Baitouweng Decoction Alleviates Dextran Sulfate Sodium–Induced Ulcerative Colitis Through Nrf2/HO-1 Pathway Activation and HMGB1 Downregulation

2021 ◽  
Author(s):  
Weina Zhu ◽  
Chunhua Ma ◽  
Fuqiong Zhou ◽  
Jie Ruan ◽  
Yajie Zhang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathways ◽  
Adhesion Molecule ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Aminosalicylic Acid

Abstract BackgroundThe phrase “baitouweng (BTW) decoction” was first recorded in the ancient Chinese medical text Shang Han Za Bing Lun. BTW decoction has been widely used by practitioners of (traditional) Chinese medicine.[VN1] It has been used to treat ulcerative colitis (UC) for hundreds of years. In this study, we investigated the antioxidative properties of BTW and the intestinal immunity of mice with dextran sulfate sodium (DSS)–induced UC and further investigated the mechanism by which BTW alleviates UC.MethodsUC was induced in mice by using DSS. The mice were randomly divided into the following five groups: control, DSS, BTW (5, 10, and 20 g/kg[VN2] ), berberine (BBR), and 5-aminosalicylic acid (5-ASA). Except for the control group, 3% DSS was administered in drinking water to all groups for 7 days, and and the other groups were intragastrically administered with BTW（5, 10, and 20 g/kg）、BBR and 5-ASA independently.[VN3] After gavaging for 12 days, the mice were killed. Subsequently, body weight loss, colon length, colon histopathology, inflammatory cytokine expression, and intestinal protein expression were measured.ResultsBTW effectively reduced the symptoms and histopathological scores of UC mice. Additionally, it downregulated the inflammatory factors interleukin (IL)-6 and IL-1β, the immunoglobulins vascular cell adhesion molecule 1 and intercellular adhesion molecule 1, and metalloprotease matrix metallopeptidase 9. Moreover, it downregulated high mobility group box 1 protein. Furthermore, it inhibited the nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.ConclusionBTW considerably alleviated the inflammatory symptoms of mice with acute colitis, and the latent mechanism of BTW may be related to various signaling pathways, including the modulation of antioxidant signaling pathways such as the Nrf2/HO-1 pathway.

scholarly journals Regulatory effect of Garidisan on dysbiosis of the gut microbiota in the mouse model of ulcerative colitis induced by dextran sulfate sodium

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling-yan Pei ◽  
Yu-shi Ke ◽  
Huan-hu Zhao ◽  
Wei-zhi Liu ◽  
Lin Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Therapeutic Effect ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Control Group ◽  
Group Model ◽  
Regulatory Effect ◽  
Model Group

Abstract Background Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. Methods The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. Results The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. Conclusion Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.

scholarly journals Changes in the Pharmacokinetics of Phenytoin in Dextran Sulfate Sodium–Induced Ulcerative Colitis in Mice

2017 ◽  
Vol 36 (6) ◽  
pp. 485-491 ◽  
Author(s):  
Yoshiki Kusunoki ◽  
Yurika Kido ◽  
Yuichi Naito ◽  
Risako Kon ◽  
Nanaho Mizukami ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Protein Expression ◽  
Messenger Rna ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Plasma Concentrations ◽  
Control Group ◽  
Time Curve ◽  
Blood Concentrations ◽  
Expression Levels

