Rat Model Of Ulcerative Colitis Research Articles

Tonifying-Qi-and-Detoxification Decoction attenuated injuries of colon and lung tissues in ulcerative colitis rat model via regulating NF-κB and p38MAPK pathway.

BackgroundTonifying-Qi-and-Detoxification Decoction (TQDD) is a Chinese medicine compound. This research probed the possible protective effects of TQDD on injuries of the colon and lung tissues in ulcerative colitis (UC) rat model.MethodsUC rat model was established by colon mucosal tissue sensitization combined with TNBS-ethanol. Ninety-six rats were randomly divided into normal control (NC), model, sulfasalazine (SASP), and TQDD (low, middle, and high dosages) groups. After 4 weeks intervention, all rats were sacrificed. The microstructure of lung tissue was observed using hematoxylin-eosin (HE) staining. Transmission electron microscope (TEM) was utilized to assess the ultrastructure change of alveolar epithelial type II cells (AEC-II). The mRNA expressions of Bax, Caspase 3, nuclear factor kappa B (NF-κB) and NF-κB inhibitor α (IKBα) in tissues were measured via quantitative reverse transcription PCR (qRT-PCR) assay. Western blotting and immunohistochemistry (IHC) were used to test p38MAPK, activating transcription factor 2 (ATF2), c-jun and c-fos expressions in tissues.ResultsTQDD alleviated microstructure change of lung tissues, lung cell apoptosis and ultrastructure alterations of AEC-II in UC rat model. Moreover, TQDD suppressed activation of NF-κB pathway in colon and lung tissues. Besides, TQDD inhibited p38MAPK pathway in colon and lung tissues, as well as reduced ATF2, c-jun, and c-fos expressions in colon and lung tissues.ConclusionsThis research confirmed the beneficial effect of TQDD on injuries of colon and lung tissues in UC rat model. TQDD attenuated injuries of lung and colon tissues in colon mucosal tissue sensitization combined with TNBS-ethanol-caused UC model via regulating NF-κB and p38MAPK pathways.

Effect of Shenling Baizhu San on Intestinal Flora in a Rat Model of Ulcerative Colitis with Spleen Deficiency and Dampness.

Objective Shenling Baizhu San (SLBZS) is reported as an effective drug for ulcerative colitis (UC); however, its effect on intestinal flora remains unknown. In this study, we investigated the effect of SLBZS on intestinal flora in a rat model of UC with spleen deficiency and dampness. Methods UC was induced in rats using 2,4,6-trinitrobenzene sulfonic acid on the basis of a model of spleen deficiency and dampness. The 16S rDNA sequencing was used to detect structural changes in the intestinal flora; the phylogenetic investigation of communities by reconstruction of unobserved state (PICRUSt) analysis was used to predict the altered pathways. Results Compared with the model group, rats in the SLBZS group exhibited decreased levels of TNF-α(P < 0.05), and increased abundance and diversity of the intestinal flora. The abundance of Actinobacteria (P < 0.001) and Bacteroides (P < 0.01) increased and that of Firmicutes decreased (P < 0.001), and the abundance of Bifidobacterium(P < 0.05) and Allobaculum increased. PICRUSt analysis showed that the altered pathways between the groups were those of fatty acid and antibiotic biosynthesis, amino acid metabolism, and the pentose phosphate pathway. Conclusions SLBZS can regulate the structure and function of the intestinal flora, alter expression levels of certain metabolic pathways, and has the potential to treat UC.

Gut microbiome alterations in colitis rats after moxibustion at bilateral Tianshu acupoints

