• The Korean Journal of Food And Nutrition
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• v.35 no.6
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• pp.513-520
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• 2022

The purpose of this study was to investigate the effect of Cheonggukjang pills with aronia and blueberries on dextran sulfate sodium (DSS)-induced colitis in mice. There have been several reports that Cheonggukjang is effective for intestinal health, but the efficacy of Cheonggukjang containing fruits has not yet been reported. In this study, we showed the effect of cheonggukjang pills with blueberries and aronia (CPBA) on DSS-induced colitis in BALB/c mice. CPBA was obtained from Soonchang Moonokae foods and orally administered once a day for 2 weeks before DSS treatment. Colitis was induced in mice by feeding 5% (w/v) DSS drinking water for 7 days. The results showed that CPBA treatment significantly alleviated DSS-induced disease activity index associated with a decrease in colon length. CPBA improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice colon. In addition, CPBA administration significantly reduced the levels of DSS-mediated interferon-γ and interleukin-6 in serum and tumor necrosis factor-α in colon tissue. Moreover, the gene expression of COX-2 and iNOS, which are factors involved in inflammatory signaling, was significantly reduced by CPBA treatment. These results suggest that CPBA have a protective effect against DSS-induced mice colitis and may be a candidate for colitis treatment.

• IMMUNE NETWORK
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• v.22 no.3
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• pp.26.1-26.18
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• 2022

IL-22, a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The tissue-protective properties of IL-22 are expected to be potentially exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and non-functional oligomers. Monomeric IL-22 (mIL-22) was highly purified through a series of 3 separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate STAT3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

• Herbal Formula Science
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• v.31 no.4
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• pp.341-360
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• 2023

Background : To investigate the effect of Hwanggeumjackyak-tang (HJT) on Dextran sulfate sodium (DSS) induced ulcerative colitis. Methods : The experimental animals were divided into three groups; group 1, normal group(Normal); group 2, DSS-induced colitis and untreated group(UT+DSS); group 3, DSS-induced colitis and HJT 200 mg-treated group(HJT200+DSS). We evaluated cytotoxicity after HJT administration and confirmed the anti-inflammatory effect by histological changes in the intestine and genetic analysis of mucosal cells after HJT administration for each group. In addition, microbiological weapons and metabolites in faeces were examined, and the correlation between gut microbiome and metabolites was also investigated. Result : HJT was not observed to be cytotoxic, even at relatively high concentrations, and was effective in protecting the barrier and preventing intestinal inflammation by suppressing the increase in mucus secretion and the expression of inflammatory factors in mucosal cells. HJT treatment affected the increase in the amount and diversity of the gut microbiome in faeces and the increase in metabolites thought to be involved in alleviating inflammation in the gut. Conclusion : This study demonstrates the therapeutic potential of HJT in ulcerative colitis. Further studies should be carried out to confirm our findings.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1506-1512
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• 2023

Quantitative analysis of adenosine triphosphate (ATP) has been widely used as a diagnostic tool in the food and medical industries. Particularly, the pathogenesis of a few diseases including inflammatory bowel disease (IBD) is closely related to high ATP concentrations. A bioluminescent D-luciferin/luciferase system, which includes a luciferase (FLuc) from the firefly Photinus pyralis as a key component, is the most commonly used method for the detection and quantification of ATP. Here, instead of isolating FLuc produced in recombinant Escherichia coli, we aimed to develop a whole-cell biocatalyst system that does not require extraction and purification of FLuc. To this end, the gene coding for FLuc was introduced into the genome of probiotic Saccharomyces boulardii using the CRISPR/Cas9-based genome editing system. The linear relationship (r² = 0.9561) between ATP levels and bioluminescence generated from the engineered S. boulardii expressing FLuc was observed in vitro. To explore the feasibility of using the engineered S. boulardii expressing FLuc as a whole-cell biosensor to detect inflammation biomarker (i.e., ATP) in the gut, a colitis mouse model was established using dextran sodium sulfate as a colitogenic compound. Our findings demonstrated that the whole-cell biosensor can detect elevated ATP levels during gut inflammation in mice. Therefore, the simple and powerful method developed herein could be applied for non-invasive IBD diagnosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.477-484
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• 2014

