• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.510-519
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• 2022

Tofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.

• Nutrition Research and Practice
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• v.16 no.6
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• pp.700-715
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• 2022

BACKGROUND/OBJECTIVES: Chronic colitis is a risk factor for colorectal cancer (CRC) development in both animals and humans. Previously, we reported that a diet rich in protein (with casein as the protein source) significantly increased the risk of mouse CRC development in a dose-dependent manner. In this study, we investigated the effects of different protein sources on the risk of colitis development. MATERIALS/METHODS: Balb/c mice were divided into 7 experimental groups: 20% casein (20C), 20C-dextran sulfate sodium (DSS), 40% casein-DSS (40CD), 40% whey protein-DSS (40WD), 40% soy protein-DSS (40SD), 40% white meat-DSS (40WMD), and 40% red meat-DSS (40RMD). Mice were fed an experimental diet for 4 wk and received 3% DSS in their drinking water for 6 days during the 4th wk of the experimental period. RESULTS: Compared to other groups, the 40CD group showed the most aggravated colitis with increased disease activity and inflammatory markers. In the 40RMD group, interleukin (IL)-6 levels were the highest among all the groups. The 40SD group showed conflicting effects, for example, elevated mortality and disease activity but decreased nitric oxide (NO) levels. The 40WD group showed attenuated colitis with increased IL-10 levels and decreased NO levels. The 40WMD group showed conflicting effects, including decreased NO levels and elevated fecal lipocalin-2 and IL-6 levels. CONCLUSIONS: These results suggest that, at levels of 40% in the diet, casein and red meat exacerbate colitis, whereas whey protein mitigates it the most effectively.

• Journal of Microbiology and Biotechnology
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• v.33 no.1
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• pp.35-42
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• 2023

This study aimed to identify the therapeutic ability of a novel toll-like receptor (TLR) 5 agonist, KMRC011, on ulcerative colitis induced by Citrobacter rodentium and dextran sulfate sodium in a C57BL/6N mouse model. Ulcerative colitis was induced in the mice by the oral administration of 1% dextran sulfate sodium in sterile drinking water for seven days ad libitum, followed by C. rodentium infection on the seventh day by intra-gastric administration (DSS-CT group). KMRC011 was administered intramuscularly at both 24 h and 15 min before (Treatment 1 group), and at both 15 min and 24 h after (Treatment 2 group) the C. rodentium infection. The length of the large intestine and histopathological counts were significantly greater and mucosal thickness was significantly thinner in the Treatment 1 group compared to the DSS-CT and Treatment 2 groups. Il-6 and Il-10 mRNA expression levels were upregulated, while Ifn-γ and Tnf-α mRNA expression levels were significantly downregulated in the Treatment 1 group, compared to the DSS-CT group. NF-κB p65 expression level was elevated due to ulcerative colitis in the DSS-CT group, but was significantly downregulated in the Treatment 1 group. Overall, KMRC011 showed protective effects against murine colitis by inhibiting NF-κB signaling.

• Journal of Nutrition and Health
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• v.52 no.2
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• pp.139-148
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• 2019

Purpose: Ulcerative colitis is a common inflammatory bowel disease. Prolonged colitis can be a risk factor for the development of colorectal cancer. Mulberry twig (MT, Sangzhi), a dry branch of Morus alba L., which is widely distributed throughout East Asia, has been shown to have anti-inflammatory activities in the cells. However, the effects of MT extracts on colitis in in vivo are limited. Therefore, in this study, we investigated the anti-inflammatory effects of MT extracts in the dextran sulfate sodium (DSS)-induced mouse colitis model. Methods: Six week-old, male ICR mice were divided into 3 groups: Control (n = 5), DSS (n = 7), and DSS+MT (n = 7) groups. Mice in the DSS and DSS+MT groups were administrated 3% DSS in drinking water for 5 days to induce colitis. At the same time, water extracts of MT (5 g/kg body weight/day) were orally administered to mice in the DSS+MT groups for 5 days. Results: The MT extracts significantly reduced the clinical and pathological characteristics of colitis. Disease activity index, mucosal thickness, and colonocyte proliferation were significantly reduced in the DSS+MT group compared with the DSS group. Furthermore, MT administration reduced the levels of plasma $TNF-{\alpha}$, IL-6, and the colonic myeloperoxidase activity as well as mRNA expression of $TNF-{\alpha}$, IL-6, Cox-2, and iNOS. Conclusion: Taken together, these results suggest that MT water extracts have potent anti-colitis activities in the mouse colitis model.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.9-14
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• 2022

