSL#3), group treated with omega-3 (w-3), and group treated with both probiotics and omega-3. To induce experimental colitis, 200 mg/kg dinitrobenzene sulfonic acid (DNBS) + 30% ethanol combination was rectally administered to anesthetized mice. Total oxidant (TOS) and total antioxidant (TAS) levels were measured at the tissue level.Results: Lower concentrations of TOS were observed in the probiotics groups (2.11±0.23 mmol H2O2 Eq/L), probiotics+omega-3 (2.56±1.18 mmol H2O2 Eq/L), and omega-3 (3.02±1.88 mmol H2O2 Eq/L) groups compared to the colitis group (3.11±0.91 mmol H2O2 Eq/L) (p&amp;gt;0.05). Higher TOS and TAS level were observed in the control colitis group compared to other groups; however, the differences were not statistically significant.Conclusion: Our findings showed that TAS and TOS levels were positively affected by the use of probiotic supplements in IBD. It was determined that using w-3 alone was ineffective in decreasing TOS levels. Studies with higher dosages and longer treatment.

An investigation of the anti-inflammatory effects of gabapentin on acetic acid-induced colitis in rats.

Inflammatory bowel disease (IBD) is considered a chronic inflammatory gastrointestinal disease with treatment options which exhibit low efficacies and lead to considerable side effects. Hence, the challenge to alleviate IBD complications is remained to be resolved. The purpose of this study is evaluating anti-inflammatory impacts of gabapentin on acetic acid-induced colitis in rats. Colitis was induced by the instillation of 2mL of 3% acetic acid solution into rat's colons. Rats were randomly allocated into six groups including normal group, colitis control group, gabapentin-treated groups (25, 50, and 100mg/kg; i.p.), and dexamethasone-treated group (1mg/kg; i.p.). Based on the macroscopic assessment besides histological and biochemical findings [myeloperoxidase (MPO), pro-inflammatory cytokines], the efficacy of gabapentin was investigated. Gabapentin (50 and 100mg/kg), and dexamethasone considerably reduced macroscopic and microscopic colonic lesions induced by acetic acid in rats in comparison with colitis control group. These results were confirmed by reduced levels of MPO activity and colonic concentrations of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha, in inflamed colon tissue. Our data demonstrated that gabapentin exerts profitable impacts in experimental colitis that might be ascribed to its anti-inflammatory features and thus can be a potential therapeutic agent for IBD treatment.

Non-Adherent Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Clinical Manifestations and Inflammation in an Experimental Model of Ulcerative Colitis in Rats.

Background: Functional and developmental versatility of mesenchymal stem cells (MSCs) have generated great interest in their clinical application. Recently, it has been proposed that the non-adherent population of bone marrow cells can differentiate to MSCs in vitro. The present study aimed to compare the anti-inflammatory potentials of adherent and non-adherent MSCs in an experimental model of ulcerative colitis (UC) in rats.Methods: The present experimental study was conducted at the School of Veterinary Medicine, Urmia University (Urmia, Iran) during March-May 2018. UC was induced using acetic acid in three groups of male Wistar rats, namely the control colitis, adherent MSCs treated, and non-adherent MSCs treated groups. Adherent and non-adherent MSCs were collected, characterized, and proliferated. The isolated cells were injected into the peritoneum of the respective groups of colitis rats. After 10 days, the animals were evaluated for gross and microscopic pathology, production of inflammatory mediators, and stress oxidative profile in the gut tissue. The statistical analysis was performed using SPSS software (version 23.0). P<0.05 was considered statistically significant.Results: The non-adherent MSCs had almost similar therapeutic potency compared to the adherent MSCs (P=0.12). They significantly reduced the level of inflammatory mediators and improved the oxidative stress profile in colonic tissue compared to the control colitis group (P=0.0001).Conclusion: The molecular assays and histopathological assessment revealed that the non-adherent MSCs not only had anti-inflammatory and regulatory potency but also enhanced tissue regeneration in UC rats. Therefore, the non-adherent fraction of bone marrow-derived MSCs could be used as a complementary source of MSCs in stem cell therapies.

Amelioration of murine experimental colitis using biocompatible cyclosporine A lipid carriers.

Lipoproteins are biodegradable and biocompatible natural carriers that can be utilized for the transport of hydrophobic drugs, such as cyclosporin A (CycloA), a calcineurin inhibitor utilized for the inflammatory bowel disease, such as ulcerative colitis. A major limitation in the drug treatment of inflammatory bowel disease is the inability to deliver the drug selectively toward the inflamed tissues. Nanotechnology-based drug delivery systems have led to an amelioration of the therapeutic selectivity, but still the majority of the entrapped drug is eliminated without exercising a therapeutic effect. The present study aimed to prepare three lipoprotein formulations (HDL-, LDL-, and VLDL-based) loaded with cyclosporin A for the treatment of colitis in a murine model. After an intravenous injection of a drug dose of 2mg/kg, clinical activity (colon weight/length ratio) and therapeutic effects (evaluated by the inflammatory markers MPO and TNF-α) were compared with those of the untreated colitis control group. All CycloA-containing lipoproteins reduced clinical activity, with a significant decrease in the case of LDL-CycloA formulation, which also led to the higher therapeutic effect.