BackgroundThe pathogenesis of ulcerative colitis (UC) is closely related to the gut microbiota. Moxibustion has been used to improve the inflammation and gastrointestinal dysfunctions in gastrointestinal disorders such as UC. In this study, we investigated whether moxibustion could improve the gut microbial dysbiosis induced by dextran sulphate sodium.MethodsTwenty-five male rats were randomly assigned into five groups. The UC rat model was established by administering DSS solution. The rats in the moxibustion and normal rats with moxibustion groups were treated with moxibustion at Tianshu (bilateral, ST25) points, and the mesalazine group rats were treated with mesalazine once daily for 7 consecutive days. Disease activity index (DAI) and haematoxylin and eosin staining were used to evaluate the effect of moxibustion. Gut microbiota profiling was conducted by metagenomic high throughput sequencing technology. The gut microbiota composition, diversity and function were analyzed and compared using metagenomics methodologies.ResultsThe DAI scores and histopathology scores in the moxibustion and mesalazine groups were significantly decreased compared with the UC group (P < 0.01). Moxibustion treatment increased abundance levels of Bacteroidetes, Actinobacteria, Ascomycota, Synergistetes and decreased abundance of Firmicutes, Proteobacteria. At the genus level, the abundance of Bacteroides, Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2, were increased and Bacteroides_bacterium_H3, Parabacteroides, Porphyromonas, Alistipes, Parasutterella were decreased in the UC group in comparsion with those in the NG group. Moxibustion increased the abundance of Bacteroides and Bacteroides_bacterium_H3 and decreased Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2. In UC group, the specie Bacteroides_massiliensis was negatively (P < 0.05) correlated with IL-23, Bacteroides_eggerthii_CAG109 and Bacteroides_eggerthii were negatively (P < 0.05) correlated with TGF-β. And the species Prevotella_sp_CAG1031 and Bacteroides_bacterium_H2 were significant positively (P < 0.05) correlated with IL-23. In addition, compare with the normal group, genes involved in certain metabolic pathways, such as energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, were under-represented in the UC group, and these changes in the metabolic pathways could be reversed by moxibustion treatment and mesalazine treatment.ConclusionsOur findings suggest that moxibustion treatment may protect the host from mucosal inflammation by modulating the intestinal microbiota community.

Effect of Coptis chinensis franch and Magnolia officinalis on intestinal flora and intestinal barrier in a TNBS-induced ulcerative colitis rats model

BackgroundIn folk medicine Coptis chinensis Franch (Huanglian in Chinese, HL) and Magnoliae officinalis (Houpo, HP) have been used to treat gastrointestinal disorders over hundreds of years, such as ulcers and inflammation. PurposeTo investigate the therapeutic effects of HL and HP on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC) rats, and investigated its effect on the intestinal flora of UC rats. MethodTNBS 40 mg/kg was utilized to establish UC model. Rats were sacrificed after gavage for 7 days. Body weight loss, disease activity index (DAI), colonic mucosal damage index (CMDI) and histopathology were measured. Intestinal content samples were collected, and analyzed by 16 S rRNA sequencing. Western blot, immunohistochemistry and real-time polymerase chain reaction were used to evaluate the regulation mechanism of HL+HP in UC model rats. ResultsThe results showed that the DAI score, CMDI score and histological score were significantly decreased in each group. The symptoms of diarrhea, hematochezia, colonic mucosal injury and congestion and edema were improved. Sequencing results of intestinal flora showed that the abundance of probiotics such as Akkermansia and Blautia was increased in HL group and HL+HP group, while probiotics such as Allobaculum and Alloprevotella were increased in HP group. The intestinal pathogenic bacteria such as Escherichia-Shigella and Clostridium_sensu_stricto_1 were decreased. In addition, HL+HP could also inhibit the inflammatory response and protect the integrity of the tight junction to play an anti-UC effect. ConclusionCoptis chinensis Franch and Magnolia officinalis might prevent intestinal barrier damage by regulating intestinal flora imbalance and inhibit the inflammatory response.

Histological study of the effect of quercetin on experimentally induced ulcerative colitis in adult male albino rats

Background Ulcerative colitis is a huge health problem, and its occurrence is increasing around the world. It is manifested with abdominal pain, diarrhea, bloody stool, and body weight loss. Aim This work aimed to evaluate the possible effects of quercetin on a rat model of ulcerative colitis that was induced by acetic acid. Materials and methods A total of 40 adult male albino rats were used in this study. Rats were divided into controls, that is, group I, which included 10 rats that received intrarectal injection of a single dose of 2 ml of physiological saline, and experimental cases, that is, group II. The experimental group contained 30 rats and were divided into three equal subgroups. Subgroup IIA received 50 mg/kg/day of quercetin orally for three consecutive days, subgroup IIB received intrarectal injection of a single dose of 2 ml of 4% acetic acid solution for ulcerative colitis induction, and subgroup IIC received 50 mg/kg/day of quercetin orally for 3 consecutive days before induction of ulcerative colitis by a single dose of acetic acid that was received by intrarectal injection on the fourth day. Colonic specimens were subjected to histological and immunohistochemical examinations. The data were analyzed statistically. Results The current study of subgroup IIB showed disturbed normal histological architecture of colonic structure, but in subgroup IIC, quercetin resulted in preservation of normal histological architecture of the colon. Conclusion There is a correlation between quercetin and reduction of the severity of acute attacks of ulcerative colitis induced by acetic acid in adult male albino rats. Quercetin leads to protection of colon.