Ulcerative colitis is a disease that causes inflammation in the mucosal or submucosal layer of the colon. Previous studies have reported that obesity increases the prevalence of ulcerative colitis and aggravates the progression. This study was therefore undertaken to investigate whether curcumin inhibits the progression of ulcerative colitis caused by obesity. Mice were bred on a high-fat diet to induce obesity, and curcumin was administered with the high-fat diet to confirm the anti-inflammatory effect. To induce ulcerative colitis, dextran sulfate sodium (DSS) was administered orally, and clinical symptoms of colitis were subsequently observed. For histological evaluation of curcumin, the colon, liver and abdominal fat tissue samples were prepared and analyzed by hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (PAS) staining. Our results confirm that consumption of curcumin resulted in decreasing the score of the disease activity index, and inhibited shortening of the colon length. In addition, inflammatory cell infiltration and mucosal damage were inhibited in the colon tissue of ulcerative colitis exacerbated by obesity. We further confirmed that exposure to curcumin significantly reduced the steatosis area of the liver and adipocytes of abdominal fat. In conclusion, we believe that curcumin can be applied as a therapeutic agent to treat ulcerative colitis, by inhibiting the progression of colitis caused by obesity.

• The Korea Journal of Herbology
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• v.39 no.1
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• pp.31-38
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• 2024

Objectives : Ulcerative colitis is a chronic recurrent inflammatory disease of the gastrointestinal tract. However, there are some drawbacks to long-term drug therapy such as the risk of opportunistic infections. Recently, there was an increasing interest on the use of khorasan Kamut wheat because of their higher value of selenium and fiber than modern wheat. The present study was aimed to investigate the effect of Kamut brand wheat enzyme (Kamut WE) diet on colon health in dextran sulfate sodium (DSS)-induced colitis mice. Methods : Female C57BL/6J mice were divided into 6 groups. (1) normal (Water and AIN-93G diet), (2) control (1.25% DSS and AIN-93G diet), (3) Kamut WE (1.25% DSS and Kamut WE diet), (4) normal (Water and AIN-93G diet), (5) control (2.50% DSS and AIN-93G diet), (6) Kamut WE (2.50% DSS and Kamut WE diet). Dietary intake, body weight change, disease activity index (DAI), colon length and spleen weight were monitored. Results : Kamut WE group alleviated colitis symptom, including dietary intake loss, DAI (weight loss, loose stools, bleeding), colon length shortening and spleen swelling. Further, Kamut WE diets showed a significant effect against pathological damage by the increased colon length, decreased DAI and spleen weight in DSS 1.25% as well as DSS 2.50%. Conclusions : Our study provides evidence that Kamut WE diet increased colon length, decreased DAI and spleen weight in intestinal inflammation.

• The Korean Journal of Food And Nutrition
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• v.37 no.1
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• pp.1-8
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• 2024

This study investigated the effect of Lactiplantibacillus plantarum JSA22-fermented rice drinks on dextran sodium sulfate (DSS)-induced colitis in mice. Twenty-four mice were randomly assigned; No colitis (Con), colitis with tap water (DSS-only), colitis with unfermented rice (DSS-UFR), and colitis with fermented rice (DSS-FR). After inducing colitis with 2% DSS for 5 days, they were given Tap water, UFR drink, or FR drink for an additional 6 days. The DSS-FR group had significantly lower Disease Activity Index (DAI) scores compared to the DSS-only group, but no significant difference with the DSS-UFR group. Colon length was reduced in the DSS-only group. The DSS-only group had significantly higher IL-6 mRNA levels compared to the Con group, while the DSS-FR groups showed significantly lower IL-6 mRNA levels compared to the DSS-only group. These results suggest that rice drinks fermented with Lactiplantibacillus Plantarum JSA22 ameliorate the severity of DSS-colitis, by potentially reducing proinflammatory cytokines.

• 한국약용작물학회:학술대회논문집
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• 2010.10a
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• pp.343-344
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• 2010

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.93.2-93.2
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• 2000

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.211-211
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• 2020