• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.6
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• pp.439-446
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• 2016

The purpose of this study was to examine the effects of Angelica gigas Nakai on ulcerative colitis. Mice were divided into 5 groups: Control group, DSS group, 5-ASA group, 50mg/kg Angelica gigas Nakai group, 100mg/kg Angelica gigas Nakai group. Four groups, excluding the control group, were fed a 5% solution of dextran sulfate sodium(DSS) in water for 7days to induce ulcerative colitis. Each water extract was administrated orally for 7 days in 5-ASA group, 50mg/kg Angelica gigas Nakai group and 100mg/kg Angelica gigas Nakai group. 5 groups were evaluated by weight, length of intestine, weight of spleen, disease activity index(DAI), amount of cytokine IL-6 production, thickness of bowel wall and degree of inflammatory cell infiltration and intestinal tissue damage. Comparing to DSS group, 100 mg/kg Angelica gigas Nakai group showed significant suppressive effect of weight loss until 4th day of experiment while 50 mg/kg Angelica gigas Nakai group showed no significant effect of suppression. Decrease of intestinal length, enlargement of spleen, intestinal tissue damage and thickening of bowel wall were significantly suppressed in both 50 mg/kg and 100mg/kg Angelica gigas Nakai group. Also disease activity and cytokine IL-6 production were inhibited significantly. Based on this result, Angelica gigas Nakai seemed to have anti-inflammatory effect and also seemed to suppress histological changes and aggravation of ulcerative colitis.

• Journal of Nutrition and Health
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• v.41 no.5
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• pp.391-401
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• 2008

Probiotics have emerged as a potential treatment modality for numerous gastrointestinal disorders, including IBD. However, few probiotics have undergone appropriate preclinical screening in vivo. Kefir is considered a probiotic, benefiting the host through its effects in the intestinal tract. Despite numerous studies examining the action of probiotics on the host organism, few have analyzed the effects on intestinal environment. We assessed the protective effect of kefir for three weeks before inducing colitis with 2% dextran sodium sulfate for five days. The DSS loads were similar in all DSS treatment group. The results of the experiment are as follows. Food intake and FER of experimental groups were not significantly different each other, but water consumption tended to be higher in all DSS treatment groups as compared with the normal control. And visual inspection of feces revealed mild diarrhea in rat given 2% DSS. The anti-inflammatory activity of kefir was determined by myeloperoxidase activity during the DSS treatment, and there was no significant difference in any group. The levels of thiobarbituric acid reactive substances (TBARS) as a colonic lipid peroxidation were significantly lower in the kefir intake groups than in rats treated with 2% DSS alone. The DNA % in tail and tail moment values as a DNA damage level of the blood lymphocytes in kefir intake groups tended to be lower than 2% DSS treatment alone, especially tail lengths were significantly diminished. According to the colonic histopathological assay, there were a severe inflammation of lamina propria and submucosa and mild edema in mucosa and sub mucosa in DSS alone treated group. We found a slight regenerative change in kefir treatment groups. In our experiments, this means that ulcerative colitis related to oxidative injury might be prevented by kefir as a probiotic. Further studies of the potential benefits of kefir as a probiotic in inflammatory condition are encouraged.

• Journal of Food Hygiene and Safety
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• v.25 no.3
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• pp.269-277
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• 2010

Selenium is an essential micronutrient for normal body function and functions as an essential constituent of selenoproteins. This study was carried out to investigate effect of selenium on the formation of colonic aberrant crypt foci (ACF) and tumor formation in a mouse model. Five-week old ICR mice were acclimated for one week and fed different selenium diet (0.02, 0.1, and 0.5 ppm) for 12 weeks. Animals received three intraperitoneal injections of azoxymethane (10 mg/kg B.W. in saline for 3 weeks), followed by 2% dextran sodium sulfate in the drinking water for a week. There were four experimental groups, including a normal control group and three different selenium levels groups. After sacrifice, the total numbers of aberrant crypt (AC) and ACF were measured in the colonic mucosa after methylene blue staining. The number of tumors was noted for tumor incidence. Liver selenium concentration was measured using ICP-AES method. Gutathione peroxidase (GPx) activity was determined using a GPx assay kit in the liver and colon. TUNEL assay and proliferating cell nuclear antigen (PCNA) staining were performed to examine the cell apoptosis and cell proliferation, respectively. Immunohistochemistry of $\beta$-catenin was also performed on the mucous membrane tissue of colon. The activity of GPx in the liver and colon was decreased in the selenium-deficient diet group while it was increased in the selenium-overloaded diet group. Apoptotic positive cells were increased in the selenium-overloaded diet group but decreased in the selenium-deficient diet group. PCNA staining area was decreased in the selenium-overloaded diet group. In addition, the $\beta$-catenin protein level in the selenium-deficient diet group was increased but decreased in the selenium-overloaded diet group. These results indicate that dietary selenium might exert a modulating effect on colon cancer by inhibiting the development of ACF and colon tumor formation in this mouse model.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.26-35
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• 2006

Background: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-${\kappa}B$ and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. Materials and Methods: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-${\kappa}B$ $cis$-elements. C57BL/6 NF-${\kappa}B^{EGFP}$ mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-${\kappa}B$ activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis. Results: A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-${\kappa}B$ activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells. Conclusions: These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.