Myrica salicifolia Hochst. ex A. Rich. suppress acetic acid-induced ulcerative colitis in rats by reducing TNF-alpha and interleukin-6, oxidative stress parameters and improving mucosal protection.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with rising prevalence in developing countries, and limited success of current therapies, natural products have immense potential for therapy due to their "disease modifying and side-effect neutralizing" potential. Myrica salicifolia is traditionally used for gastrointestinal diseases and have reported antiinflammatory activities, but its use in IBD has not yet been studied. Therefore, in the present study, the effects of the root extract of M. salicifolia (Ms.Cr) were investigated using the acetic acid-induced UC model in rats. For 6 days, the rats were given either vehicle (10mL/kg), lower (200mg/kg), and higher (400mg/kg) doses of Ms.Cr, or the positive control drug (prednisolone; 2mg/kg) orally. A single dosage of 5% acetic acid (1.0mL) was administered intrarectally to rats on day 6 to induce UC. Disease activity index (DAI), histological observations, the biochemical parameters related to oxidative stress, and specific cytokines such as interleukin-6 (IL-6) and the tumor necrosis factor-α (TNF-α) were determined to assess the effect of Ms.Cr. In comparison to the AA-induced colitis rats, Ms.Cr's pretreatment significantly decreased DAI, colonic ulceration, and inflammatory score. Total glutathione levels and catalase activity were considerably recovered in the colitis group treated with Ms.Cr, whereas enhanced lipid peroxidation in colon tissues was significantly decreased. Moreover, Ms.Cr pretreatment also caused inhibition of the activation of IL-6 and TNF-α in the colonic tissues of respective groups. Based on these findings, Ms.Cr might be developed to treat UC in the future.

Faba beans with enhanced antioxidant activity ameliorate acetic acid-induced colitis in experimental rats.

Faba beans are among the legumes that are of the greatest importance due to their high nutritional value. In addition to the essential nutrients that faba beans contain, they also contain bioactive compounds such as phenolics and flavonoids that are considered as potent natural antioxidants. Ulcerative colitis (UC) is an inflammatory bowel disease in which oxidative stress plays an essential role in the pathophysiology. The aim of the current study was to evaluate the antioxidant activity of faba bean seeds harvested from plants grown from seeds pre-treated with selenium, garlic husk extract and/or lemon peel extract and to evaluate their in vivo effects in a rat model of UC. 54 female rats were divided randomly into nine groups (n = 9). All groups were given the different tested treatments 14 days prior to UC induction using acetic acid (intra-rectal injection of 2 ml, 4% v/v in saline). Our results revealed that the treatment of faba bean seeds with a mixture of selenium, garlic husk extract and lemon peel extract before planting led to a significant increase in selenium, nitrogen, potassium, total protein, phenolic and flavonoid content in the harvested faba bean seeds with a subsequent enhancement of their antioxidant capacity. Consumption of such faba beans showed potential protective and therapeutic effects during experimental colitis by reducing colonic oxidative stress and increasing colonic antioxidant defense mechanisms. Further research is required to understand the mechanisms by which faba beans influence colitis, their effects on various inflammatory biomarkers and their impact on the severity of colitis in humans.

