• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1807-1810
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• 2014

Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 ${\mu}M$ for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2689-2698
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• 2013

Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

• Journal of the Korean Applied Science and Technology
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• v.35 no.2
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• pp.509-518
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• 2018

The purpose of this study was myokine product and role with physical activity and literature review. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular disease, colon cancer, dementia and even depression. And myokine has been regarded an important factor of exercise training and brain growth factor for the prevention of Alzheimier's disease. During exercise the release of anti-inflammatory myokine from contracting muscle controled the metabolic response, and IL-4, IL-6, IL-7, IL-10, and IL-15 controled muscle hypertrophy, myogenesis and angiogenenesis. IL-6 promoted the lipid metabolism through AMPK activation. IL-1Ra, IL-10 and sTNF-R inhibited $TNF-{\alpha}$ as the pro-inflammatory cytokine. IL-15 increased the releasing volume from contracting muscle, and promoted the anabolic factor of muscle growth. IL-7 and IL-8 activated the angiogenesis through the more activation of C-X-C receptor signal transmission.

• Korean Journal of Veterinary Service
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• v.27 no.4
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• pp.345-354
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• 2004

Two cases of classical swine fever (CSF) disease have broken out in Cheolwon (7 April, 2002). The suspected pig herds were huddled together because of high fever (over $40^{\circ}C$) and showed remarkable decrease of the leukocytes. The staggering gait related to posterior weakness, constipation and lethargy, hyperemia, hemorrhagic lesions (on the skin, muzzle, ears, limbs, tail and inner part of legs) and conjunctivitis with dirty streaks below the eyes were observed. The inflammation in the lung, infarction in the spleen, swelling and hemorrhage in lymph nodes, kidney, intestine, heart and cheese like purulent inflammation of the tonsil were observed. The ulcers of the colon were also detected. Several clinical and laboratory techniques including blood test, histo-pathological examinations, indirect fluorescent antibody (IFA) test and RT-PCR test were applied to diagnose the disease. Inoculation test on PK-15 cell was also performed. The necrosis of the lymphatic cells and infiltration of the vessel circumferential cells in the brain and lymph organs were commonly viewed. The proliferation of the glia cell (gliosis) in the lymph was particular. Cytopathogenic effect (CPE) and specific fluorescent-bright-green areas (with IFA) appeared in PK-15 cells inoculated with suspected blood plasma. The IFA test on the epithelial and mucous membrane cells of tonsil was positive. RT-PCR technique required more working hours and labor than other techniques in this examination but it was useful because of the sensitivity to the CSF viral gene.

• International Journal of Internet, Broadcasting and Communication
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• v.13 no.2
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• pp.145-155
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• 2021

With the recent rapid improvement in the standards of life and westernization of dietary lifestyles, the consumption of high-calorie diets such as high-fat and high-protein red meat and instant foods has increased, while less vegetables containing dietary fiber are consumed. In addition to that, stress, erroneous dietary behaviors, and contaminated environments are linked to the risk of developing ulcerative colitis, which is on the rise. Another cause of ulcerative colitis is that involve laxative abuse, including repeated, frequent use of laxatives, and include such conditions as deteriorated bowel function, irritable bowel syndrome, diarrhea, intestinal inflammation, etc. The present study aimed to investigate the comparative evaluation of pharmacological efficacy between sulfasalazine alone and combination with herbal medicine on dextran sodium sulfate (DSS)-induced UC in mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis. Animals were divided into five groups (n = 9): group I-normal group, group II-DSS control group, group III-DSS + sulfasalazine (30 mg/kg), group IV-DSS + sulfasalazine (60 mg/kg), group V-DSS + sulfasalazine (30 mg/kg) + Radish Extract mixture (30 mg /kg) (SRE). DSS-treated mice developed symptoms similar to those of human UC, such as severe bloody diarrhea and weight loss. SRE supplementation, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, SRE treatment significantly reduced the expression of pro-inflammatory signaling molecules through suppression both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, and prevented the apoptosis of colon. Moreover, SRE administration significantly led to the up-regulation of antioxidant enzyme including SOD and Catalase. This is the first report that Radish extract mixture combined with sulfasalazine protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazine.

