Acetic Acid-induced Colitis Research Articles

Phytochemical Screening and Antioxidant Activity of Uncaria tomentosa Extract

Background: Uncaria tomentosa is a traditional medicinal herb with antiviral, antioxidant, immunostimulating, anti-inflammatory, and anticancer effects. Objective: The present study was conducted to evaluate the antioxidant capacity in vitro and in vivo and the phytochemical analysis of Uncaria tomentosa. Materials and Methods: The plant extract was screened for phytochemical compounds and antioxidant capacity in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and in vivo using acetic acid-induced colitis. Colitis was induced in rats by transrectal administration (5 mL/kg) of 4% (v/v) acetic acid. Forty adult albino rats were divided into four groups: control group, acetic acid group, acetic acid + sulfasalazine (100 mg/kg/day) group, and acetic acid + Uncaria tomentosa extract (250 mg/kg/day) group. After inducing colitis, sulfasalazine and Uncaria tomentosa extract were given orally for 10 days. Data were statistically analyzed, and P < 0.05 was considered statistically significant throughout the study. Results: Preliminary phytochemical study showed that Uncaria tomentosa extract contains flavonoids, phenols alkaloids, saponin, and terpenoids. In the DPPH assay, the extract exhibited considerable antioxidant capacity in a dose-dependent manner. Also, Uncaria tomentosa extract dramatically decreased oxidative stress parameters, such as myeloperoxidase enzyme activity and malondialdehyde in colonic tissue. Moreover, Uncaria tomentosa treatment attenuated macroscopic colonic scores and histopathological changes induced by acetic acid. Conclusion: The findings of this study show that Uncaria tomentosa extract could be a source of natural antioxidants and may have a therapeutic effect on ulcerative colitis.

Protective effect of Melissa officinalis against acetic acid-induced ulcerative colitis in rat models: an experimental study.

Inflammation and oxidative activities within the gut play major roles in the pathogenesis of ulcerative colitis (UC). We aimed to determine the effect of Melissa officinalis, an antioxidant and anti-inflammatory agent, on the colon histological characteristics in acetic acid (AA)-induced UC in rat models. Thirty-six male rats with AA-induced colitis were divided into 5 groups: no treatment (AA); daily treatment with 300 mg/kg Melissa officinalis orally (MO) and rectally (MR); and 100 mg/kg mesalamine orally (AO) and rectally (AR). Macroscopic and histopathological evaluation of the colon, along with a biochemical laboratory evaluation, were performed 10 days after UC induction. All treatment groups demonstrated lower macroscopic grading scores compared to the AA group. After treatment with MO, 42.9% of cases demonstrated no macroscopic changes, while 14.3% demonstrated only mucosal erythema. In the MR group 28.6% of rats had no changes in their mucosal lining and 28.6% had only mucosal erythema. Following histopathological evaluation, the AO group had lower scores regarding the severity of ulcer, inflammation, destruction, crypt abscess, and disorganization compared to the MO group. (P=0.02) The MR group demonstrated lower microscopic scores compared to the MO group, and also lower macroscopic scores compared to the AR group, although not significantly (P>0.05). Both oral and topical administration of Melissa officinalis have satisfactory healing properties compared to mesalamine, with topical route having better results. Therefore, further studies are needed to establish the benefit of Melissa officinalis administration (both orally and topically) within a UC treatment protocol.

Apigenin and Exposure to Low Dose Gamma Radiation Ameliorate Acetic Acid-Induced Ulcerative Colitis in Rats.

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

Evaluation of oral and topical bovine colostrum compared to mesalamine in the treatment of animal model of acetic acid-induced ulcerative colitis.

Oxidative activity and inflammatory responses have been shown to play a pivotal role in the pathogenesis of ulcerative colitis (UC). Colostrum is a natural product with anti-inflammatory and antioxidative properties. UC was induced in 37 Sprague Dawley rats by administration of a 2 mL enema of 3% acetic acid (AA). The control groups received no treatment during the study, while the experimental groups received either oral or rectal administration of 100 mg/kg 5-aminosalicylic acid, or oral or rectal administration of 300 mg/kg of colostrum. Histopathological and serological analyses were performed 7 days following treatment. A significant decrease in weight was seen in all rats except for the test groups receiving colostrum (P<0.001). After treatment, the level of superoxide dismutase increased more significantly in the test groups that received colostrum (P<0.05). All test groups had a reduction in C-reactive protein and white blood cell levels. The colostrum test groups also showed a decrease in inflammation rate, ulceration, destruction, disorganization, and crypt abscess of the colonic mucosa. The findings of this study show that the administration of colostrum can improve the pathological changes of the intestinal mucosa, as well as inflammatory responses, in animal models of UC. Further studies at both preclinical and clinical levels are suggested to confirm these findings.

