• The Journal of Korean Medicine
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• v.37 no.3
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• pp.13-26
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• 2016

Objectives: Inflammatory bowel disease (IBD) is chronic inflammatory disorders of the intestines. Due to limitation of conventional treatment including steroids, herbal medicines have emerged as possible therapeutic options for IBD. The purpose of the current study was to investigate the therapeutic and prophylactic effects and mechanisms of Zostera Marina water extract (ZME) on DSS-induced colitis. Methods: Colitis was induced by DSS in Balb/c mice. In pre-treatment setting, ZME was administered 7 days before DSS treatment and in co-treatment setting, ZME was simultaneously administrated with DSS treatment. In both settings, ZME 100, 300 and 1000 mg/kg were orally administered twice a day, respectively. Mice weight and clinical findings were measured daily. Colon length, macroscopic findings and histological damages of colon mucosa were assessed at the end of experiments. The levels of cytokines including TNF-${\alpha}$, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, IL-10 and IL-17 were measured by Biometric Multiplex Cytokine Profiling method. Results: In a dose dependent manner, ZME significantly inhibited the colon shortening, and improved macroscopic score and histological score. However, there were insignificant changes on inhibition of weight loss and improvement of clinical score. There were no significant differences of effects between co-treatment and pre-treatment settings. ZME 300 and 1000 mg/kg groups significantly inhibited IFN-${\gamma}$. Only ZME 1000 mg/kg group significantly inhibited TNF-${\alpha}$, IL-$1{\beta}$ and IL-6. Conclusions: The current results show the possibility of therapeutic use and its prophylactic application of ZME on inflammatory bowel diseases. Future studies for targeted mechanisms of ZME are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2235-2245
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• 2016

Ulcerative colitis (UC) results from colonic epithelial barrier defects and impaired mucosal immune responses. In this study, we aimed to investigate the modifying effects of a Spirogyra neglecta extract (SNE), a polysaccharide extract (PE) and a chloroform fraction (CF) on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the mechanisms. To induce colitis, ICR mice received 3% DSS in their drinking water for 7 days. Seven days preceding the DSS treatment, oral administration of SNE, PE and CF at doses of 50, 25 and 0.25 mg/kg body weight (low dose), 200, 100 and 1 mg/kg body weight (high dose) and vehicle was started and continued for 14 days. Histologic findings showed that DSS-induced damage of colonic epithelial structure and inflammation was attenuated in mice pre-treated with SNE, PE and CF. Furthermore, SNE and PE significantly protected colonic epithelial cells from DSS-induced cell cycle arrest, while SNE, PE and CF significantly diminished apoptosis. Proteome analysis demonstrated that SNE and PE might ameliorate DSS-induced colitis by inducing antioxidant enzymes, restoring impaired mitochondria function, and regulating inflammatory cytokines, proliferation and apoptosis. These results suggest that SNE and PE could prevent DSS-induced colitis in ICR mice by protection against and/or aiding recovery from damage to the colonic epithelium, reducing ROS and maintaining normal mitochondrial function and apoptosis.

• The Korea Journal of Herbology
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• v.30 no.3
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• pp.35-40
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• 2015

Objectives : Zizyphus jujube (ZJ) has been used as a traditional medicine for various diseases. However, the inhibitory effect of ZJ on intestinal inflammation has not been fully understood, yet. The aim of this study is to investigate anti-colitis activity of ZJ in dextran sulfate sodium (DSS)-induced colitis mouse model. Methods : To investigate the protective effects of ZJ,the colitis mice were induced by drinking water containing 5% DSS for 7 days. Mice were randomized into groups receiving ZJ (500 mg/kg), sulfasalazine (SFZ) (150 mg/kg) as a positive control, or water as a negative control. We assayed the effects of ZJ on DSS-induced the clinical signs, measuring weight loss, colon length and disease activity index (DAI). Additionally, to find a possible explanation for the anti-inflammatory effects of ZJ, we evaluated the effects of ZJ on the production of prostaglandin $E_2$ ($PGE_2$) and expression of cyclooxygenase (COX)-2 in colitis tissue. Results : The results showed that mice treated with DSS showed considerable clinical signs, including weight loss, and reduced colon length. However, administration of ZJ significantly reduced the weight loss, shortens colon length, and improved DAI as clinical symptoms. Moreover, ZJ inhibited the $PGE_2$ production and COX-2 expression levels in DSS-treated colon tissues. Conclusions : Collectively, the findings of this study provide us with novel insights into the pharmacological actions of ZJ as a potential molecule for use in the treatment of intestinal inflammation including ulcerative colitis.