We previously demonstrated that the expression levels of drug-metabolizing enzymes, cytochrome P450 (CYP) enzymes, in the liver are significantly decreased in a murine model of ulcerative colitis (UC). In this study, we investigated changes in the pharmacokinetics of phenytoin, a CYP2C substrate drug, in the presence of UC. Colitis was induced by feeding male mice 3.5% dextran sulfate sodium (DSS) dissolved in drinking water for 10 days. The messenger RNA (mRNA) expression of CYP2C29 and CYP2C37 and the protein expression of CYP2C in the liver were evaluated via real-time reverse transcription–polymerase chain reaction and Western blotting, respectively. In DSS-treated animals, both mRNA and protein expression levels of CYP2C in the liver were significantly reduced relative to those in control animals (by 20%-40%). Phenytoin (30 mg/kg) was administered orally in a single dose to mice, and plasma concentrations were measured. Plasma concentrations of phenytoin were higher in the DSS-treated group than in the control group at 12, 24, and 36 hours after administration. Animals given DSS also exhibited a higher area under the plasma concentration–time curve extrapolated to infinity (AUCinf, 315 μg·h/mL), a delayed elimination half-life ( T1/2, 8.1 hours), and a decreased body clearance (CL/F, 3.52 mL/h) compared with that of control animals (AUCinf, 215 μg·h/mL; T1/2, 3.6 h; CL/F, 5.58 mL/h). This study indicated that the presence of UC decreases CYP2C expression levels in the liver, thereby delaying the metabolism of CYP2C substrates, including phenytoin, and increasing blood concentrations of these substrates.

scholarly journals PROTECTIVE EFFECT OF HYDRO-ALCOHOLIC EXTRACT OF DRIED FRUITS OF HELICTERES ISORA IN DEXTRAN SULFATE SODIUM (DSS) INDUCED ULCERATIVE COLITIS IN EXPERIMENTAL WISTAR RATS

2020 ◽  
pp. 325-330
Author(s):  
Prajakta Murudkar ◽  
Swati Kolhe ◽  
Sachin Tembhurne
Keyword(s):  
Ulcerative Colitis ◽  
Drinking Water ◽  
Wistar Rats ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Control Group ◽  
Alcoholic Extract ◽  
Standard Drug ◽  
Dried Fruits ◽  
Helicteres Isora

Ulcerative colitis is a most common form of inflammatory bowel disease (IBD) which mainly affect colon. The treatment of ulcerative colitis depends upon severity of the diseases. The aim of the present study was to determine the effect of hydroalcoholic extract of dried fruits of Helicteres isora in dextran sulfate sodium induced ulcerative colitis in experimental wistar rats. In this study wistar rats of either sex were divided into five experimental groups, where control group recived only distilled water. Group 2 was negative control group which received 4% dextran sulfate sodium (DSS) from drinking water between 15th to 21st day. Group 3 received low dose of hydroalcholic extract of Helicteres isora (HI) at a dose 100mg/kg orally along with 4% DSS from drinking water between from drinking water between 15th to 21st day. Group 4 received high dose of hydroalcholic extract of Helicteres isora (HI) at a dose 200mg/kg orally along with 4% DSS from drinking water between from drinking water between 15th to 21st day. In group 5 sulfasalazine was used as a standard drug at a dose 100mg/kg orally along with 4% DSS from drinking water between from drinking water between 15th to 21st day. Twenty four hours after treatment animals were sacrificed and further macroscopical, biochemical, histopathological evaluation was done and all the results were compare with control at p<0.05 significant value.

scholarly journals Akkermansia muciniphila Exerts Strain-Specific Effects on DSS-Induced Ulcerative Colitis in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Qing Liu ◽  
Wenwei Lu ◽  
Fengwei Tian ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Immune Defense ◽  
Rapid Screening ◽  
Comparative Genomic ◽  
Control Group ◽  
Akkermansia Muciniphila ◽  
Positive Effects

