Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway

In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.

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Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽

10.1055/a-1506-3476 ◽

2021 ◽

Author(s):

Jiaqi Wu ◽

Yuzheng Wu ◽

Yue Chen ◽

Mengyang Liu ◽

Haiyang Yu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Activity Index ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Function Evaluation ◽

Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

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Clinical and Structural Effects of Traditional Chinese Medicine and the Herbal Preparation, Iberogast, in a Rat Model of Ulcerative Colitis

Journal of Evidence-Based Complementary & Alternative Medicine ◽

10.1177/2156587213503660 ◽

2013 ◽

Vol 19 (1) ◽

pp. 10-19 ◽

Cited By ~ 9

Author(s):

Suzanne Mashtoub ◽

Bang V. Hoang ◽

Megan Vu ◽

Kerry A. Lymn ◽

Christine Feinle-Bisset ◽

...

Keyword(s):

Ulcerative Colitis ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Disease Activity ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Disease Activity Index ◽

Therapeutic Effects ◽

Inflammatory Disorder

Plant-sourced formulations such as Iberogast and the traditional Chinese medicine formulation, Cmed, purportedly possess anti-inflammatory and radical scavenging properties. We investigated Iberogast and Cmed, independently, for their potential to decrease the severity of the large bowel inflammatory disorder, ulcerative colitis. Sprague Dawley rats (n = 8/group) received daily 1 mL gavages (days 0-13) of water, Iberogast (100 μL/200 μL), or Cmed (10 mg/20 mg). Rats ingested 2% dextran sulfate sodium or water ad libitum for 7 days commencing on day 5. Dextran sulfate sodium administration increased disease activity index scores from days 6 to 12, compared with water controls ( P < .05). On day 10, 200 μL Iberogast decreased disease activity index scores in colitic rats compared with colitic controls ( P < .05). Neither Iberogast nor Cmed achieved statistical significance for daily metabolic parameters or colonic crypt depth. The therapeutic effects of Iberogast and Cmed were minimal in the colitis setting. Further studies of plant extracts are required investigating greater concentrations and alternative delivery systems.

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The effect of selected Lactobacillus strains on dextran sulfate sodium-induced mouse colitis model

Acta Microbiologica et Immunologica Hungarica ◽

10.1556/030.2020.00834 ◽

2020 ◽

Author(s):

Meysam Hasannejad-Bibalan ◽

Ali Mojtahedi ◽

Morteza Eshaghi ◽

Mahdi Rohani ◽

Mohammad Reza Pourshafie ◽

...

Keyword(s):

Histological Analysis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Lactobacillus Rhamnosus ◽

Disease Activity Index ◽

Therapeutic Effects ◽

Probiotic Properties ◽

Markers Of Inflammation ◽

Colitis Model

AbstractInflammatory bowel disease (IBD) comprises two major illnesses: Crohn's disease (CD) and ulcerative colitis (UC). Dextran sulfate sodium (DSS) mouse colitis model has been used in understanding the mechanism of IBD. This study was conducted to examine selected Lactobacillus spp. as potential IBD treatment in the DSS-induced animal model. Balb/c mice were used and colitis was induced by adding 5% dextran sodium sulfate into the drinking water for 8 days. Colon length, disease activity index (DAI) and histological analysis were measured as markers of inflammation in DSS colitis mice. The majority of the Lactobacillus species significantly prevented the shortening of the colon length compared with the DSS group. The DAI scores of mice were significantly reduced following usage of four Lactobacillus strains included: Lactobacillus plantarum 03 and 06, Lactobacillus brevis 02 and Lactobacillus rhamnosus 01. The histological analysis exhibited that oral administration of Lactobacillus strains had therapeutic effects on mice colitis. L. plantarum and L. brevis showed better therapeutic effect against DSS-induced acute colitis mice. The probiotic activities of these three isolates indicated that the probiotic effects were strain specific and none of these useful bacteria could exhibit all of the valued probiotic properties simultaneously.

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Resveratrol Alleviates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Mice by Mediating PI3K/Akt/VEGFA Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.693982 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fang Zhu ◽

Jujia Zheng ◽

Fang Xu ◽

Yiyuan Xi ◽

Jun Chen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Expression Patterns ◽

