BACKGROUND/AIMS: Ulcerative colitis (UC) is a chronic disease that characteristically has a relapsing and remitting course. Probiotics might possibly induce remission in the treatment of active UC. Aims of our study were to assess the efficacy of VSL#3 on clinical response and colonic tissue cytokine concentration changes in patients with active UC. METHODS: Twenty-four eligible patients with mild to moderate UC received open-label VSL#3 4 sachets daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by ulcerative colitis disease activity score and colonic tissue cytokine profiling done at baseline and at week 8. RESULTS: Twenty-four patients (mean age, 43.7 years; range, 20-70 years; male/female, 15/9) were enrolled and 2 patients did not have the final endoscopic assessment. A total of 22 patients were analyzed. Intent to treat analysis demonstrated remission in 45.8% of subjects (n=11); partial response in 20.8% (n=5); no change or worse in 25.0% (n=6) of subjects. The mean ulcerative colitis disease activity index (UCDAI) scores decreased from 7.09+/-1.81 to 1.45+/-1.29 in patients with a remission (p<0.001). The mean endoscopic scores had also significantly decreased from 1.91+/-0.54 to 0.63+/-0.50 in patients with a remission (p<0.001). The concentrations of colonic cytokines did not change significantly during treatment in patients with a remission. CONCLUSIONS: Our study demonstrated that VSL#3 is effective in achieving clinical responses and remissions in patients with mild-to moderately active UC, further supporting the potential role in UC therapy.
Adult ; Aged ; Colitis, Ulcerative/*therapy ; Cytokines/metabolism ; Drug Administration Schedule ; Humans ; Male ; Middle Aged ; Probiotics/*therapeutic use ; Severity of Illness Index

OBJECTIVETo investigate the therapeutic effect of Baitouweng Decoction on dextran sodium sulphate (DSS)-induced ulcerative colitis in mice and explore its mechanism involving miR-19a.

METHODSForty female c57 mice were randomly allocated into 4 equal groups, namely the normal control group, model group (treated with 3.5% DSS solution), treatment group (treated with DSS+Baitouweng Decoction), and positive control group (treated with DSS+5-ASA). Ulcerative colitis was induced in the mice by feeding them with 3.5% DSS in drinking water, and the mice in the control group were given water only. The disease activity index (DAI) of the mice in each group was recorded daily. Seven days later, the mice were sacrificed for histological examination of the intestines using HE staining; the expression of miR-19a mRNA in the intestines was detected using RT-qPCR.

RESULTSCompared with the control group, the model group showed significantly increased DAI and histological scores, and administration of Baitouweng Decoction significantly lowered the DAI and histological scores of the DSS-treated mice. The expression of miR-19a was lowered following DSS treatment, and Baitouweng Decoction treatment caused an increased miR-19a expression in DSS-treated mice.

CONCLUSIONBaitouweng Decoction has therapeutic effects on DSS-induced ulcerative colitis in mice, and this effect is probably mediated by enhancement of miR-19a expression in the intestines.

Animals ; Colitis, Ulcerative ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Intestines ; metabolism ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; metabolism ; Phytotherapy

OBJECTIVETo investigate the efficacy and mechanisms of Bawei Xilei Powder (BXP) in treating ulcerative colitis (UC).

METHODSTotally 103 patients with left hemicolon mild to moderate UC in the active phase at the outpatient clinics of West China Hospital from June 2009 to October 2010 were randomly assigned to the treatment group (55 cases) and the control group (48 cases). Patients in the treatment group were treated with BXP (adding 1 g in 60 mL worm boiled water) and those in the control group received by 50 mg/60 mL hydrocortisone edema solution (once every evening before sleep). The therapeutic course for all was 4 weeks. The disease activity degree (Mayo scoring), endoscopic, and histologic manifestations were compared between post-and pre-treatment in the two groups. The expression of toll-like receptor-4 (TLR4), nuclear factor-kappaB (NF-kappaB), and Occludin were detected.

RESULTSThe clinical remission rate and the response rate in the treatment group were 78.2% and 89.1% respectively, higher than those of the control group (58.3% and 72.9%, P < 0.05).The endoscopically mucosal healing rate was 50.9% in the treatment group and 31.3% in the control group (P < 0.05). The histological remission rate and the effective rate in the treatment group were 32.7% and 65.5% respectively, but higher than those of the control group (27.1% and 58.3%, P > 0.05). The rate of adverse events was 3.8% in the treatment (occurred in 2 cases) and 4.3% in the control group (occurred in 2 cases, P > 0.05). Compared with pre-treatment, the expression of TLR4 and NF-kappaB p65 significantly decreased (P < 0.05), while the expression of Occludin significantly increased (P < 0.05).