The Protective Effect of Misoprostol on Dextran Sodium Sulphate-Induced Ulcerative Colitis Model in Rats

The Protective Effect of Misoprostol on Dextran Sodium Sulphate-Induced Ulcerative Colitis Model in Rats

Anti-Ulcerative Colitis Activity of the Aqueous Leaves Extract of Khaya Senegalensis in Acetic Acid-Induced Colitis Rat Model

intestinal tract mainly colon. The disease is characterized by diarrhoea, blood in the stool, abdominal pain, and weight loss. Khaya senegalensis a plant commonly called dry zone Mahogany has been used as a remedy for several human gastrointestinal ailments. Objectives: To investigate the effect of aqueous leaves extract of Khaya senegalensis in the acetic acid-induced ulcerative colitis rat model. Study design: Preclinical randomised controlled trial. Methods: extraction was done using water, initial phytochemical screening and oral LD50 were determined. Colitis was induced in rats using 4% acetic acid administered intra rectally. The rats were divided into five groups, group 1 received water, groups 2, 3, and 4 received graded doses of leaves extract while group 5 received prednisolone as the positive control. Symptomatic parameters like the daily stool consistency and appearance and histological parameters such as ulcer area, lesson severity score, ulcer index, weight/length ratio and percentage cure were measured. Results; The leaves extract showed presence of alkaloids, tannins, flavonoids, saponins, steroids, volatile oil etc. The oral LD50 was greater than 5000mg/kg and the efficacy of the 400mg/kg extract administered group was not statistically significantly different from the positive control group that received the standard drug prednisolone. Conclusion: It can be concluded that the aqueous leaves extract of Khaya senegalensis possess significant anti-ulcerative colitis activity on acetic acid-induced ulcerative colitis rat models and appears to be safe.

Benefit Effect of Dendrobium officinale Ultrafine Powder on DSS-Induced Ulcerative Colitis Rats by Improving Colon Mucosal Barrier.

Materials and Methods After intragastric administration of DOFP for 3 weeks, the rat UC model was made by the administration of 4% oral DSS solution for one week, and the drug was given at the same time. During the experiment, the disease activity index (DAI) score of the rats was regularly computed. At the end of the experiment, the blood routine indexes of rats were obtained. The histopathological changes in the colon were monitored by hematoxylin-eosin (H&E) and PAS staining and observation of ultrastructural changes in the colon by transmission electron microscope. Occludin expression in the colon was monitored by Western blot, the expression of claudin-1 and ZO-1 in the colon was detected by immunofluorescence, and the expression of TNF-α, IL-6, and IL-1β in the colon was detected by immunohistochemistry. Results The results firstly indicated that DOFP could significantly alleviate the signs and symptoms of the DSS-induced rats UC model, which manifested as improvement of body weight loss, increase of colon length, and improvement of the symptoms of diarrhea and hematochezia. Then, results from histopathology, blood routine examination, and transmission electron microscope analysis further implied that DOFP could dramatically reduce inflammatory cell infiltration and restore intestinal epithelial barrier integrity. In addition, the experiments of Western Blot analysis, immunofluorescence, and PAS staining also further confirmed that DOFP could markedly increase related protein expressions of the intestinal barrier and mucus barrier, as the expression of occludin, claudin-1, and ZO-1 in the colon significantly decreased. The experiments of immunohistochemistry confirmed that DOFP could markedly decrease protein expression levels of inflammatory cytokines TNF-α, IL-6, and IL-1β. Conclusion DOFP notably alleviated inflammatory lesions, repaired the colon mucosa damage by promoting the expression of tight junction proteins occludin, claudin-1, and ZO-1 and inhibiting the release of inflammatory factors TNF-α, IL-6, and IL-1β, and finally achieved the purpose of treating UC.

The protective effect of Boswellic acid and Ellagic acid loaded, colon targeted, and pH-sensitive N-succinyl chitosan in ulcerative colitis rat model

Targeted drug delivery systems that provide therapeutic activity with lower concentrations of both herbal and other substances, while reducing access to non-target sites and undesirable effects; have an important potential for future projections in terms of pharmacological and toxicological studies. The present study aimed to investigate the protective effects of Acetyl 11-keto-β-boswellic acid (AKBA) and Ellagic acid (EA) loaded, colon targeted, and pH-Sensitive N-succinyl chitosans (NsCh) in ulcerative colitis (UC) model induced by acetic acid (AA) in rats. The physicochemical characterization (elemental analysis, FT-IR, DSC, XRD, SEM, NMR) analyses, swelling, and releasing tests of NsCh's suggested that AKBA and EA were successfully loaded to pH-sensitive polymer and targeted to the colon. The targeted AKBA and EA were administered to Wistar rats (n:30, 5 groups) and damage, inflammatory cytokine, protein expression, oxidative stress, and antioxidant parameter levels in colon tissues of the groups were determined. Increase in the levels of CAT, GPx activities, and decrease in necrosis, inflammation, and levels of MDA, TNF-α, COX-2, NF-kB were observed in the targeted EA and AKBA groups compared to the UC group. The potential protective effect of EA and AKBA loaded, colon-targeted, pH-sensitive controlled releasing system against UC and the potential to be licensed preparations by completing the next stages of in vitro and in vivo studies were demonstrated.