An improved method for experimental induction of ulcerative colitis in Sprague Dawley rats

Ulcerative colitis (UC) is a chronic inflammatory manifestation of the human colon that is linked with colorectal cancer. Development of an appropriate animal model is crucial to study the immunopathophysiology of UC wherein chemical induction is the most popular method of choice. However, unavailability of an optimum experimental model limits the success of this method. The present study aims to establish an optimized model for acetic acid-induced colitis in Sprague Dawley rats. Response Surface Methodology (RSM) with a six-factors Box-Behnken design was employed to generate an improved method of inducing UC in rat, predicting the case statistics, apposite investigation of quadratic response surfaces, and construction of a second-order polynomial equation. UC was diagnosed through three responses viz. weight loss, severity of diarrhea, and appearance of blood in the stool. Analysis of variance alongside RSM jointly revealed that induction of UC can be achieved with highest probability using the combination of parameters that includes 120 gm body weight, 1.5 ml of 4% acetic-acid v/v in distilled water with a single dose of treatment for 24 h including a pre-induction of 5 mins. This optimized UC-induction model was validated in-vivo through disease scoring index and hematological assessments with satisfactory level of desirability.•An improved experimental method for inducing ulcerative colitis (UC) in Sprague Dawley rats has been developed.•Box-Behnken Design-fitted Response Surface Methodology (RSM) was implicated in optimizing the experimental parameters for generating UC.•This statistically optimized and experimentally validated method resembles the recipe for the generation of UC in animal model with the highest possible desirability.

Role of Bifidobacterium infantis in the Treatment of Duodenal and Colon Inflammation in Induced Ulcerative Colitis

&#x0D; &#x0D; &#x0D; &#x0D; This study aimed to investigate the potential protective role of Bifidobacterium (B.) infantis in alleviating ‎‎induced duodenal and colon inflammation associated with ulcerative colitis (UC). Female albino Wister rats ‎‎(n=24) ‎were randomized into four experimental groups: Control Negative, acetic acid-induced colitis (AA colitis), ‎B. infantis-treated (Bifido), orally gavaged with 1 mL of reference strain ‎B. infantis at 108 CFU/mL for four weeks prior to the induction of colitis,‎ and Bifido+AA ‎colitis. Colitis was induced via ‎intrarectal administration of 4% AA solution‎. Seven days post-colitis induction, blood samples were ‎obtained to assess protein levels, and histopathological evaluations were conducted on duodenal and ‎colon tissues. ‎Additionally, immunohistochemical assessments for B-cell lymphoma 2‎ (Bcl-2) in colon and ‎myeloperoxidase (MPO) in duodenum ‎sections were performed‎. Results revealed that B. infantis treatment significantly elevated serum albumin and total ‎protein levels in the Bifido and Bifido+AA colitis groups, approximating those in the Control Negative group. Histopathological and morphological changes of duodenum in AA colitis revealed ulceration of the mucosal epithelium, submucosal inflammatory cellular infiltration, tissue depression resulting in villus atrophy, and crypt hyperplasia. Additionally, ‎colonic crypt gland atrophy and goblet cells depletion were observed. Most of these changes were ameliorated in the Bifido and Bifido+AA colitis groups. Immunohistochemical analysis displayed marked immunopositivity ‎ of Bcl-2 in colon and MPO in duodenum sections of the Bifido and Bifido+AA colitis groups, indicating the antiapoptotic and anti-inflammatory roles of B. infantis. This study demonstrates that B. infantis exerts a protective effect against AA-induced UC by normalizing serum protein levels, ameliorating histopathological alterations, and ‎modulating apoptotic and inflammatory markers. These findings underscore B. infantis as a ‎promising therapeutic agent for UC and warrant further research to elucidate the underlying ‎molecular mechanisms.&#x0D; &#x0D; &#x0D; &#x0D;