The Healing Effects of Hydroalcoholic Extract of Carum copticum L. on Experimental Colitis in Rats.

Background:Ulcerative colitis is an inflammatory disease with indefinite treatment. The present study aimed to assess the anti-inflammatory and antioxidant effects of Carum copticum L. (CC) extract on induced colitis in rats. Methods: Sixty male rats were randomly divided into six groups (n=10 per group). Acetic acid-induced colitis rats were orally administered with doses of 100, 200, and 400 mg/kg CC extract, and 100 mg/kg sulfasalazine for seven consecutive days, respectively. Colonic biopsies were taken to measure histopathological parameters as well as the tumor necrosis factor (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH). Data analysis was performed using the one-way ANOVA and Tukey’s test for normally distributed data. Kruskal-Wallis test followed by Dunn’s test was used for non-normally distributed data. The analysis was performed at P≤0.05 using SigmaStat software (version 10.0). Results:The control colitis group had a significantly higher total colitis index (P=0.01), TNF-α (P=0.01), IL-6 (P=0.01), MPO (P=0.01), and MDA (P=0.01); and lower GSH (P=0.01) than those of the sham group. The colitis group receiving a dose of 200 mg/kg/day CC extract had a significantly lower total colitis index (P=0.01), TNF-α (P=0.01), IL-6 (P=0.01), MPO (P=0.01), and MDA (P=0.01); and higher GSH (P=0.01) than those of the control colitis group. The colitis group receiving a dose of 200 mg/kg/day CC extract had a significantly lower total colitis index (P=0.04), TNF-α (P=0.03), IL-6 (P=0.04), MPO (P=0.03), and MDA (P=0.03); and higher GSH (P=0.01) than those of the colitis group receiving sulfasalazine. Conclusion: The present study revealed that CC extract had healing effects on colitis, possibly due to its antioxidant and anti-inflammatory properties.

Biochemical, histopathological and histochemical effects of Vitis vinifera L extract on acetic acid-induced colitis.

Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate the possible ameliorative effects of the aqueous extract of Vitis vinifera L seed in experimentally induced UC in mice. Materials and Methods: Twenty-four male mice, weighing 25-30 g, were randomly divided into four equal groups. UC-induced by 3% acetic acid and oral doses of Vitis vinifera L seed extract, 150 and 250 mg/kg, and negative control groups were given normal saline. On day 5, intestinal histopathology and body weight changes, ALT, AST, ALP, electrolyte profile plus oxidative stress markers were assayed. Results: Intra-rectal administration of 3% acetic acid caused elevation of serum levels of ALT, AST, ALP, and a decrease in the other parameters such as colonic glutathione level (GSH), catalase enzyme activity. Treatment with Vitis vinifera L seed extract for 5 days showed a significant increase in the body weight of mice was seen in the group given treated with Vitis vinifera L seed extract 250 mg/kg orally compared with colitis control group during the experimental period. An increase in GSH and catalase activity in response to oral treatment with Vitis vinifera L seed extract was observed 5 days after treatment. Histological alterations and loss of polysaccharides content observed due to induced colitis and were compensated for after treatment with the Vitis vinifera L seed extract. Conclusion: Our results indicate that oral treatment of Vitis vinifera L seed extract can be offered as potential therapeutic agents for UC-induced in mice.

The effect of sodium valproate on acetic acid-induced colitis in rats.

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.

Efficacy of oral administration of lactic acid bacteria isolated from cocoa in a fermented milk preparation: reduction of colitis in an experimental rat model.