Study of the therapeutic effects of Painong powder on ulcerative colitis and the role of Platycodonis Radix in the prescription based on pharmacodynamic, pharmacokinetic, and tissue distribution analyses

Ethnopharmacological relevanceHerbal formulas have unique efficacy and are of great significance to the theory and practice of Chinese medicine and are therefore gaining increasing attention in research. Painong powder (PNS), composed of Aurantii fructus immaturus (Zhishi in Chinese, ZS), Paeoniae Radix Alba (Baishao in Chinese, BS), and Platycodonis Radix (Jiegeng in Chinese, JG), has remarkable effects on the detoxification and discharge of pus. JG is traditionally used to treat pulmonary carbuncles and is considered a ‘medicinal guide’. According to the composition theory of prescriptions, JG is an ‘assistant and guide’ medicine. The role of JG as an adjuvant has gained increasing attention. Aim of the studyThe study was designed to prove the efficacy of PNS in ulcerative colitis (UC) and to study the role of JG in PNS via pharmacodynamic, pharmacokinetic, and tissue distribution analyses. Materials and methodsFor the pharmacodynamic study, the UC rat model was induced using 5% trinitrobenzene sulfonic acid (TNBS). The results of the macroscopic characterization, histological analysis, and cytokine levels, including those of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB), were integrated to evaluate the treatment of UC with PNS. In addition, an LC-MS/MS method was established and validated to analyze the blood pharmacokinetic parameters and tissue distribution of naringin and paeoniflorin. ResultsAfter the administration of high-dose PNS, the UC rats showed amelioration of macroscopic damage at the lesion site. The cytokine levels in the plasma, colon, and lung tissues were also decreased. The pharmacokinetic parameters showed that compared with UC rats administered with PNS-JG, those administered with PNS showed an increase in the AUC, MRT, and Tmax of naringin and paeoniflorin, and a decrease in their clearance rate. Furthermore, naringin and paeoniflorin had higher concentrations in the colon and lung tissues in the normal and model groups administered with PNS than in those administered with PNS-JG. ConclusionsPNS was shown to have marked therapeutic efficacy against TNBS-induced UC in rats. The effect of JG in PNS was reflected by the differences in the pharmacokinetic parameters and tissue distribution of the active components, providing valuable information for the clinical application of PNS in the treatment of UC. However, knowledge about how JG works as an adjuvant medicine in PNS is still lacking.

Optimization study of combined enteric and time-dependent polymethacrylates as a coating for colon targeted delivery of 5-ASA pellets in rats with ulcerative colitis

Formulation design for colon-specific delivery of 5-aminosalicylic acid (5-ASA) could bring some therapeutic benefits in the treatment of ulcerative colitis (UC).In the current study, a 32 full factorial design was used to predict optimum coating composed of two enteric (poly methacrylic acid, methyl methacrylates 1:2 and 1:1) and time-dependent (poly ethyl acrylate, methyl methacrylate, trimethylammonio ethyl methacrylate chloride 1:2:0.1) polymethacrylates for colon-specific delivery of 5-ASA pellets. A unique coating composition and coating level predicted by the model was applied onto either inulin-free 5-ASA pellets or inulin-bearing 5-ASA pellets and the coated pellets were examined by dissolution test in-vitro. The coated pellets were also tested in a rat model of UC and compared with the a commercially available colonic delivery system of 5-ASA.The ratio of the two enteric polymethacrylates and time-dependet polymethacrylate of 16:64:20 w/w at a coating level of 15% was discovered as the optimum coating for delivery of 5-ASA pellets to the colon. In general, the coated pellets offered a better therapeutic outcome compared to commercially available colonic delivery system of 5-ASA and uncoated pellets in terms of colitis activity index and the colon's tissue enzymes of MDA and GSH.It seems that the coating composed of enteric and pH-dependent polymethacrylates could tune up the rate of drug release from 5-ASA-coated pellets and trigger drug release based on pH and time.