Effect of SKB-Gutbiotic on acetic acid induced ulcerative colitis in male Wistar rats

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation gaining increasing attention as it affects considerable number of humans. IBD is reported as ulcerative colitis (UC) and Crohn's disease (CD) Conventional therapies currently available are not satisfactory. Therefore, here, we investigated the effect of SKB-Gutbiotic on acetic acid induced ulcerative coltis (UC) in male Wistar rats. Male Wistar rats, 200-250 g were divided into six groups as follows: Gr. I (control) received 10 mL/kg of distilled water for 21 consecutive days. Gr. II received 2 mL of 4% acetic acid solution once intra rectally for induction of colitis. Gr. III received 2 mg/kg prednisolone as standard control. Groups IV, V &amp; VI were treated with SKB-Gutbiotic @2×109, 20×109 and 50×109 Cfu/kg, respectively. All the animals from each group were sacrificed 24 h after the induction of colitis. Disease activity index, macroscopical damage, hematological parameters, level of superoxide dismutase (SOD), myeloperoxidase (MPO), reduced glutathione (GSH) and histopathological alterations were evaluated. Acetic acid-induced colitis significantly caused alteration in disease activity index, macroscopical damage, MPO and GSH levels (P &lt;0.05) as compared to control group. SKB-Gutbiotic (20×109 and 50×109 Cfu/kg) administration significantly decreased disease activity index, MPO, SOD, increased GSH levels (P &lt;0.05) as compared to colitis rats. In conclusion, SKB-Gutbiotic (20×109 and 50×109 Cfu/kg) significantly showed protective effects against acetic acid-induced colitis as a consequence of its anti-inflammatory and antioxidative properties.

Sanguinarine protects against indomethacin-induced small intestine injury in rats by regulating the Nrf2/NF-κB pathways.

In recent years, small intestine as a key target in the treatment of Inflammatory bowel disease caused by NSAIDs has become a hot topic. Sanguinarine (SA) is one of the main alkaloids in the Macleaya cordata extracts with strong pharmacological activity of anti-tumor, anti-inflammation and anti-oxidant. SA is reported to inhibit acetic acid-induced colitis, but it is unknown whether SA can relieve NSAIDs-induced small intestinal inflammation. Herein, we report that SA effectively reversed the inflammatory lesions induced by indomethacin (Indo) in rat small intestine and IEC-6 cells in culture. Our results showed that SA significantly relieved the symptoms and reversed the inflammatory lesions of Indo as shown in alleviation of inflammation and improvement of colon macroscopic damage index (CMDI) and tissue damage index (TDI) scores. SA decreased the levels of TNF-α, IL-6, IL-1β, MDA and LDH in small intestinal tissues and IEC-6 cells, but increased SOD activity and ZO-1 expression. Mechanistically, SA dose-dependently promoted the expression of Nrf2 and HO-1 by decreasing Keap-1 level, but inhibited p65 phosphorylation and nuclear translocation in Indo-treated rat small intestine and IEC-6 cells. Furthermore, in SA treated cells, the colocalization between p-p65 and CBP in the nucleus was decreased, while the colocalization between Nrf2 and CBP was increased, leading to the movement of gene expression in the nucleus to the direction of anti-inflammation and anti-oxidation. Nrf2 silencing blocked the effects of SA. Together our results suggest that SA can significantly prevent intestinal inflammatory lesions induced by Indo in rats and IEC-6 cells through regulation of the Nrf2 pathway and NF-κBp65 pathway.

Coumaric acid ameliorates experimental colitis in rats through attenuation of oxidative stress, inflammatory response and apoptosis.