Akkermansia muciniphila is a commensal bacterium of the gut mucus layer. Although both in vitro and in vivo data have shown that A. muciniphila strains exhibit strain-specific modulation of gut functions, its ability to moderate immunity to ulcerative colitis have not been verified. We selected three isolated human A. muciniphila strains (FSDLZ39M14, FSDLZ36M5 and FSDLZ20M4) and the A. muciniphila type strain ATCC BAA-835 to examine the effects of different A. muciniphila strains on dextran sulfate sodium-induced colitis. All of the A. muciniphila strains were cultured anaerobically in brain heart infusion medium supplemented with 0.25% type II mucin from porcine stomach. To create animal models, colitis was established in C57BL/6 mice which randomly divided into six groups with 10 mice in each group by adding 3% dextran sulfate sodium to drinking water for 7 days. A. muciniphila strains were orally administered to the mice at a dose of 1 × 109 CFU. Only A. muciniphila FSDLZ36M5 exerted significant protection against ulcerative colitis (UC) by increasing the colon length, restoring body weight, decreasing gut permeability and promoting anti-inflammatory cytokine expression. However, the other strains (FSDLZ39M14, ATCC BAA-835 and FSDLZ20M4) failed to provide these effects. Notably, A. muciniphila FSDLZ20M4 showed a tendency to exacerbate inflammation according to several indicators. Gut microbiota sequencing showed that A. muciniphila FSDLZ36M5 supplementation recovered the gut microbiota of mice to a similar state to that of the control group. A comparative genomic analysis demonstrated that the positive effects of A. muciniphila FSDLZ36M5 compared with the FSDLZ20M4 strain may be associated with specific functional genes that are involved in immune defense mechanisms and protein synthesis. Our results verify the efficacy of A. muciniphila in improving UC and provide gene targets for the efficient and rapid screening of A. muciniphila strains with UC-alleviating effects.

scholarly journals Protective Effect of Spirulina platensis Extract against Dextran-Sulfate-Sodium-Induced Ulcerative Colitis in Rats

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2309 ◽  
Author(s):  
Mohamed A. Morsy ◽  
Sumeet Gupta ◽  
Anroop B. Nair ◽  
Katharigatta N. Venugopala ◽  
Khaled Greish ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Drinking Water ◽  
Spirulina Platensis ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Control Group ◽  
Protective Effects ◽  
Hydroalcoholic Extract ◽  
Tnf Α

Inflammatory bowel disease is a multifactorial inflammatory condition. This study aimed to test the protective effects of Spirulina platensis against ulcerative colitis (UC). UC was induced in thirty-six male Wistar rats by adding dextran sulfate sodium (DSS) to their drinking water, while a control group received only drinking water. UC rats were equally-divided into six groups that received a single oral daily dose of vehicle (DSS), sulfasalazine (SSZ, 50 mg/kg/day), chloroform or the hydroalcoholic extracts of Spirulina platensis (100 or 200 mg/kg/day) for 15 days, and then blood and colon samples were harvested for determination of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), myeloperoxidase (MPO), and histopathology. At the end of the study, compared to time-matched controls, UC rats showed increased TNF-α (1.64-fold), IL-6 (5.73-fold), ESR (3.18-fold), and MPO (1.61-fold), along with loss of body weight (24.73%) and disease activity index (1.767 ± 0.216 vs. 0 ± 0), p < 0.001. These effects were prevented by SSZ treatment (p < 0.001 vs. DSS). The hydroalcoholic extract of Spirulina platensis dose-dependently modulated all DSS-induced inflammatory changes. However, the chloroform extract significantly lowered only IL-6 and ESR, but not TNF-α or MPO levels. The protective effects of the hydroalcoholic extract of Spirulina platensis against experimental UC involved mitigation of DSS-induced inflammation.

scholarly journals Protective Effect of Lycium barbarum Polysaccharides and Capsaicin in Rats With Dextran Sulfate Sodium-Induced Ulcerative Colitis via Anti-inflammation and Antioxidation

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 306-306
Author(s):  
Yu-Shan Chen ◽  
Yu Zhi Lian ◽  
Jane Chao
Keyword(s):  
Ulcerative Colitis ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Elevated Serum ◽  
Control Group ◽  
Lycium Barbarum ◽  
Tnf Α ◽  
Anti Inflammation ◽  
Lycium Barbarum Polysaccharides