Ameliorative effects of Triphala on mucosal damage in rat model of ulcerative colitis

In Ayurvedic practice, Triphala is widely used in gastric problems including constipation, large intestinal inflammation and colitis. The present research was planned to assess the ameliorative effects of Triphala formulations in reducing the magnitude and severity of ulcerative colitis. Triphala formulations prepared by mixing three fruits, Haritaki (Terminalia chebula), Bibhitaki (Terminalia belerica) and Amlaki (Emblica officinalis) in different ratios i.e., 1:1:1 (Triphala equal) and 1:2:4 (Triphala unequal) as per classical references. Wistar albino rats were administered with two ml of acetic acid (4% v/v) in intra-colonic lumen for induction of colitis. The efficacy of Triphala was measured on various parameters namely, in vivo fluid absorption in tied-off colon, ulcer score and colonic mucosal parameters. The degree of alteration in colonic fluid transport was significantly reversed by Triphala equal, Triphala unequal and sulphasalzine as standard drug. Triphala formulations significantly attenuated the nitric oxide (NO), myeloperoxidase (MPO) and lipid peroxidation (malondialdehyde MDA) levels in mucosa of rat colon. Pre-treatment with Triphala unequal formulation attenuated the severity of the colonic macroscopic damage score, histologic injury and counteracted the depletion of glutathione and superoxide dismutase activity hence, reduced the oxidative stress in colonic mucosa. Triphala unequal formulation has better protective effects. Outcomes of the present study reveal the usefulness of Triphala formulations in attenuating the colonic inflammation in experimental-induced ulcerative colitis.

Moxibustion Inhibits the Expression of Colonic NLRP3 through miR7/RNF183/NF-κB Signaling Pathway in UC Rats.

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

Administration of Nrf-2-Modified Hair-Follicle MSCs Ameliorates DSS-Induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is a common chronic nonspecific intestinal inflammation of unknown etiology associated with a low cure rate and a high relapse rate. Hair follicle mesenchymal stem cells (HF-MSCs) are a class of pluripotent stem cells that have differentiation potential and strong proliferation ability. Nuclear factor red system related factor (Nrf-2) is a key factor in the oxidative stress response. Dextran sulfate sodium- (DSS-) induced rat UC models closely mimic human UC in terms of symptoms and histological changes. Animals were divided into five groups, including a healthy group and UC model rats treated with normal saline, Nrf-2, HF-MSCs, or Nrf-2-expressing HF-MSC group. Based on the expression of intestinal stem cells, inflammatory factors, anti-inflammatory factors, and disease activity index scores, Nrf-2-expressing HF-MSCs had the most obvious therapeutic effect under the same treatment regimen. This study provided a new potential clinical treatment option for ulcerative colitis.

Photodynamic Therapy of Novel Photosensitizer Ameliorates TNBS-Induced Ulcerative Colitis via Inhibition of AOC1.

Ulcerative colitis (UC), a chronic, nonspecific inflammatory bowel disease characterized by continuous and diffuse inflammatory changes in the colonic mucosa, requires novel treatment method. Photodynamic therapy (PDT), as a promising physico-chemical treatment method, were used to treat UC rats’ model with novel photosensitizer LD4 in this paper, the treatment effect and mechanism was investigated. LD4-PDT could improve the survival rate of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC model rats, decrease expression of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), myeloperoxidase (MPO) and increase the expression of glutathione (GSH) and superoxide oxidase (SOD), while protecting the integrity of the intestinal epithelium. LD4-PDT treatment could rebuild the intestinal microflora composition and reprogram the colonic protein profiles in TNBS-induced rats to almost the normal state. Proteomics analysis based upon TNBS-induced UC model rats revealed that Amine oxidase copper-containing 1 (AOC1) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC1 may be a promising target.

Effects of a P2X7 receptor antagonist on myenteric neurons in the distal colon of an experimental rat model of ulcerative colitis.