The purpose of this study was to examine the anti-inflammatory effects of ginger and processed (Beopje) ginger on colitis induced by 2.5% dextran sulfate sodium (DSS) in Balb/c mice. Beopje means a process that herbal medicines are treated by a specific Korean traditional method in order to obtain better pharmacological effects. Mice were fed saline or two different doses of ethanol extracts (ginger and processed (Beopje) ginger) once a day for 14 days. Colitis was induced from day 7 to 14 via administration of 2.5% DSS in drinking water. Experimental animals were divided into four groups: Nor (Normal, 200 ${\mu}L$ of saline without 2.5% DSS-treated group), Con (Control, 200 ${\mu}L$ of saline and 2.5% DSS treated group), G (500 mg/kg of ginger and 2.5% DSS treated group), and BG (500 mg/kg of Beopje ginger and 2.5% DSS treated group). Body weights of both ginger-administered groups increased compared to the control. Colon length increased to 7.6, and 8.0 cm in the G and BG groups, respectively, whereas that of control was 5.7 cm. Histological colon injury induced by DSS-induced colitis was reduced (P<0.05). In serum and DSS-treated colon tissues, mRNA expression levels of IFN-${\gamma}$, IL-6, TNF-${\alpha}$, and IL-12 of the Beopje ginger-treated group were significantly suppressed compared to those of the ginger-treated groups. Expression levels of iNOS and COX-2 of the Beopje ginger-treated group were significantly reduced compared to those of the ginger-treated groups (P<0.05), and BG showed stronger anti-inflammatory effects on colitis. These results indicated that ginger exerted anti-inflammatory effects on DSS-induced colitis in mice, and its effects could be increased through Beopje.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1567-1575
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• 2013

Anti-inflammatory effects of sulfur-fed duck extract on colitis induced by 2.5% dextran sulfate sodium (DSS) were examined in male Balb/c mice. Animals were divided into eight groups: normal (0.1 mL of PBS without 2.5% DSS), control (0.1 mL of PBS with 2.5% DSS), SD-H (3 mL/kg of high sulfur-fed duck extract), SD-L (1 mL/kg of low sulfur-fed duck extract), GD-H (3 mL/kg of high general duck extract), GD-L (1 mL/kg of low general duck extract), GC-H (3 mL/kg of high general chicken extract), and GC-L (1 mL/kg of low general chicken extract). Mice were fed PBS or six different doses of extracts (sulfur-fed duck, general duck, and chicken), once daily for 14 days. Colitis was induced from day 7 to 14 via the administration of 2.5% DSS in drinking water. The colon length was significantly shortened in mice compared to the control group. The administration of SD-H, SD-L, and GD-L increased colon length and decreased histological colon injury from DSS-induced colitis. However, chicken extracts did not recover any clinical sign of the colitis. SD-L significantly suppressed not only the concentrations of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, IL-17A, and IL-12 in serum but also the mRNA expressions of IL-6, TNF-${\alpha}$, iNOS and COX-2 in DSS-treated colon tissues (P<0.05). The administration of SD-H suppressed the concentrations of IL-6 in serum and the mRNA expressions of IL-6, iNOS, and COX-2 in colon tissues. Administration of GD-L suppressed the concentrations of IL-6, TNF-${\alpha}$, and IL-17A in serum and the mRNA expressions of IL-6, iNOS, and COX-2 in colon tissues. The inhibitory effects of sulfur-fed duck extracts were effective at a dose of 1 mL/kg. Our results indicate that sulfur-fed duck extracts may possess anti-inflammatory effects on DSS-induced colitis mice.

• Journal of Nutrition and Health
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• v.37 no.6
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• pp.431-439
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• 2004

