• The Journal of Internal Korean Medicine
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• v.36 no.3
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• pp.284-296
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• 2015

Objectives: The purpose of this study was to examine the effects of Ohmae-hwan (OMH) and Mume Fructus (MF) on inflammatory bowel disease (IBD). Methods: Mice were divided into 4 groups: a normal group, control group, MF group, and OMH group. Three groups, excluding the normal group, were fed a 5% solution of dextran sulfate sodium (DSS) in water for 10 days to induce inflammatory bowel disease. From the fourth day of DSS treatment, the control group was given distilled water only, the MF group was given MF powder in distilled water, and the OMH group was given dried OMH extract powder in distilled water for 7 days. Results: For each animal, changes in body weight, colon length, and component levels in blood and colon tissues after each treatment were noted. The weight in the control group and MF group decreased slightly compared with that in the OMH group, and the colon length in the MF group and OMH group was more than that in the control group. TNF-α and WBC were decreased in both the MF group and the OMH group. RBC was increased in the OMH group, like in the normal group, compared with the control group and MF group. Hb and PLT of each group were not significantly different. Regarding changes in the colon tissues, both the MF group and OMH groups recovered similar to the normal group. Conclusions: Thus, treatment with OMH and MF seems to be effective against inflammatory bowel disease, and OMH is likely to increase body weight and induce RBC recovery better than MF.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.3
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• pp.16-25
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• 2018

Objectives The purpose of this study is to investigate the anti-inflammatory effect of Lonicera Japonica-Glycyrrhiza Uralensis decoction extracts (LGE) on ulcerative colitis in children and adolescents. Methods Colitis was induced by DSS (Dextran Sulfate Sodium) in C57BL/6 mice. The sample mice were divided into group of four. The mice in the control group were not inflammation-induced. The control group was composed of untreated ulcerative colitis elicited mice. The mice in the experimental group were administered with Pentasa and another experimental group mice were treated with LGE after colitis elicitation. The effects on ulcerative colitis were evaluated by the morphological changes of colonic mucosa, decrease in the effect of pro-inflammatory cytokines ($TNF-{\alpha}$ and $NF-{\kappa}B$) and inflammatory cytokines (iNOS and COX-2) in the mucosa. Results LGE showed protective effects in DSS induced ulcerative colitis. LGE inhibited shortening of colon length and relieved the hemorrhagic erosion in colonic mucosa. LGE decreased pro-inflammatory cytokines ($TNF-{\alpha}$ and $NF-{\kappa}B$) and inflammatory cytokines (iNOS and COX-2). According to the GC/MS analysis, N-methyl pyrrolidone (NMP) was identified. Conclusions The result shows the clinical efficacy of LGE and demonstrates possible treatment options for ulcerative colitis. Further investigations for biological activity and chemical analysis of LGE will be needed.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.165-173
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• 1997

This study was conducted to investigate the effect of DA-9601, an extract of Artemisiae Herba, which is known to possess mucoprotective action either by free radical scavenging effect or increase of mucus secretion, against animal models of inflammatory bowel disease (IBD) induced by trinirobenzene sulfonic acid (TNBS) or other noxious agents. Experimental colitis was induced by intracolonic administration of TNBS in 50% ethanol, or 1 ml of 7% acetic acid solution (AA), by subcutaneous injection of indomethacin (INDO) in rats, or by supplementing drinking water with 5% dextran sodium sulfate (DSS) in albino mice. DA-9601 was treated orally for 4 to 7 days. Animals were euthanized 1 day after the last treatment for morphological and biochemical analysises. All the noxious agents including TNBS, AA, INDO and DSS elicited severe colitis. The animals treated with DA-9601 showed a consistent, dose-related reduction in the severity of colitis, grossly and histologically. The reduction was significant (p<0.05) after administration of DA-9601 at dose range of 10 mg/kg or above. In TNBS-induced colitis, the rats receiving DA-9601 showed significantly decreased mucosal myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBA-RS), when compared to control and mesalazine groups. Mucosal proinflammatory cytokine levels were also decreased after DA-9601 treatment. In conclusion, DA-9601 ameliorated macroscopic and histologic scores in experimental colitis either through decreasing oxidative stress or by attenuating cytokines involved in inflammation. DA-9601 could be a promising drug for the therapy of IBD.

• Journal of Microbiology and Biotechnology
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• v.30 no.8
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• pp.1132-1141
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• 2020

Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.137-147
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• 2020

Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.