• Korean Journal of Acupuncture
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• v.31 no.2
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• pp.56-65
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• 2014

Objectives : The purpose of this study is to compare the effects of laser acupuncture to the 830 nm on the five transport points with the spleen meridian for treatment to intestinal disease in rat with dextran sulfate sodium(DSS)-induced colitis. Methods : Colitis was induced by DSS for 20 days. The laser therapy on the five transport points of spleen meridian (Laser Well Point-SP1(L-WE), Laser Brook Point-SP2(L-BR), Laser Stream Point-SP3(L-ST), Laser River Point-SP5(L-RI) and Laser Sea Point-SP9(L-SE) was practiced twice a week for 5 times. Colon length was measured using a measuring point. Histological evaluation of colitis was conducted by hematoxylin and eosin(H&E) staining. Reverse transcription polymerase chain reaction(RT-PCR) was determined using western blotting and quantitative reverse-transcriptase polymerase chain reaction, respectively. Results: Colon length increased significantly L-BR and L-ST points after 5 times of therapy. Damage to the colonic mucosa is an integral feature of the DSS model, so control colonic mucosa tissue was damaged in the areas of ulceration resulting in complete epithelial loss. However histological damage decreased on the epithelial lining at all points. Cyclooxygenase(COX)-2 concentrations decreased in all points groups and Interferon(IFN)-${\gamma}$ increased in L-WE, L-BR, L-RI and L-SE points but L-ST was decreased when compared with control. White blood cell(WBC) and neutrophils(NE) decreased after the fifth acupuncture on the all points. But hemoglobin(HGB) increased after the fifth acupuncture on the L-WE, L-BR, L-ST and L-RI points. Also Mean corpuscular hemoglobin(MCH) and Mean corpuscular hemoglobin concentration(MCHC) decreased after the fifth acupuncture on the all points. Conclusions: The present study indicated that five transport points of the spleen meridian can prevent the development of DSS-induced colitis in rat. Thereby suggesting that should be available for decreasing DSS-induced inflammation in a colonic mucosa of tissue.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.863-876
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• 2017

Objectives: The aim of this experimental study was to evaluate the anti-neoplastic and anti-inflammatory effects of single and mixed extracts of Ulmus davidiana (UD) and Oldenlandia diffusa (OD) on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic neoplasms in mice. Methods: AOM/DSS induces colitis-associated colonic neoplasms in mice. Mice were divided into seven groups: normal-no inducement and no treatment; control-colonic neoplasms with no treatment; UD-colonic neoplasms and treatment with UD; OD-colonic neoplasms and treatment with OD; UD1+OD1-colonic neoplasms and treatment with UD1 and OD1. UD1+OD2-colonic neoplasms and treatment with UD1 and OD2; UD2+OD1-colonic neoplasms and treatment with UD2 and OD1. Single and mixed preparations of UD and OD were applied to mice for six weeks. The colon length and weight and histopathologic changes of colon tissue were observed. Serum pro-inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of Bax, Bcl-2, and interferon-gamma ($INF-{\gamma}$) were measured by RT-PCR. Results: The colon length was significantly increased in OD, UD1+OD2, and UD2+OD1 mice, and the colon weight was significantly decreased in OD and UD1+OD2 mice. The morphological change of colon epithelial cells was more suppressed in complex-treatment groups than in single-treatment groups. The inhibitory effect on inflammatory cell invasion was especially shown in UD1+OD2 mice. The serum level of the pro-inflammatory $TNF-{\alpha}$ was decreased in all complex-treatment groups, and the IL-6 level was decreased in UD1+OD1 mice. Single-treatment groups had an increase in the mRNA expression of the pro-apoptosis regulator Bax, and UD2+OD1 decreased the mRNA expression of the anti-apoptosis regulator Bcl-2. The mRNA expression of $INF-{\gamma}$ associated with inflammation was decreased in OD and UD1+OD2 mice. Conclusions: This study suggests that single and mixed extracts of Ulmus davidiana and Oldenlandia diffusa have anti-neoplastic and anti-inflammatory effects on AOM/DSS-induced colonic neoplasms in mice. Therefore, we conclude that UD, OD, and a mixture of UD and OD are potential therapeutic agents for colitis-associated colonic neoplasms.