We investigated the probiotic potential of lactic acid bacteria (LAB) obtained from cocoa fermentation using an experimental rat model of colitis. Cocoa beans were collected from fermentation boxes every 12 h for 5 days to isolate the microorganisms. Strains were isolated by serial dilution and plating on MRS agar. Gram-positive and catalase-negative rods were subjected to DNA extraction, polymerase chain reaction, and sequencing. Ten strains were randomly pooled and used to prepare a fermented milk drink that was used to treat the experimental colitis. A parallel group was treated with a single strain drink. Serum concentrations of cytokines and IgA, total and differential counts of blood leukocytes, and histological appearance were compared with the untreated control colitis group. Eighty strains of LAB were identified as Lactobacillus fermentum (68) and Lactobacillus plantarum (12). The multi-strain LAB pool significantly reduced the total number of leukocytes. There was a significant reduction in the percentage of neutrophils and monocytes compared with the control colitis group. IFN-γ concentration was downregulated in animals treated with the LAB pool. IL-10 and IgA increased significantly in the group treated with the strains. Histological analysis showed that the LAB pool reduced the inflammatory infiltrate and restored tissue architecture. The group treated with the single strain LAB drink (L. fermentum) showed no signs of inflammation remission. The results confirm the probiotic action of cocoa-derived LAB in the treatment of experimental colitis. Studies using isogenic models and humans will clarify the mechanisms of immune response modulation in inflammatory bowel disease.

Intake of Passiflora edulis leaf extract improves antioxidant and anti-inflammatory status in rats with 2,4,6-trinitrobenzenesulphonic acid induced colitis

The antioxidant and anti-inflammatory effects of the aqueous extract of Passiflora edulis leaves, which is a source of vitexin, isovitexin and isoorientin, was investigated in a 2,4,6-trinitrobenzenesulphonic acid induced colitis model. The oral intake of P. edulis extract (1100 µg mL−1) improved significantly (P < 0.05) the endogenous antioxidant status and decreased lipid peroxidation in serum, liver, and colon. The consumption of P. edulis extract decreased the level of pro-inflammatory in colon tissue, especially by reducing IL-1β five-fold and TNF-α two-fold compared to the control colitis group. The extract of P. edulis leaves possessed therapeutic activity in healthy rats and in TNBS-induced colitis, especially by controlling the oxidative stress and inflammation observed in this disease.

Antiinflammatory effect of phytosterols in experimental murine colitis model: prevention, induction, remission study.

Phytosterols, besides hypocholesterolemic effect, present anti-inflammatory properties. Little information is available about their efficacy in Inflammatory Bowel Disease (IBD). Therefore, we have evaluated the effect of a mixture of phytosterols on prevention/induction/remission in a murine experimental model of colitis. Phytosterols were administered x os before, during and after colitis induction with Dextran Sodium Sulfate (DSS) in mice. Disease Activity Index (DAI), colon length, histopathology score, 18F-FDG microPET, oxidative stress in the intestinal tissue (ileum and colon) and gallbladder ileum and colon spontaneous and carbachol (CCh) induced motility, plasma lipids and plasma, liver and biliary bile acids (BA) were evaluated. A similar longitudinal study was performed in a DSS colitis control group. Mice treated with DSS developed severe colitis as shown by DAI, colon length, histopathology score, 18F-FDG microPET, oxidative stress. Both spontaneous and induced ileal and colonic motility were severely disturbed. The same was observed with gallbladder. DSS colitis resulted in an increase in plasma cholesterol, and a modification of the BA pattern. Phytosterols feeding did not prevent colitis onset but significantly reduced the severity of the disease and improved clinical and histological remission. It had strong antioxidant effects, almost restored colon, ileal and gallbladder motility. Plasmatic levels of cholesterol were also reduced. DSS induced a modification in the BA pattern consistent with an increase in the intestinal BA deconjugating bacteria, prevented by phytosterols. Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects.

Modulating effect of Biophytum sensitivum extract on rats with acetic acid-induced ulcerative colitis

Context: Traditionally, Biophytum sensitivum (L.) DC (Oxalidaceae) is used in Indian medicine to treat diseases include stomachache, convulsions, cramps, inflammation, and ulcer.Objective: The present study examines the effect of aerial parts of B. sensitivum (methanol extract) on a murine model of ulcerative colitis (UC).Materials and methods: UC was induced by intracolonic injection of 3% acetic acid in Wistar rats. B. sensitivum (50 or 100 mg/kg b wt) or reference drug sulfasalazine (100 mg/kg b wt) was administrated intra-peritoneally for 5 consecutive days before induction of colitis.Results: In the present study, we demonstrated for the first time that the administration of B. sensitivum (50 mg/kg b wt) was found to inhibit colitis by lowering macroscopic score (up to 3.66 ± 0.77) and also showed significant reduction (p < 0.01) in lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activities. Furthermore, a significant reduction (p < 0.01) in mucosal content of lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) confirms that B. sensitivum could significantly inhibit colitis. The study showed significant reduction (p < 0.01) in colonic tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β), and IL-6 levels as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) after treatment compared with the colitis control group. The histopathological study also confirms the foregoing findings. Treatment with B. sensitivum was also able to inhibit the activation and translocation of transcription factors, nuclear factor (NF)-κB subunits (p65/p50).Conclusion: These results suggest that B. sensitivum exhibits protective effect against acetic acid-induced UC.