Intestinal Flora ◽

Inflammatory Factors ◽

Akt Pathway ◽

Sham Operation ◽

Glycerol Phosphate

Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, and its incidence is on the rise worldwide. Resveratrol (RSV), a polyphenolic compound, was recently indicated to exert anti-inflammatory effects on UC. Consequently, the current study was conducted to investigate the mechanism of RSV on alleviating UC in mice by mediating intestinal microflora homeostasis. First, potential targets that RSV may regulate UC were screened using the TCMSP database. Next, mice were treated differently, specifically subjected to sham-operation and dextran sulfate sodium (DSS) induction, and then treated or untreated with RSV. Disease Activity Index (DAI) and Hematoxylin-Eosin (HE) staining were employed to analyze the pathological changes of mice colon. In addition, the expression patterns of inflammatory factors in spleen tissues were detected using ELISA, while the protein expression patterns of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and vascular endothelial growth factor A (VEGFA) in colon tissues were determined by means of immunohistochemistry (IHC) and Western blot analysis. Moreover, changes in intestinal flora and metabolite diversity in UC were analyzed by metabonomics. It was found that RSV played inhibitory roles in the PI3K/Akt pathway in mice. Meanwhile, the administration of RSV induced downregulated the expressions of TNF-α, IFN-γ, IL-1β, IL-6, and IL-4. The six floras of Haemophilus and Veillonella were significantly enriched in UC, while Clostridium, Roseburia, Akkermansia, and Parabacteroides were found to be enriched in control samples. Lastly, it was noted that Akkermansia could regulate the intestinal flora structure of UC mice through triacylglycerol biosynthesis, glycerol phosphate shuttle, cardiolipin biosynthesis, and other metabolic pathways to improve UC in mice. Altogether, our findings indicate that RSV suppressed the activation of the PI3K/Akt pathway and reduced the VEGFA gene expression to alleviate UC in mice.

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EGCG Maintains Th1/Th2 Balance and Mitigates Ulcerative Colitis Induced by Dextran Sulfate Sodium through TLR4/MyD88/NF-κB Signaling Pathway in Rats

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2017/3057268 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Xue Bing ◽

Liu Xuelei ◽

Dong Wanwei ◽

Liang Linlang ◽

Chen Keyan

Keyword(s):

Ulcerative Colitis ◽

Flow Cytometry ◽

Protective Effect ◽

Signaling Pathway ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Mucosal Injury ◽

Inflammatory Factors ◽

Intestinal Mucosal Injury

Objective. To observe the protective effect of epigallocatechin gallate (EGCG) on dextran sulfate sodium- (DSS-) induced ulcerative colitis in rats and to explore the roles of TLR4/MyD88/NF-κB signaling pathway. Methods. Rat models of ulcerative colitis were established by giving DSS. EGCG (50 mg/kg/d) was given to assess disease activity index. HE staining was applied to observe histological changes. ELISA and qPCR detected the expression of inflammatory factors. Flow cytometry was used to measure the percentage of CD4+IFN-γ+ and CD4+IL-4+ in the spleen and colon. TLR4 antagonist E5564 was given in each group. Flow cytometry was utilized to detect CD4+IFN-γ+ and CD4+IL-4+ cells. Immunohistochemistry, qPCR, and western blot assay were applied to measure the expression of TLR4, MyD88, and NF-κB. Results. EGCG improved the intestinal mucosal injury in rats, inhibited production of inflammatory factors, maintained the balance of Th1/Th2, and reduced the expression of TLR4, MyD88, and NF-κB. After TLR4 antagonism, the protective effect of EGCG on intestinal mucosal injury was weakened in rats with ulcerative colitis, and the expressions of inflammatory factors were upregulated. Conclusion. EGCG can inhibit the intestinal inflammatory response by reducing the severity of ulcerative colitis and maintaining the Th1/Th2 balance through the TLR4/MyD88/NF-κB signaling pathway.

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Protective mechanisms of 6-gingerol in dextran sulfate sodium-induced chronic ulcerative colitis in mice

Human & Experimental Toxicology ◽

10.1177/0960327117751235 ◽

2018 ◽

Vol 37 (10) ◽

pp. 1054-1068 ◽

Cited By ~ 11

Author(s):

BO Ajayi ◽

IA Adedara ◽

EO Farombi

Keyword(s):

Ulcerative Colitis ◽

Drinking Water ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Biological Activities ◽

Disease Activity Index ◽

Aberrant Crypt Foci ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive constituent of Zingiber officinale, which has been reported to possess various biological activities. This study was designed to evaluate the role of 6G in chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5% DSS followed by 14 days of normal drinking water. 6G (100 mg/kg) and a reference anti-colitis drug sulfasalazine (SZ) (100 mg/kg) were orally administered daily to the mice throughout exposure to three cycles of 2.5% DSS. Administration of 6G and SZ significantly prevented disease activity index and aberrant crypt foci formation in DSS-treated mice. Furthermore, 6G and SZ suppresses immunoexpression of tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, Regulated on activation, normal T cell expressed and secreted (RANTES), and Monocyte chemoattractant protein-1 (MCP-1) in the DSS-treated mice. 6G effectively protected against colonic oxidative damage by augmenting the antioxidant status with marked decrease in lipid peroxidation levels in DSS-treated mice. Moreover, 6G significantly inhibited nuclear factor kappa B (P65), p38, cyclooxygenase-2, and β-catenin whereas it enhanced IL-10 and adenomatous polyposis coli expression in DSS-treated mice. In conclusion, 6G prevented DSS-induced chronic UC via anti-inflammatory and antioxidative mechanisms and preservation of the Wnt/β-catenin signaling pathway.