• The Journal of Internal Korean Medicine
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• v.45 no.4
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• pp.681-699
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• 2024

Objectives: This study was designed to verify the effects of Mannyeon-hwan (MNH) on acetic acid-induced ulcerative colitis in rats. Methods: Ulcerative colitis was induced in male Sprague-Dawley rats weighing approximately 250 g by injecting acetic acid through the anus. Rats were classified into four groups: normal group, control group (acetic-acid, AA), low concentration group (AA+MNH(L)), and high concentration group (AA+MNH(H)). Body weight, visual evaluation of the colonic mucosa, anatomical histological changes, and changes in the expression of proteins in colon tissue were compared and analyzed. Results: Compared to the control group, the MNH groups showed significant recovery from weight loss and mucosal damage. The expression of inflammatory proteins such as TNF-α, IL-6, IL-1β, NF-κB p65, MPO, and COX-2 were significantly decreased in the MNH groups compared to those in the AA group. In the MNH groups, significant changes in proteins involved in apoptosis such as caspase-3, BAX, and Bcl-2 were observed compared to those in the AA group. Additionally, changes in the expression of TNF-α, IL-6, IL-1β, NF-κB p65, BAX, and Bcl-2 were greater in the MNH(H) group than those in the MNH(L) group. Conclusion: Mannyeon-hwan was found to be effective in suppressing inflammation of the colonic mucosa in ulcerative colitis, inhibiting the expression of inflammation-related proteins, and suppressing damage to the colonic mucosa by regulating the expression of apoptosis-related proteins.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• The Korean Journal of Physiology and Pharmacology
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• v.69 no.3
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• pp.359-371
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• 2018

Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

• Food Science and Biotechnology
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• v.15 no.5
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• pp.799-804
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• 2006

Ingestion of green tea has been shown to decrease prostaglandin $E_2$ levels in human colorectum, suggesting that tea constituents modulate arachidonic acid metabolism. In the present study, we investigated the effects of four purified green tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), and (-)-epicatechin-3-gallate (ECG), on the catalytic activity of cytosolic phospholipase $A_2$ ($cPLA_2$) and release of arachidonic acid and its metabolites from intact cells. At $50\;{\mu}M$, EGCG and ECG inhibited $cPLA_2$ activity by 19 and 37%, respectively, whereas EC and EGC were less effective. The inhibitory effects of these catechins on arachidonic acid metabolism in intact cells were much more pronounced. At $10\;{\mu}M$, EGCG and ECG inhibited the release of arachidonic acid and its metabolites by 50-70% in human colon adenocarcinoma cells (HT-29) and human esophageal squamous carcinoma cells (KYSE-190 and 450). EGCG and ECG also inhibited arachidonic acid release induced by A23187, a calcium ionophore, in both HT-29 and KYSE-450 cell lines by 30-50%. The inhibitory effects of green tea catechins on $cPLA_2$ and arachidonic acid release may provide a possible mechanism for the prevention of human gastrointestinal inflammation and cancers.

• Korean Journal of Food Science and Technology
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• v.52 no.5
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• pp.482-486
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• 2020

Cases of inflammatory bowel diseases including ulcerative colitis are increasing in Korea and development of non-steroidal anti-inflammatory drugs (NSAIDs) are widely investigated. Natural products with anti-inflammatory properties are rising as safe candidates for NSAIDs. The extract of turmeric or puffed turmeric mixed with herbal extract (goji berry, liquorice, lycium root, and dong quai) was treated to acute colitis mice by oral gavage. The symptoms of colitis, i.e., body weight loss, fecal score, and shortened colon length, were significantly attenuated by puffed turmeric extract with the herbal extract. Non-puffed turmeric extract with herbal extract, however, exhibited a very marginal recovery. Tissue culture supernatant of colons further revealed that both puffed turmeric and non-puffed turmeric extracts with herbal extract suppressed pro-inflammatory cytokine production at a comparable level. These results indicate that puffing is a simple and promising process of turmeric for enhancement of anti-inflammatory properties.