• Korean Journal of Medicinal Crop Science
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• v.19 no.1
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• pp.16-23
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• 2011

This study was conducted to investigate the anti-inflammatory effects of Pruns mume, Schisandra chinensis, Chaenomeles sinensis-- Prunus mume mixtrue (PM) treatment on colitis induced in mice by dextran sodium sulfate (DSS) treatment. A total of 25 male BALB/c mice (average weight $20.7\;{\pm}\; 1.6 \;g$) were divided into 5 treatment groups and fed a commercial diet (A), PM administration (B), commercial diet + induced colitis by DSS (C), PM administration + induced colitis by DSS (D) and sulfasalazine + induced colitis by DSS (E). We found that PM treatment (D) and sulfasalazine (E) decreased the expression of $TNF-{\alpha}$ and COX-2 compared to the DSS-induced colitis group (C). The expression of IL-4, STAT6, $IFN-{\gamma}$, STAT1 was decreased in group D and group E compared to the colitis group (C), COX-2 and STAT1 were more decreased in group D. The serum IgE levels decreased in the PM treatment groups (C and D) compared to the non-PM treatment groups (A and B) although there was no significant difference between the PM treatment groups. It is notable that a therapeutic application of the PM extracts ameliorated DSS-induced colitis in mice.

• Herbal Formula Science
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• v.16 no.2
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• pp.171-182
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• 2008

The aqueous extract of Schisandra chinensis, Evodia rutaecarpa and meal (SEM-Ex) has been traditionally used in the Oriental countries as an astringent. However, little is known about the effects of aqueous extract of SEM-Ex on dextran-sulfate sodium (DSS)-induced colitis in mice. In this study, we investigated the protective effects of SEM-Ex on DSS-induced colitis in mice. An experimental colitis was induced by daily treatment with 5% DSS. SEM-Ex was orally administered from day 2 of DSS treatment in the different dose (10-50 mg/kg body weight). SEM-Ex reduced significantly clinical sign of DSS-induced colitis, including body weight loss, shorten colon length, increased disease activity index (DAI), and histological colon injury. Moreover, SEM-Ex suppressed significantly not only the serum haptoglobin levels and the activities of myeloperoxidase (MPO), but also the colon tissue expression levels of monocyte chemoattractant protein-1 (MCP-1) in DSS-induced mice. In contrast, SEM-Ex increased significantly the colon tissue expression levels of granular colony stimulating factor (G-CSF) well known as anti-inflammatory cytokine. These results suggest that SEM-Ex administration could reduce significantly the clinical signs and regulate of chemokine and anti-inflammatory cytokine in DSS-induced model mice. Therefore, these properties may contribute to the strong anti-ulcerative colitis (UC) response effect of SEM-Ex.

• Korean Journal of Pharmacognosy
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• v.39 no.2
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• pp.104-109
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• 2008

We previously reported that anti-inflammatory properties of poncirin, isolated from fruit of Poncirus trifoliata, might be the result from the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis $factor-{\acute{a}}$ ($TNF-{\alpha}$) and interlukin-6 (IL-6) expression via the down-regulation of $NF{-\kappa}B$ binding activity. In this study, we investigated whether poncirin has an inhibitory effect on the production of pro-inflammatory mediators ex vivo and whether poncirin could relieve the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice model of inflammatory bowel disease. Poncirin significantly inhibited the productions of NO, IL-6 and $TNF-{\alpha}$ in lipopolysaccharide (LPS)-induced mouse peritoneal macrophage. In addition, poncirin-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of poncirin-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). In addition, suppression of plasma NO and IL-6 productions of poncirin-treated mice was also observed in DSS-induced colitis. These results suggest that poncirin has potentially useful anti-inflammatory effects mediated by suppression of inflammatory mediator productions.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.14-21
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• 2015

Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.

• The Korean Journal of Food And Nutrition
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• v.34 no.2
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• pp.146-155
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• 2021

This study observed the anti-inflammatory effect of the polysaccharide derived from the mycelium of Tremella fuciformis in mice with colitis induced with dextran sulfate sodium (DSS). The experimental groups were normal, DSS, DSS-TFL50, DSS-TFH100, and suflasalazine. Body weights, colon lengths, and organ weights were measured, and the plasma level of pro-inflammatory cytokine and mRNA and protein expression in colon tissue were analyzed. Body weight loss, a symptom of DSS-induced colitis, was suppressed by DSS-TF and the speed of weight recovery proceeded rapidly. In addition, DSS-TF showed a significant inhibitory effect on the decrease of colon length typically caused by colon damage. TNF-α, IL-6 and IL-1β cytokine levels in plasma were reduced in DSS-TF and positive control groups. TNF-α, COX-2 and IL-1β mRNA expression in colon tissue were inhibited in DSS-TF and positive control, and it was significantly different from that of the DSS group. The protein expression of inflammation-related genes (IL-6, TNF-α and COX-2) in the colon tissue was significantly increased by DSS compared to that of the normal group, but by DSS-TFL50, DSS-TFH100 and sulfasalarin decreased. In conclusion, the polysaccharide derived from the mycelium of Tremella fuciformis showed the anti-inflammatory effect on DSS-induced colitis in mice.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.422-433
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• 2018

Objective: Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied. Methods: Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclooxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Results: Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. Conclusion: IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.

• Parasites, Hosts and Diseases
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• v.60 no.5
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• pp.309-315
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• 2022

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.