• 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.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.52-58
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• 2011

The inhibitory effect of Chung-Jang-Hwan (C-mix) consisted of Geranium nepalense subsp. thunbergii, Saururus chinensis, and Rubus coreanus were investigated in dextran sulfate sodium (DSS)-induced colitic mice by microarray analysis. Treatment with Cmix improved colitic symptoms, including colon shortening and myeloperoxidase activity. Treatment with DSS alone upregulated the expression levels of inflammation-related genes, including IL-$1\beta$, IL-6, CCL2, CCL4, CCL5, CCL7, CCL8, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1 in mice. However, treatment with C-mix inhibited the expression levels of inflammation-associated genes induced by DSS. The increased expression levels of COX-2 and IL-$1\beta$, representative inflammatory genes, were confirmed by a quantitative realtime polymerase chain reaction analysis. These results indicate that C-mix may ameliorate colitis by the inhibitory regulation of inflammation-associated genes.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.655-663
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• 2020

Background: Korean Red Ginseng is known to exhibit immune-enhancing and anti-inflammatory properties. The immune-enhancing effects of the nonsaponin fraction (NSF) of Korean Red Ginseng have been studied in many reports. However, the gastroprotective effect of this fraction is not fully understood. In this study, we demonstrate the activities of NSF for gastrointestinal protection and its related critical factor. Methods: The in vitro and in vivo regulatory functions of NSF on cyclooxygenase-1 (COX-1) messenger RNA and protein levels were examined by reverse transcription polymerase chain reaction and immunoblotting analyses. Gastroprotective effects of NSF were investigated by histological score, gastric juice pH, and myeloperoxidase activity on indomethacin-induced, cold stress-induced, and acetylsalicylic acid-induced gastritis and dextran sulfate sodium-induced colitis in in vivo mouse models. Results: NSF did not show cytotoxicity, and it increased COX-1 messenger RNA expression and protein levels in RAW264.7 cells. This upregulation was also observed in colitis and gastritis in vivo models. In addition, NSF treatment in mice ameliorated the symptoms of gastrointestinal inflammation, including histological score, colon length, gastric juice pH, gastric wall thickness, and myeloperoxidase activity. Conclusion: These results suggest that NSF has gastroprotective effects on gastritis and colitis in in vivo mouse models through COX-1 upregulation.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.122-122
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• 2019

Protaetia brevitarsis (PB) extracts has been traditionally used as medicinal stuff to treat blood stasis, occlusion of menstruation, tetanus and liver cancer in Asian countries (Korea, Japan, China, Taiwan, India and Myanmar). Especially, Donguibogam, which is traditional korean medicinal book, described the PB extracts as traditional medicine to treat hepatic diseases and vascular disorders. The PB extracts has been considered as highly nutritional food. The major constituents of PB extracts are rich in protein, healthy fats, iron, calcium. Recent studies announced that PB extracts has hepatoprotective effect and anti-microbacterial effect. However, the effect of PB on ulcerative colitis has not been uncovered yet. The aim of this study was to examine the anti-inflammatory effect of PB extracts in dextran sulfate sodium (DSS)-induced colitis mice model. Cytotoxicity of PB was determined by MTT assay and the antiinflammatory effect of PB extract was investigated by measuring nitric oxide (NO) production. PB extracts did not show any cytotoxicity. AIso, PB extracts supressed NO production in LPS-stimulated mice peritoneal macrophages. To determine whether PB could be an effective treatment on ulcerative colitis, DSS was administered in BALB/c mice for 10 days. PB extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. These findings indicated the possibility of PB as a therapeutic agent on ulcerative colitis.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1478-1487
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• 2019

Ulcerative colitis (UC), a chronic inflammatory bowel disease, substantially impacts patients' health-related quality of life. In this study, an effective strategy for discovering high-efficiency probiotics has been developed. First, in order to survive in the conditions of the stomach and intestine, high bile salt-resistant and strong acid-resistant strains were screened out from the fecal flora of healthy adults. Next, the probiotic candidates were rescreened by examining the induction ability of IL-10 (anti-inflammatory factor) production in dextran sodium sulfate (DSS)-induced colitis mice, and Lactobacillus sakei 07 (L07) was identified and selected as probiotic P. In the end, fourteen bifidobacterium strains isolated from stools of healthy males were examined for their antimicrobial activity. Bifidobacterium bifidum B10 (73.75% inhibition rate) was selected as probiotic B. Moreover, the colonic IL-6 and $TNF-{\alpha}$ expression of the DSS-induced colitis mice treated with L. sakei 07 (L07) - B. bifidum B10 combination (PB) significantly decreased and the IL-10 expression was up-regulated by PB compared to the DSS group. Furthermore, Bacteroidetes and Actinobacteria decreased and Firmicutes increased in the DSS group mice, significantly. More interestingly, the intestinal flora biodiversity of DSS colitis mice was increased by PB. Of those, the level of B. bifidum increased significantly. The Bacteriodetes/Firmicutes (B/F) ratio increased, and the concentration of homocysteine and LPS in plasma was down-regulated by PB in the DSS-induced colitis mice. Upon administration of PB, the intestinal permeability of the the DSS-induced colitis mice was decreased by approximately 2.01-fold. This method is expected to be used in high-throughput screening of the probiotics against colitis. In addition, the L. sakei 07 - B. bifidum B10 combination holds potential in UC remission by immunomodulatory and gut microbiota modulation.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.107-107
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• 2019

Ulcerative colitis (UC) is one of inflammatory bowel disease (IBD), characterized by chronic inflammatory response and dysregulation of immune function. The severity of US has been influenced by environmental factors and food habit. The immune modulatory, anti-inflammatory and steroidal medicine have been used for the treatment of UC. However, long-term administration of those medicine is accompanied with side-effect. So, it is necessary to develop the non side-effect medicine using natural product. Prebiotics influences intestinal condition and food consumption. The heredity, immunity and environmental condition are related with occurrence of UC. In recent study, UC patients had lower level of prebiotics such as Lactobacillus and Bifidobacterium compared with healthy people. Also, previous study announced that imbalance of enteric flora aggravates the severity of UC. The effectiveness of probiotics might affect colon ability and viable bacteria also could promote the proliferation of beneficial intestinal bacteria. Prebiotics, such as herbal medicine, could lead to balance of intestinal bacteria or increase beneficial bacteria. So, proper choice of herbal medicine could control the intestinal condition. This study aimed to investigate the effect of mixture of probiotics and prebiotics (synbiotics) on dextran sulfate sodium (DSS)-induced UC in vivo. The synbiotics consist of Lactobacillus buchneri, Polymnia sonchifolia and Glycine max Merr. in this study. To evaluate the effect of synbiotics, 3% DSS was administered in BALB/c mice and synbiotics was daily administered for experimental days. The administration of synbiotics regulated colon length shortening, body weight change and disease activity index effectively. Also, extract of synbiotics upregulated survival ability of Lactobacillus buchneri in gut condition. These results suggest that mixture of probiotics and prebiotics, called as synbiotics, could influence intestinal condition also regulate the colon disease. Synbiotics might be a therapeutic agent for treatment of UC.