Inflammatory bowel diseases (IBDs) are chronic diseases of the gastrointestinal tract that include ulcerative colitis and Crohn's disease and affect enteric neurons. Research has shown that Brilliant Blue G (BBG), a P2X7 receptor antagonist, restores enteric neurons following ischemia and reperfusion. This study aimed to evaluate the effect of BBG on myenteric neurons of the distal colon in an experimental rat model of ulcerative colitis. Colitis was induced by injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the large intestine. BBG was administered 1h after colitis induction and for five consecutive days thereafter. Distal colons were collected 24h or 7 days after TNBS injection. The animals were divided into 24-h and 7-day sham (vehicle injection rather than colitis induction), 24-h colitis, 24-h BBG, 7-day colitis and 7-day BBG groups. The disease activity index (DAI), neuronal density and profile of neuronal nitric oxide synthase (nNOS)-, choline acetyltransferase (ChAT)- and P2X7 receptor-immunoreactive enteric neurons were analyzed, and histological analysis was performed. The results showed recovery of the DAI and histological tissue integrity in the BBG groups compared to those in the colitis groups. In addition, the numbers of neurons positive for nNOS, ChAT and the P2X7 receptor per area were decreased in the colitis groups, and these measures were recovered in the BBG groups. Neuronal size was increased in the colitis groups and restored in the BBG groups. In conclusion, BBG is effective in improving experimental ulcerative colitis, and the P2X7 receptor may be a therapeutic target.

Effects of ShenLing BaiZhu San Supplementation on Gut Microbiota and Oxidative Stress in Rats with Ulcerative Colitis.

The aim of this study was to evaluate the effect of gut microbiota and antioxidation of Shenling Baizhu San (SLBZS) as a supplement in a rat model of ulcerative colitis (UC) induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Acute intestinal inflammation was induced in 40 male SD rats aged 4 weeks with 100 mg/kg TNBS, and then three dosages of SLBZS (0.5 g/kg, 1 g/kg, and 1.5 g/kg) were administered for eight days, respectively. Faecal microbiome composition was assessed by 16S rRNA high-throughput sequencing. The result indicated that SLBZS could reduce the diversity of gut microbiota and increased its abundance. At the genus level, the relative abundance of SCFAs producing bacteria including Prevotella and Oscillospira increased, while the relative abundance of opportunistic pathogens including Desulfovibrio and Bilophila decreased. Meanwhile, SLBZS could improve the lesions of colon and significantly reduce the level of MPO, increase the levels of SOD and CAT in rats' serum. These findings revealed that SLBZS was effective and possessed anticolitic activities in a rat model of UC by reducing macroscopical and microscopical colon injury, enhancing antioxidant capacity, and regulating gut microbiota.

MiR-200b-3p alleviates TNF-α-induced apoptosis and inflammation of intestinal epithelial cells and ulcerative colitis progression in rats via negatively regulating KHDRBS1.

Ulcerative colitis (UC) is difficult to be treated. miRNAs are a group of gene regulators. Study demonstrated that miR-200b-3p is involved in the development of UC, but the specific molecular mechanism is still unclear. A UC model was established by injecting acetic acid into rectum of rats, which were then treated with miR-200b-3p antagonists and agonists. Weight change, fecal viscosity and fecal bleeding were measured to determine disease activity index. The ratio of colon length to weight was measured. Colon lesions were detected by H&E staining. ELISA was used to detect the expression of TGF-β in colon tissues and IL-10/CRP in serum. Intestinal epithelial cells (NCM460) were treated by TNF-α to create an inflammatory environment. MRNA and protein levels of miR-200b-3p, KHDRBS1, IL-10, IL-6, IL-1β, TGF-β, Bcl-2, Bax and C-capase-3 were detected by qRT-PCR and Western blot, respectively. TargetScan database and dual-luciferase reporter assay were conducted to predict the targeting relationship between miR-200b-3p and KHDRBS1. MTT and flow cytometry were respectively performed to detect cell proliferation and apoptosis. MiR-200b-3p expression was inhibited, leading to increased disease activity index and colonic length-weight ratio, and aggravation of lesions of the UC rat model. Up-regulation of miR-200b-3p can relieve inflammation and apoptosis of immune cells in UC rats. MiR-200b-3p targeted KHDRBS1 and inhibited its expression. Moreover, KHDRBS1 reversed the effects of miR-200b-3p on apoptosis, proliferation and inflammation of intestinal epithelial cells. MiR-200b-3p alleviates UC by negatively regulating KHDRBS1.