Abstract Objectives Ulcerative colitis (UC) is a chronic inflammatory disease in the colon, and the prevalence of UC is increasing worldwide. Lycium barbarum polysaccharides (LBP) from wolfberry extract has immunomodulatory effects, and act as a prebiotics candidate. Capsaicin (CAP) as an active ingredient of chili peppers has the potential for anti-inflammation and antioxidation. This study investigated the effects of LBP and CAP on anti-inflammation and antioxidation in rats with dextran sulfate sodium (DSS)-induced UC. Methods Male Sprague-Dawley rats were divided into five groups: control, UC (DSS), UC treated with 100 mg/kg bw LBP (LBP), UC treated with 12 mg/kg bw CAP (CAP), and UC treated with a combination of 50 mg/kg bw LBP and 6 mg/kg bw CAP (MIX) groups. The treatment of LBP and/or CAP was daily given by oral gavage from week 1 to week 4, and UC was induced by 5% DSS in drinking water for 6 days during week 3. Results The DSS group significantly increased disease activity index (DAI) scores, the levels of pro-inflammatory cytokines interleukin-6 (IL-6) in the serum and tumor necrosis factor-α (TNF-α) in the colon, and serum lipid peroxidation malondialdehyde (MDA) levels compared with the control group. While the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in the serum were significantly decreased in the DSS group. The LBP, CAP, and MIX groups significantly decreased DAI scores on day 6 during the DSS-induced period. Compared with the DSS group, the LBP group significantly decreased serum IL-6 and serum MDA levels, but increased serum CAT activity. The CAP group significantly decreased serum IL-6 levels. The MIX group significantly reduced serum IL-6 and colon TNF-α levels, but elevated serum SOD activity. Conclusions The results suggest that administration of LBP and/or CAP attenuate DSS-induced UC symptoms in rats through the anti-inflammatory and antioxidant activities. Funding Sources This study was supported by the Ministry of Science and Technology, Taiwan (grant no. MOST 108–2320-B-038–052-MY3).

scholarly journals Saccharomyces boulardii Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Regulating NF-κB and Nrf2 Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hui Gao ◽  
Yinzheng Li ◽  
Jie Sun ◽  
Huzi Xu ◽  
Meng Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Nuclear Translocation ◽  
Intestinal Barrier ◽  
Saccharomyces Boulardii ◽  
Heme Oxygenase 1 ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Immunomodulatory Effects

Saccharomyces boulardii (S. boulardii) is a probiotic yeast that is widely used to treat gastrointestinal disorders. The present study is aimed to explore the therapeutic effects of S. boulardii on dextran sulfate sodium- (DSS-) induced murine ulcerative colitis (UC) and illustrate the mechanisms of action. C57BL/6 mice were administered S. boulardii (105 and 107 CFU/ml, p.o.) for 3 weeks and then given DSS [2.5% ( w / v )] for one week. Administration of S. boulardii prevented DSS-induced reduction in body weight, diarrhea, bloody feces, decreased colon length, and loss of histological structure. Moreover, S. boulardii protected the intestinal barrier by increasing the levels of tight junction proteins zona occludens-1 and Occludin and exerted immunomodulatory effects in DSS-induced mice. Furthermore, S. boulardii suppressed the colonic inflammation by reducing the levels of Interleukin-1β, Interleukin-6, and Tumor necrosis factor alpha and restored myeloperoxidase activity in mice exposed to DSS. S. boulardii also mitigated colonic oxidative damage by increasing the levels of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase 1) and glutathione and decreasing malondialdehyde accumulation. Further studies identified that S. boulardii suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit by decreasing IκKα/β levels, while promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in DSS-exposed mice. Collectively, S. boulardii possessed an appreciable therapeutic effect against the experimental mice model of UC. The protective mechanism of S. boulardii may involve inhibition of NF-κB-mediated proinflammatory signaling and activation of Nrf2-modulated antioxidant defense in addition to intestinal barrier protective and immunomodulatory effects.

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