Scutellariae Radix (Scu.), one of the immune-regulatory substances, is recognized to play the role in the metabolic process of inflammation, allergy and immunity. It has been traditionally used in the Oriental medicine to treat inflammatory bowel diseases (IBD). The purpose of this study was to evaluate the effects of water extracts of Scutellariae Radix on the spleen lymphocyte immune function in the Balb/c female mice treated with dextran sodium sulfate (DSS) to induce colitis. Water extract of Scutellariae Radix (100 mg/kg) and sulfasalazine (50 mg/kg) were administrated orally for 2 weeks of experimental period. Mice were divided into three experimental groups randomly: DSS group (5％ DSS was ad libitum for 5 days) as control group, DSS ＋ Scu. (water extracts of Scutellariae Radix for 2 weeks after 5％ DSS was ad libitum for 5 days) as experimental group, and DSS ＋ Sulfasalazine group (Sulfasalazine for 2 weeks after 5％ DSS was ad libitum for 5 days) as positive control group. Levels of Ig A, Ig E, CD4$^{＋}$, CD8$^{＋}$, TNF-$\alpha$ and other cytokines were measured. Treatment of DSS for 5 days induced bowel inflammation and the treatment with Scu. water exteract and sulfasalazine significantly recovered the damage. The length of intestine of DSS group was significantly shorter than that of other groups. The serum and fecal concentration of Ig A of SS ＋ Scu group was higher than those of DSS group. The contents of CD4$^{＋}$ T cells was higher in the DSS ＋ Scu. group than the other groups and CD8$^{＋}$ T cells was the lowest in DSS ＋ Sulfasalazine group. The Ig A level of cultured supernatant of spleen lymphocyte was the highest, while the Ig E level was the lowest in SS ＋ Scu group. The concentration of TNF-$\alpha$, cytokine secreted from the Th1 cell in the supernatant spleen lymphocyte, was the highest in the DSS group and the lowest in the DSS ＋ Scu. group. The concentration of IFN-${\gamma}$ and ll...-12 was lower in the DSS ＋ Scu. group than those of the other groups. The concentration of IL-4 in the supernatant of spleen lymphocyte was the lowest in the DSS ＋ Scu. group but IL-10 was not significantly different. Based on these findings, water extract of Scutellariae Radix exhibited the inhibitory effect via IL-4 production thereby inhibited the production of Ig E and strengthened immune system, and alleviated injury in DSS- induced colitis mice model.

• Toxicological Research
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• v.28 no.1
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• pp.39-49
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• 2012

We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of ${\beta}$-catenin was also performed on the mucous membrane of colon. The number of large ACF (${\geq}4$ AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice.

• Journal of Microbiology and Biotechnology
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• v.18 no.12
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• pp.1975-1983
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• 2008

The neuropeptide ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH) has anti-inflammatory property by down regulating the expressions of proinflammatory cytokines. Because ${\alpha}$-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes ${\alpha}$-MSH (L. casei-${\alpha}$-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the ${\alpha}$-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and ${\alpha}$-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-${\alpha}$-MSH on the colitis, L. casei or L. casei-${\alpha}$-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-${\alpha}$-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: $14.45{\pm}0.2\;g$; L. casei-${\alpha}$-MSH: $18.2{\pm}0.12\;g$), colitis score (DSS alone: $3.6{\pm}0.4$; L. casei-${\alpha}$-MSH: $1.4{\pm}0.6$), MPO activity (DSS alone: $42.7{\pm}4.5\;U/g$; L. casei-${\alpha}$-MSH: $10.25{\pm}0.5\;U/g$), survival rate, and histological damage compared with the DSS alone mice. L. casei-${\alpha}$-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and $NF-{\kappa}B$ activation. The ${\alpha}$-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

• Food Science and Preservation
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• v.24 no.8
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• pp.1188-1194
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• 2017

Gochujang, a traditional Korean food, is fermented by mixing red pepper powder, various grain, meju and salt. Changes in the kind of ingredients and fermentation method could increase health functionalities. In this study, in vivo anti-colitis effects of gochujang prepared with mixed grains, bamboo salt baked 3 times and meju starters on DSS-induced colitis in C57BL/6 mice were studied. We prepared gochujang prepared with mixed grains (MG), bamboo salt, and Aspergillus oryzae (A) and Baccillus subtilis (B) mixed starters (MG-AB) and gochujang prepared with MG, bamboo salt and A, B and Lactobacillus plantarum (L) mixed starters (MG-ABL). MG-AB and MG-ABL significantly increased body weight and colon length compared to the control (p<0.05). MG-ABL showed significantly decreased interleukin-6 (IL-6) expression in serum compared to the control and MG-AB group (p<0.05). MG-ABL also regulated mRNA and protein levels of pro-apoptotic Bcl-2-associated X protein (Bax) and anti-apoptotic B-cell lymphoma-2 (Bcl-2) in the mice colon tissue (p<0.05). Therefore, MG-ABL exhibited the increased anticolitis effects by inhibiting damage of colon tissue, probably by regulating a pro-inflammatory cytokine of IL-6 and regulated apoptosis related genes. These results indicated that gochujang changed with good ingredients and starters had colitis preventive effects and might be due to active compounds in mixed grain and bamboo salt, and produced by L during the fermentation of gochujang.