CONCLUSIONSBXP was effective and safe in patients with active mild to moderate UC. Its effects might be involved in regulating the expression of inflammatory factors and enhancing mucosa barrier functions. ulcerative colitis; Bawei Xilei Powder; enema therapy

Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Enema ; Humans ; NF-kappa B ; metabolism ; Occludin ; metabolism ; Phytotherapy ; methods ; Toll-Like Receptor 4 ; metabolism

OBJECTIVE: To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity. METHODS: Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed. RESULTS: The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae. CONCLUSION E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.
Animals ; Colitis, Ulcerative/drug therapy* ; Colon/metabolism* ; Interleukin-10 ; Interleukin-12/therapeutic use* ; Male ; RNA, Messenger/metabolism* ; Rats ; Rats, Wistar ; Toll-Like Receptor 2/metabolism*

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan ; Arachidonic Acid/metabolism* ; Mice, Inbred C57BL ; Colon ; Cytokines/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Metabolomics ; Purines/therapeutic use* ; Dextran Sulfate/metabolism* ; Disease Models, Animal ; Colitis/chemically induced*

The cyclooxygenase (COX) is a key enzyme in the coversion of arachidonic acid to prostaglandins. COX-1 is constitutively expressed and is a critical housekeeping gene, whereas COX-2 is rapidly upregulated by growth factors and cytokines and thus responsible for inflammation. COX-2 is frequently overexpressed in colonic adenoma and carcinoma. Specific inhibitors of COX-2 have been shown to induce apoptosis in tumor cells and to inhibit tumor growth in animal models and in humans. Long-standing IBD patients have increased risk of developing colorectal cancer compared to general population. IBD-associated colorectal carcinogenesis is probably promoted by chronic inflammation and closely related to COX-2. In a recent study, powerful chemopreventive ability of selective COX-2 inhibitor was observed in colitis-related colon carcinogenesis in mouse model. But it was reported that even selective COX inhibitors aggravated the DSS-induced colonic inflammation. It is assumed that endogenous PGs are involved in the mucosal defense against DSS-induced colonic ulcerations which are produced by COX-1 at early phase and by COX-2 at late phase. Long-term use of COX-2 inhibitors for the chemoprevention of colitic cancer is needed to define their mechanism of action, that reduce side effects and have specific tumor target.
Animals ; Colitis, Ulcerative/*drug therapy ; Colonic Neoplasms/diagnosis ; Cyclooxygenase 1/metabolism ; Cyclooxygenase 2/metabolism ; Cyclooxygenase 2 Inhibitors/pharmacology/*therapeutic use ; Humans ; Mice ; Models, Animal

The aim of this paper was to investigate the effect of Shaoyao Tang on ulcerative colitis(UC) in rats via regulation of TLR4/NF-κB signal pathway. A total of 56 Wistar rats were randomly divided into 6 groups: normal control group(double distilled water), model group(double distilled water), mesalazine group(10 mL·kg~(-1)), high dose, middle dose and low dose Shaoyao Tang groups(2.4, 1.2, and 0.6 g·mL~(-1)). After UC rat models were established by 2, 4-dinitrochlorobenzene(DNCB)/ethanol enema, the rats received double distilled water or corresponding drugs twice a day for 7 days. After the treatment cycle, the general performance and disease activity index(DAI) of rats were observed on the next day. Then the rats were sacrificed. The length of colon was measured. Macroscopic and histological score of colon were evaluated. Histopathological changes of colon were observed by HE staining. Ultraviolet spectrophotometry detection was used to detect the content of myeloperoxidase(MPO) in blood and colon tissues. The levels of P-selectin, macrophage migration inhibitory factor(MIF) and thromboxane B_2(TXB_2) in blood and colon tissues were determined by ELISA. Immunohistochemistry and Western blot analysis were performed to detect the protein expressions of TLR4 and NF-κB in colon tissues. The results showed that as compared with the model group, Shaoyao Tang of different doses improved the general performance of UC rats. Moreover, high-dose Shaoyao Tang group showed the most obvious effect in scoring of disease activity index(P<0.001); both medium and high doses of Shaoyao Tang significantly inhibited the colon shortening and pathological injury, with significantly decreased expression levels of MPO, P-selectin, MIF and TXB_(2 )in serum and colon tissues of UC rats(P<0.001). Immunohistochemistry and Western blot assay showed that the levels of TLR4 and NF-κB protein expression in the colon tissues of Shaoyao Tang high-dose group were remarkably lower than that in the model group(P<0.001). This study shows that Shaoyao Tang has protective and repairing effects on UC, and its possible mechanism is achieved probably by regulating the TLR4/NF-κB pathway and inhibiting the expressions of MPO, P-selectin, MIF and TXB_2.
Animals ; Colitis, Ulcerative ; drug therapy ; Colon ; Drugs, Chinese Herbal ; pharmacology ; NF-kappa B ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Signal Transduction ; Toll-Like Receptor 4 ; metabolism