• Korean Journal of Food Science and Technology
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• v.46 no.1
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• pp.61-67
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• 2014

This study aimed to investigate the anti-inflammatory activities of raw (P) and roasted (RP) Perilla frutescens Britton (perilla) seeds in RAW 264.7 macrophages and an ulcerative colitis mouse model. In lipopolysaccharide-treated RAW 264.7 cells, treatment with ethanol extract of P at the concentrations of 75 and $150{\mu}g/mL$ decreased nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) levels to 48-85% of the control (p<0.01). Treatment with RP extract exhibited similar effects on NO, IL-6, and TNF-${\alpha}$, decreasing those levels to 51-84% of the control (p<0.01). In dextran sulfate sodium-treated ulcerative colitis mice, dietary treatment with 1% RP for 7 days decreased the colonic levels of prostaglandin $E_2$ and leukotriene $B_4$ to 34% and 58% of the control, respectively (p<0.05). Dietary P treatment, however, did not decrease those levels significantly. These results indicate that roasted perilla seed exerts anti-inflammatory activity both in vitro and in vivo.

• Nutrition Research and Practice
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• v.9 no.6
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• pp.619-627
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• 2015

BACKGROUND/OBJECTIVES: Colitis is a serious health problem, and chronic obesity is associated with the progression of colitis. The aim of this study was to determine the effects of natural raw meal (NRM) on high-fat diet (HFD, 45%) and dextran sulfate sodium (DSS, 2% w/v)-induced colitis in C57BL/6J mice. MATERIALS/METHODS: Body weight, colon length, and colon weight-to-length ratio, were measured directly. Serum levels of obesity-related biomarkers, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), insulin, leptin, and adiponectin were determined using commercial kits. Serum levels of pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 were detected using a commercial ELISA kit. Histological study was performed using a hematoxylin and eosin (H&E) staining assay. Colonic mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR assay. RESULTS: Body weight and obesity-related biomarkers (TG, TC, LDL, HDL, insulin, leptin, and adiponectin) were regulated and obesity was prevented in NRM treated mice. NRM significantly suppressed colon shortening and reduced colon weight-to-length ratio in HFD+DSS induced colitis in C57BL/6J mice (P < 0.05). Histological observations suggested that NRM reduced edema, mucosal damage, and the loss of crypts induced by HFD and DSS. In addition, NRM decreased the serum levels of pro-inflammatory cytokines, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 and inhibited the mRNA expressions of these cytokines, and iNOS and COX-2 in colon mucosa (P < 0.05). CONCLUSION: The results suggest that NRM has an anti-inflammatory effect against HFD and DSS-induced colitis in mice, and that these effects are due to the amelioration of HFD and/or DSS-induced inflammatory reactions.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.833-842
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• 2020

Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

• Journal of Food Hygiene and Safety
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• v.26 no.4
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• pp.388-397
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• 2011

Selenium (Se) is known to prevent from several cancers, while iron (Fe) is known to be associated with high risk of cancers. The role of Se on colon carcinogenesis was investigated in an animal model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in low Fe mice. Six-week old ICR mice fed on a low Fe diet (4.5 ppm Fe; generally 10 times lower than normal Fe) with three different Se (0.02, 0.1 or 0.5 ppm) levels for 24 weeks. The animals received weekly three ($0{\sim}2^{nd}$ weeks) i.p. injections of AOM (10 mg/kg RW), followed by 2% DSS with drinking water for 1 week to induce the colon cancer. There were five experimental groups including vehicle, positive control (normal Fe level, AOM/DSS), Low Fe (LFe) + AOM/DSS+Low Se (LSe), LFe + AOM/DSS + medium Se (MSe) and LFe + AOM/DSS + high Se (HSe) groups. HSe group showed a 66.7% colonic tumor incidence, MSe group showed a 69.2% tumor incidence, and LSe group showed a 80.0% tumor incidence. The tumor incidence was negatively associated with Se levels of diets. Tumor multiplicity in Hse group was significantly low compared to the other groups (p < 0.05). With increasing Se levels of diets, the primary anti-proliferating cell nuclear antigen (PCNA)-positive cells were decreased and apoptotic bodies were increased in a dose-dependent manner. Se-dependent glutathione peroxidase activity and its protein level were dependent on the levels of Se of diets. Malondialdehyde level in liver was lowest in Hse group among experimental groups. These findings indicate that dietary Se is chemopreventive for colon cancer by increasing antioxidant activity and decreasing cell proliferation in Fe-deficient mice.