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Naringin Exhibited Therapeutic Effects against DSS-Induced Mice Ulcerative Colitis in Intestinal Barrier–Dependent Manner

Molecules ◽

10.3390/molecules26216604 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6604

Author(s):

Ruige Cao ◽

Xing Wu ◽

Hui Guo ◽

Xin Pan ◽

Rong Huang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Therapeutic Potential ◽

Activity Index ◽

Biological Activities ◽

Intestinal Flora ◽

Intestinal Barrier ◽

Disease Activity Index ◽

Dietary Treatment ◽

Therapeutic Effects ◽

Dependent Manner

Naringin is a kind of multi-source food additive which has been explored broadly for its various biological activities and therapeutic potential. In the present study, the protective effect and mechanism of naringin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated. The results showed that naringin significantly alleviated DSS-induced colitis symptoms, including disease activity index (DAI), colon length shortening, and colon pathological damage. The tissue and serum secretion of inflammatory cytokines, as well as the oxidative stress, were decreased accordingly upon naringin intervention. Naringin also decreased the proteins involved in inflammation and increased the expression of tight junction (TJ) proteins. Moreover, naringin increased the relative abundance of Firmicutes/Bacteroides and reduced the content of Proteobacteria to improve the intestinal flora disorder caused by DSS, which promotes the intestinal health of mice. It was concluded that naringin can significantly ameliorate the pathogenic symptoms of UC through inhibiting inflammatory response and regulating intestinal microbiota, which might be a promising natural therapeutic agent for the dietary treatment of UC and the improvement of intestinal symbiosis.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9930187 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Lin Zhou ◽

Fengjuan Yan ◽

Rui Jiang ◽

Jing Liu ◽

Limin Cai ◽

...

Keyword(s):

Ulcerative Colitis ◽

Stem Cells ◽

Hair Follicle ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Inflammatory Factors ◽

Unknown Etiology ◽

Related Factor ◽

Differentiation Potential

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.

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Preventive Effect of Cardiotrophin-1 Administration before DSS-Induced Ulcerative Colitis in Mice

10.20944/preprints201910.0136.v1 ◽

2019 ◽

Author(s):

Ana I Sanchez-Garrido ◽

Vanessa Prieto-Vicente ◽

Victor Blanco-Gozalo ◽

Miguel Arevalo ◽

Yaremi Quiros ◽

...

Keyword(s):

Ulcerative Colitis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Clinical Course ◽

Activity Index ◽

Disease Activity Index ◽

Histological Damage ◽

Current Therapies ◽

Histology And Immunohistochemistry

Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.

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Anti-Inflammatory Effects of Heritiera littoralis Fruits on Dextran Sulfate Sodium- (DSS-) Induced Ulcerative Colitis in Mice by Regulating Gut Microbiota and Suppressing NF-κB Pathway

BioMed Research International ◽

10.1155/2020/8893621 ◽

2020 ◽

Vol 2020 ◽

pp. 1-20

Author(s):

Guosheng Lin ◽

Minyao Li ◽

Nan Xu ◽

Xiaoli Wu ◽

Jingjing Liu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Disease Activity Index ◽

Rrna Gene ◽

Chemical Compositions ◽

Protective Effects ◽

Esi Ms

Aim of the Study. This study is aimed at exploring the effects and pharmacological mechanisms of the extracts from the Heritiera littoralis fruit (EFH) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) in mice. Materials and Methods. The chemical compositions of EFH were identified using LC-ESI-MS. The mice with 3% DSS-induced UC were administered EFH (200, 400, and 800 mg/kg), sulfasalazine (SASP, 200 mg/kg), and azathioprine (AZA, 13 mg/kg) for 10 days via daily gavage. The colonic inflammation was evaluated by the disease activity index (DAI), colonic length, histological scores, and levels of inflammatory mediators. The gut microbiota was characterized by 16S rRNA gene sequencing and analysis. Results. LC-ESI-MS analysis showed that EFH was rich in alkaloids and flavones. The results indicated that EFH significantly improved the DAI score, relieved colon shortening, and repaired pathological colonic variations in colitis. In addition, proteins in the NF-κB pathway were significantly inhibited by EFH. Furthermore, EFH recovered the diversity and balance of the gut microbiota. Conclusions. EFH has protective effects against DSS-induced colitis by keeping the balance of the gut microbiota and suppressing the NF-κB pathway.

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