Due to the high side effects of commonly used drugs and according to the pharmacological properties reported for coumaric acid (CA), this study was designed to determine the impact of CA on acetic acid-induced colitis in rats, considering its possible anti-inflammatory, antioxidant, and anti-apoptotic properties. Forty-eight male Wistar rats were divided into 6 equal groups (n = 8). Colitis was induced by acetic acid intrarectally. CA in three different doses (50, 100, and 150mg/kg) was administrated for 5days. Finally, the macroscopic and histopathological changes in the colon tissue were examined. The expression of inflammatory and apoptotic genes, including NF-κB, TNF-α, INOS, IL-1β, IL-6, TLR4, Caspase-3, Caspase-8, Bax, Bcl-2 was assessed. In addition, changes in the levels of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), nitrite, and total antioxidant capacity (TAC) were measured in the colon tissue. Colitis led to a decrease in TAC and the activity levels of CAT and SOD and an increase in the expression of inflammatory and apoptotic genes, MDA, and nitrite levels in the colon. Colitis was also associated with edema and severe damage to the epithelium, infiltration of inflammatory cells, and the presence of ulcers and necrosis in the colon tissue. CA significantly improved the inflammation, oxidative stress, apoptosis, and histopathological indices caused by acetic acid-induced colitis on the colon. It is concluded that CA probably exerts its positive effects in the management of colitis, through its anti-inflammatory, antioxidant, and anti-apoptotic properties.

Chelerythrine Ameliorates Acetic Acid-Induced Ulcerative Colitis via Suppression of Inflammation and Oxidation

The incidence of ulcerative colitis (UC), an inflammatory bowel disease (IBD), is drastically increasing globally, leading to greater economic hardship and patient morbidity. This study evaluated the effects of chelerythrine on acetic acid (AA)-induced UC in a mouse model. Mice received chelerythrine (25, 50, and 100 mg/kg, i.g.) and sulfasalazine (SASP) (500 mg/kg, i.g.) for 7 consecutive days following the induction of colitis via the intrarectal administration of AA (5% v/v). Disease activity index (DAI), tissue morphology, tissue damage, oxidative stress (OS), and inflammatory markers were then evaluated. The results revealed that the colonic levels of total antioxidant capacity (T-AOC), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) had decreased, while colonic myeloperoxidase (MPO), malondialdehyde (MDA), lipid peroxide (LPO) activity, colonic and serum interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) levels, and serum lactate dehydrogenase (LDH) had all increased significantly in the colitis untreated group compared to that of the normal control. Treatment with chelerythrine considerably improved most of these parameters, and a dose of 100 mg/kg, was found to be comparable to that of 500 mg/kg SASP. This alkaloid also markedly reversed body weight (BW), clinical activity score, gross lesion score, mucosal edema, and colon weight/length in a dose-dependent manner. In conclusion, the protective effect of chelerythrine could be attributed to its anti-inflammatory and antioxidant activities.

The effect of montelukast, a leukotriene receptor antagonist, on the acetic acid-induced model of colitis in rats: Involvement of NO-cGMP-KATP channels pathway.

Inflammatory bowel disease is a chronic autoimmune disorder that may involve entire gastrointestinal tract. The leukotrienes have a role as mediators in the pathophysiology of colitis. Here, we investigated the effect of a leukotriene receptor antagonist, montelukast, and also the role of the NO-cGMP-KATP channel pathway in acetic acid-induced colitis. Rectal administration of acetic acid (4%) was used for induction of colitis in rats. To investigate our hypothesis, the rats were intraperitoneally pre-treated with L-NAME (NOS inhibitor), L-arginine, sildenafil, methylene blue, glibenclamide, or diazoxide 15 min before treatment with montelukast (5–20 mg/kg, i. p.), for three consecutive days. Then, microscopic, macroscopic, and inflammatory parameters were evaluated. Montelukast reduced the microscopic and macroscopic damage induced by acetic acid. Montelukast also reduced the level of IL-1β and TNF-α. We also showed that the effects of montelukast were significantly attenuated by L-NAME, methylene blue (guanylate cyclase inhibitor), and an ATP-sensitive potassium channel blocker (glibenclamide). Also, the administration of L-arginine, sildenafil, and diazoxide before montelukast produced protective effect. In conclusion, the pathway of the NO-cGMP-KATP channel is involved in the protective effect of montelukast in acetic acid-induced colonic tissue damage.