• Biomedical Science Letters
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• v.20 no.4
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• pp.227-236
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• 2014

Ulcerative colitis (UC) is a serious gastrointestinal tract disease characterized by recurrent chronic inflammation and mucosal damage of the gastrointestinal tract. The conventional therapies of choice are anti-inflammatory agents, steroids and anti-TNF-${\alpha}$ therapy. However, inherent limitations in these therapies have steered many UC patients to supplement existing therapies with alternative medicinal products. In the current study, we tested the efficacy of Gingko bilola extract (EGb 761) in abating colonic inflammation in a DSS-induced murine model of colitis. C57BL/6 mice were administered 2% DSS in the drinking water for 7 days, then regular water for 7 days, and then 2% DSS for an additional 7 days. EGb 761 (1 mg/dose) was oral gavaged daily for the duration of the experiment. At the termination of the experiment, mice treated with EGb+DSS showed higher body weight, lower spleen weight and longer colon length compared to mice treated with DSS alone. HE-stained colon tissues also exhibited less histologic inflammation in mice treated with EGb+DSS mice compared to mice treated with DSS alone. The serum levels inflammatory cytokines, KC and TNF-${\alpha}$, were also decreased in mice treated with EGb+DSS compared to mice treated with DSS alone. Finally, addition of EGb 761 to TNF-${\alpha}$ treated colonic cell line (HT29/c1) decreased secretion of IL-8 in vitro. These results collectively suggest that EGb 761 abates induction of colitis in DSS-induced model of colitis in mice.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4135-4139
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• 2013

Inflammation is potential risk factor of various human malignancies. Inflammatory bowel syndromes such as ulcerative colitis are well known as risk factors for colon cancer. Here, we examined enhancing effects of dextran sulfate sodium (DSS)-associated inflammation on X-irradiation induced colonic tumorigenesis in Min and wild-type (WT) mice. Animals were X-irradiated at 1.5 Gy at 5 weeks of age (at 0 experimental week) and 2% DSS in drinking water was administered at 5 or 11 experimental weeks. Mice were sacrificed at 16 weeks and incidence and multiplicity of colonic tumors were assessed. Incidence of colonic tumors in Min mouse was increased from 33.3% to 100% (p<0.05) with X-irradiation alone, whereas no tumors were developed in WT mice. In DSS-treated Min mice, X-irradiation increased the number of colonic tumors. Total number of colonic tumors was increased 1.57 times to $30.7{\pm}3.83$ tumors/mouse with X-irradiation+DSS at 5 weeks comapared to $19.6{\pm}2.9$ in corresponding DSS alone group (p<0.05). When the duration of inflammation was compared, longer period of DSS effect promoted more colonic tumorigenesis. Collectively, we conclude that X-irradiation and DSS-induced inflammation act synergistically for colonic tumorigenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5587-5592
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• 2014

Aloe-emodin (AE), a natural anthraquinone compound, has been reported to exhibit anticancer activity in various cancer cell lines and anti-inflammatory effects in murine macrophages. In the present study, we investigated the cancer chemopreventive effects of AE in an Apc-deficient Min mouse model. In the first experiment, male Min mice were fed a basal diet or diets containing 5 ppm AE and 10 ppm AE for 12 weeks. The dietary administration of 5 ppm AE significantly reduced the number of colorectal tumors. In a second experiment, we investigated the effects of AE on colitis-related colon carcinogenesis in Min mouse treated with dextran sodium sulfate (DSS). Female Min mice were administered 1% DSS in their drinking water for 7 days. AE was given to mice in their diet at a dose of 5 or 50 ppm for 5 weeks. Feeding with AE significantly reduced the number of colorectal tumors. When proliferation of cells in normal-appearing colonic mucosa was assessed by monoclonal anti-rat Ki-67 antibody (MIB-5) immunohistochemistry in experiments 1 and 2, the AE treatment significantly decreased the mean MIB-5-labeling index. These results suggest that the dietary administration of low-dose AE may have chemopreventive effects against development of colorectal tumors in Min mice, possibly in part by reducing cell proliferation in colorectal mucosa.

• BMB Reports
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• v.48 no.7
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• pp.419-425
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• 2015

Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis. [BMB Reports 2015; 48(7): 419-425]

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.379-389
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• 2018

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines $TNF-{\alpha}$ and IL-6 and inflammatory lipid mediators, prostaglandin $E_2$ and leukotriene $B_4$. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed $I{\kappa}B$ phosphorylation, nuclear translocation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-13 and also hindered phosphorylation of $NF-{\kappa}B$ and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of $TNF-{\alpha}$ and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.