The study is aimed to explore the molecular mechanism of the treatment of apocynin in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. 5% DSS was used to mimic the UC model, and 2% apocynin was applied to treat the UC mice. HE staining was used for histopathological evaluation. Chemiluminescence technique was used to measure reactive oxygen species (ROS) production, and the rate of consumption of NADPH inhibited by DPI was detected to determine the NADPH oxidases (NOXs) activity. Western blot was applied to identify the level of p38MAPK phosphorylation, Griess reaction assay to analyze NO production, immunoenzymatic method to determine prostaglandin E2 (PGE2) production, real time RT-PCR and Western blot to identify the expression of iNOS and COX2, and enzyme linked immunosorbent assay to detect inflammatory cytokines TNF-α, IL-6, IFN-γ, IL-1β. Rat neutrophils were separated, and then ROS production, NOXs activity, NO and PGE2 production, NOX1 and p-p38MAPK expression were detected. Compared with the UC group, apocynin decreased ROS over-production and NOXs activity (P < 0.01), reduced p38MAPK phosphorylation, inhibited NO, PGE2 and cytokines production (P < 0.01). Apocynin also decreased NOXs activity and ROS over-production (P < 0.01), inhibited p38MAPK phosphorylation and NOX1 expression, and reduced NO and PGE2 production (P < 0.01) in separated neutrophils from UC mice. Therefore, apocynin could relieve inflammation in DSS-induced UC mice through inhibiting NOXs-ROS-p38MAPK signal pathway, and neutrophils play an important role.
Acetophenones ; pharmacology ; Animals ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Cytokines ; metabolism ; Dextran Sulfate ; Inflammation ; drug therapy ; MAP Kinase Signaling System ; Mice ; NADH, NADPH Oxidoreductases ; metabolism ; Neutrophils ; metabolism ; Rats ; Reactive Oxygen Species ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo observe effects of treatment from the lung and treatment from the intestine on the level of vasoactive intestinal peptide (VIP) in the lung and intestine of ulcerative colitis (UC) rats.

METHODSThe UC rat model was established in 52 rats by using rabbit intestine mucosa tissue allergen combined TNBS-ethanol model (with the model successful rate of 78.0%). Eight rats randomly selected from 40 successfully modeled rats and 8 of 16 rats from the normal group were recruited as the model group and the normal control group before intervention (at week 0). The rest 32 successfully modeled rats were randomly divided into the model group, the Western medicine treatment group (salazosulfapyridine), the treatment from lung group (Huangqi Jiegeng Decoction), and the treatment from intestine group (Huangqi Huanglian Decoction), 8 in each group. Rats in each treatment group were administered with corresponding medication 8 times the dose of a 60 kg adult human. Another 8 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the model group and the normal group by gastrog avage, once per day. Contents of VIP in the lung tissue and the intestinal tissue were detected at week 0 and 4 after 4-week consecutive intervention. Pathomorphological changes of the lung tissue and the colon tissue were observed under light microscope.

RESULTSCompared with the normal control group at week 0, evenly distributed diffuse inflammation could be seen in the pulmonary interstitial tissue; the bronchial wall was thickened; a huge amount of infiltration surrounded bronchi and blood vessels; a large area of necrosis of intestinal mucosa and inflammatory cell infiltration could also be seen in the model group. Pathological injuries of the lung and the colon were more alleviated in each treatment group than in the model group at the same time point. Compared with the normal control group at the same time point, VIP contents in the lung tissue significantly decreased in the model group at the end of week 4 (P<0.05); VIP contents in the colon tissue significantly increased in the model group at the end of week 0 and 4 (P <0.05). Compared with the model group, VIP contents in the lung tissue significantly increased in the Western medicine treatment group and the treatment from lung group at the end of week 4 (P<0.01); VIP contents in the colon tissue significantly decreased in the treatment from lung group and the treatment from intestine group (P<0.05, P<0.01).

CONCLUSIONTreatment from the lung and treatment from the intestine showed predominant advantage in improving local inflammation of the lung and the intestinal tract, alleviating pathological injuries, promoting repair of injuries through regulating VIP contents in the lung tissue and the colon tissue.

Animals ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; Lung ; Male ; Rabbits ; Rats ; Vasoactive Intestinal Peptide

Ulcerative colitis (UC), a chronic inflammatory disease affecting the colon, has a rising incidence worldwide. The known pathogenesis is multifactorial and involves genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Nowadays, the drugs for UC include 5-aminosalicylic acid, steroids, and immunosuppressants. Long-term use of these drugs, however, may cause several side effects, such as hepatic and renal toxicity, drug resistance and allergic reactions. Moreover, the use of traditional Chinese medicine (TCM) in the treatment of UC shows significantly positive effects, low recurrence rate, few side effects and other obvious advantages. This paper summarizes several kinds of active compounds used in the experimental research of anti-UC effects extracted from TCM, mainly including flavonoids, acids, terpenoids, phenols, alkaloids, quinones, and bile acids from some animal medicines. It is found that the anti-UC activities are mainly focused on targeting inflammation or oxidative stress, which is associated with increasing the levels of anti-inflammatory cytokine (IL-4, IL-10, SOD), suppressing the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-23, NF-κB, NO), reducing the activity of MPO, MDA, IFN-γ, and iNOS. This review may offer valuable reference for UC-related studies on the compounds from natural medicines.
Animals ; Colitis, Ulcerative ; drug therapy ; pathology ; Cytokines ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Inflammation ; drug therapy ; metabolism ; Medicine, Chinese Traditional ; Oxidative Stress ; drug effects ; Phytochemicals ; pharmacology