Influence of laboratory-controlled ethanolic wheatgrass extract on acetic acid-induced changes in biochemical and antioxidant indices in the colitis of Wistar rats

Introduction and Aim: Triticum aestivum (wheatgrass) is a good source of mineral nutrients and antioxidant enzymes. It also acts as a detoxifying agent and helps to revive healthy cells. The present study aimed to assess the effects of acetic acid on biochemical and antioxidant indices in the colitis of Wistar rats using an ethanolic extract derived from the dried shoots of wheatgrass maintained under specified growth conditions.&#x0D; &#x0D; Materials and Methods: Aqueous and ethanolic extract of wheatgrass was subjected to preliminary phytochemical screening and in-vitro antioxidant activity. Effects of the ethanolic wheatgrass extract were investigated in the acetic acid-induced rat colitis model. Sulphasalazine was used as the standard anti-inflammatory drug. Malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidant capacity (TAC), catalase (CAT), and reduced glutathione (GSH) levels were estimated in the rat blood. Colitis was quantified with a clinical score and colon length/weight index was measured. Histopathological analyses were also performed on the colon tissue of rats.&#x0D; &#x0D; Results: The presence of phytochemical elements such as saponins, tannins, alkaloids, and terpenes in aqueous and ethanolic wheatgrass extract was discovered. These compounds have the potential to boost antioxidant and anti-inflammatory effects. The ethanolic extract significantly reduced MDA, MPO, and antioxidant levels (TAC, CAT, and GSH) in colon tissue and blood. Biochemical measurements corroborated the conclusions of histopathological investigation.&#x0D; &#x0D; Conclusion: According to macroscopic, microscopic, histological, and other biochemical studies, ethanolic wheatgrass extract significantly inhibits experimental colitis in rats.

Anxiolytic and anti-colitis effects of Moringa oleifera leaf-aqueous extract on acetic acid-induced colon inflammation in rat

Moringa oleifera decoction is believed to alleviate gastrointestinal tract diseases. This study investigated antioxidant and anxiolytic activities of its leaves aqueous extract on acetic acid-induced colitis in rats. Rats (36) were randomly divided into six groups and received (20 days) distilled water, 10 mL/kg; Moringa oleifera leaf-aqueous extract (25, 50, and 100 mg/kg) or Loperamide (5 mg/kg). On days 1, 8, 17, and 20, behavioral parameters were evaluated. Colitis was induced (day 15, except in normal group) through acetic acid (4%, 1 mL) intra-rectal administration. After sacrifice (day 21), lesion number, weight/length ratio of the colon were recorded. Oxidative stress biomarkers were evaluated. On day 20, Moringa oleifera (100 mg/kg) reduced the number of head dipping and the duration in opened arms, respectively 2.00 ± 0.37 and 5.00 ± 0.37 s against 14.50 ± 0.72 and 2.17 ± 0.48 s in the control. It decreased colon weight/length ratio: 112.29 ± 9.46 against 185.93 ± 5.28 mg/cm in the control; malondialdehyde level (P < 0.01) and nitric oxide concentration (P < 0.001), in the brain: respectively 25.60 ± 0.60 and 36.34 ± 1.19 against 34.00 ± 0.33 and 46.17 ± 3.25 µmol/mg of tissue in the control. In the serum, the extract (50 mg/kg) significantly (P < 0.05) increased the catalase activity (0.10 ± 0.00 against 0.03 ± 0.00 µmol/mg of protein in the negative control group). At 100 mg/kg, it increased (P < 0.001) reduced glutathione concentration to 5.07 ± 0.31 against 3.26 ± 0.08 µmol/mg of protein in the negative control group. The improvement on colitis pathophysiology, the antioxidant and the anxiolytic effects noted therefore suggest that Moringa oleifera can be a potential source of drugs alleviating anxiety and oxidative stress associated to ulcerative colitis.

The effect of combining basil seeds and gum Arabic on the healing process of experimental acetic acid-induced ulcerative colitis in rats

Background & aimUlcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum that oxidative stress and severe inflammation are the main features of this disease. Previous studies have shown that separate consumption of basil and gum arabic can reduce inflammation and oxidative stress. The aim of the study was evaluating the effect of treatment with basil seeds given together with gum arabic on healing, inflammation and oxidative stress in the course of experimental colitis in rats. Experimental procedureA total number of 50 male rats were used, randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with 4% solution od acetic acid. Four days after induction of colitis, rats were treated for next 4 days with saline or combination of basil seeds plus gum arabic (1 mg/kg) or sulfasalazine (100 mg/g) rectally. The experiment was terminated after last dose of treatment. Rats without induction of colitis were used as a sham group. ResultsAcetic acid-induced colitis increased the macroscopic and histopathological damage scores of the colon as well as colon levels of MDA(Malondialdehyde), MPO(Myeloperoxidase), TNFα(Tissue necrosis factor α), IL6 (Interleukin 6)and IL17(Interleukin 17) and decreased SOD(Superoxide Dismutase), GPx (Glutathione Peroxidase) and IL10 (Interleukin 10) levels compared with the control group(P < 0.001). Treatment with basil and gum arabic reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, MDA, MPO, TNFα, IL6(P < 0.001) and IL17 (P < 0.01) levels of the colon and increased SOD, GPx and IL10 levels compared to the colitis group (P < 0.01). ConclusionRectal administration of combination of basil seeds plus gum arabic after induction of colitis, exhibits antioxidant and anti-inflammatory effects, and accelerates the healing of the colon in experimental colitis evoked by acetic acid.

Mesenchymal Stem Cells for the Treatment of Acetic Acid-Induced Ulcerative Colitis in Rats

Background: Ulcerative colitis (UC) is an autoimmune inflammatory bowel disease, characterized by chronic and relapsing inflammation of the intestinal mucosa. Clinical treatments fail to reduce inflammation and induce side effects in nearly 30% of patients. Mesenchymal stem cells (MSCs) are immunomodulatory agents that can encourage tissue repair and regeneration.&#x0D; Aim: To investigate the ability of MSCs to differentiate into enterocytes under the mediation of activin a, fibroblastic growth factor 2, and epidermal growth factors and to study the effect of administering MSCs to rats with acetic acid (AA)-induced UC.&#x0D; Methods: MSCs isolated from the umbilical cord were induced to differentiate into enterocytes. The induced cells were morphologically evaluated by flow cytometry and immunocytochemistry. Forty rats were divided into four groups: control, AA-induced UC, differentiated, and undifferentiated MSC treated groups. The acute UC in rats was induced by 3% AA transrectal administration. Body weight changes, disease activity index (DAI), and histopathological and immunohistochemical CD105 and CD34 staining were recorded. IL-17, IL-10, and TGF- β levels were measured as well.&#x0D; Results: In Both differentiated and undifferentiated MSCs, induced MSCs improved the DAI score and significantly recovered the pathological changes. The favorable effect of MSCs was significantly linked to CD105 overexpression and CD34 low expression. IL-10 and TGF-β levels increased while IL-17 levels decreased.&#x0D; Conclusion: Both differentiated and undifferentiated MSCs showed anti-inflammatory and immunomodulatory effects in our study. Based on our results, MSCs could become potentially useful for regenerative medicine and the clinical treatment of UC.

Evaluation of anti-inflammatory effects of leaf and seed extracts of Plantago major on acetic acid-induced ulcerative colitis in rats

Ethnopharmacological relevancePlantago major (P. major) has traditionally been used in Iranian Persian medicine to treat gastrointestinal ulcers and bleeding. Research objectivesThis study aimed to investigate the anti-inflammatory effects of the leaf and seed extracts of P. major in rats with acetic acid-induced ulcerative colitis (UC). Materials and methodsTo this end, 49 rats were randomly divided into seven groups. UC was induced in all groups but the control (vehicle) group using a single intra-rectal administration of 2 ml of 4% acetic acid. Other groups received daily intraperitoneal (i.p.) injections of the seed extract of P. major (400 mg/kg and 700 mg/kg), the leaf extract of P. major (400 mg/kg and 700 mg/kg), and sulfasalazine (400 mg/kg) for seven consecutive days, respectively. The rats’ rectum was surgically removed and evaluated for macroscopic and microscopic damage. The tissue levels of oxidative stress and inflammatory markers were measured using the ELISA method. ResultsThe high-dose leaf extract significantly decreased ulcer index and histopathologic damage as well as the tissue levels of IL-6, TNF-α, PGE2, IL-1β, MPO, and MDA compared to the damage group. The low-dose leaf extract also significantly reduced the levels of some markers. The seed extract in the two used doses caused a modest decrease in the histopathological damages and ulcer index. ConclusionsP. major leaf extract effectively reduces inflammation and mucosal damage in rats with UC, especially when administered in high doses. P. major seed extract has minimal protective effects on UC.

Rhinacanthus nasutus and okara polysaccharides attenuate colitis via inhibiting inflammation and modulating the gut microbiota.

Plant polysaccharides have prebiotic properties for gut microbiota and immune modulation. This study aimed to investigate the prevention abilities of edible Rhinacanthus nasutus polysaccharide (RNP) and okara polysaccharide (OP) in Sprague-Dawley rats with acetic acid-induced colitis. The characterizations of RNP and OP were analyzed, including Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, and monosaccharide composition. The prebiotic properties of RNP and OP were determined in vitro. In addition, the pathological features of colon length and inflammatory cytokine levels in acetic acid-induced colitis were improved by intragastric preadministration of RNP and OP for 3 weeks. There was no nephrotoxicity or hepatotoxicity in rats via histopathological assessment after RNP and OP intake. Moreover, the abundance of short-chain fatty acids-producing bacteria (Lachnospiraceae, Lactobacilli, and Prevotellaceae) were increased after RNP supplementation. In conclusion, intragastric gavage of RNP and OP significantly modulated the gut microbiota and immune response, consequently alleviating the symptoms of colitis. This novel finding provides an alternative strategy and potential application of these two polysaccharides for colitis prevention and treatment.

A validated LC-MS/MS method for the determination of hederasaponin C: Application to pharmacokinetics-pharmacodynamics studies in the therapeutic area of acetic acid-induced ulcerative colitis in rats.

Hederasaponin C (HSC), one of the main components of Pulsatilla chinensis, is considered as a potential drug for the treatment of inflammatory bowel disease. In the present research, we developed a pharmacokinetics-pharmacodynamics model to describe the concentration-effect course of drug action following the intraperitoneal injection of HSC in colitis rats. A sensitive UPLC-MS/MS method was established for the the determination of HSC in rat plasma to explore the pharmacokinetics properties. The separation was performed on an Accucore C18 column (2.1 × 100 mm, 2.6 μm) with a flow phase consisting of acetonitrile and 0.1% formic acid water. The assay method was validated and demonstrated good adaptability for application in the pharmacokinetics study. Then the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in colon tissues were measured using an ELISA assay. The levels of TNF-α, IL-1β and IL-6 were decreased after HSC administration, suggesting that HSC can significantly improve the level of inflammatory syndrome factor. The pharmacokinetics study showed that the time to peak concentration of HSC was 1 h. The concentration-effect curves showed a hysteresis loop. There was also a hysteresis between the peaked concentration and the maximum effect of HSC. The present study established in vivo pharmacokinetics-pharmacodynamics models and the results showed a great potential of HSC for treating ulcerative colitis.

The Hydro-alcoholic Extract of Achillea wilhelmsii C. Koch Ameliorates Acetic Acid-induced Ulcerative Colitis through TLR-4

The Hydro-alcoholic Extract of Achillea wilhelmsii C. Koch Ameliorates Acetic Acid-induced Ulcerative Colitis through TLR-4

Formulation, Standardization, and Preclinical Evaluation of Polyherbal Suspension against Inflammatory Bowel Disease

The pharmacological healing for inflammatory bowel diseases continues to be uncertain and requires immediate therapeutic interventions. A poly-herbal formulation obtained from a traditional and authentic classic text of Ayurveda was assessed for its effect against IBD (inflammatory bowel disease) in this study. The formulated poly-herbal suspension comprises three different drugs namely, Burma dhaniya (Eryngium foetidum), Sapota (Manilkara zapota), and Curry leaves (Murraya koenigii). The formulated suspension was evaluated for certain standard parameters like organoleptic and accelerated stability studies at various temperatures. It was checked for its efficacy by oral route in acetic acid-induced colitis affected Balb/c mice. Mice were orally administered with formulated suspension (275 mg/kg, 550 mg/kg,), every 24 hours for 10 days. Histopathology, macroscopic damage score, myeloperoxidase (MPO) activity, and red blood cell parameters were evaluated after treatment. Reduction in the MPO activity, decrease in the macroscopic damage scores, and an increase in RBC cell count were seen distinctly at a high dose of 550 mg/Kg. The results obtained, established the effectiveness of the poly-herbal suspension against inflammatory bowel disease by treating the mice from acetic acid-induced colitis by reducing inflammation and oxidative damage to the colon. The maximum therapeutic effective activity was found to be 550 mg/kg for IBD mice.