• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.71-78
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• 2020

Lactobacillus sakei S1 strongly inhibits the expression of interleukin (IL)-6 and IL-1β in lipopolysaccharide-induced peritoneal macrophages by a mechanism for which lactic acid bacteria from kimchi that inhibit tumor necrosis factor-alpha (TNF-α) were isolated. Therefore, we further evaluated the protective effect of this strain on the colitis mouse model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS significantly elevated myeloperoxidase (MPO) expression, macroscopic scores, and colon shortening. Oral L. sakei S1 administration resulted in reduction of TNBS-induced loss in body weight, colon shortening, MPO activity, expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB). L. sakei S1 inhibited the expression of inflammatory cytokines IL-1β, IL-6 and TNF-α, induced by TNBS, but enhanced IL-10 expression. L. sakei S1 showed resistance to artificial digestive juices and adherence to intestinal epithelial Caco-2 cells. Thus, L. sakei S1 may inhibit the NF-κB pathway and be used in functional food to treat colitis.

• Journal of Microbiology and Biotechnology
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• v.33 no.8
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• pp.1057-1065
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• 2023

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

• Korean Journal of Veterinary Research
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• v.47 no.1
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• pp.19-24
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• 2007

The cause and pathogenesis of inflammatory bowel disease remain unknown and no definitetherapy exists until now. The present study was conducted to investigate the anti-inflammatory effectsof a herbal preparation (HemoHIM) in colitis induced by 30 mg of trinitrobenzene sulfonic acid (TNBS)in rats. Sprague-Dawley rats were divided into 5 groups. Each group was treated with 1 mg ofHemoHIM/ml of drinking water, 4 mg of HemoHIM/ml of drinking water, 50 mg of HemoHIM/kgof body weight (i.p. once every other day) or 10 mg/kg of HemoHIMof body weight (i.p. onceevery other day) from the next day. After 2 weeks, rats were sacrificed and morphologic featuresof colons were examined. Ulceration, adhesion, thickening and dilatation were noticed in the colonicmucosa after TNBS instillation. Intraperitoneal injection of HemoHIM (50 and 100 mg/kg of bodyweight) showed the anti-inflammatory effect on adhesion, thickening, dilatation, ulceration, and theinhibition effect on damage score by 72.7% and 90.9%, respectively. Histologically, the colon of TNBS-treated rat showed inflammatory cell infiltration by polymorphonuclear cells, multiple erosive lesionsignificant improvement in these symptoms. The results obtained suggest marked anti-inflamatoryactivity of the HemoHIM at the dose levels examined.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.310-317
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• 2006

We investigated the effects of trinitrobenzene sulfonic acid (TNBS), an amino-group reagent, on the human ether-a-go-go-related gene (HERG) $K^+$ channels expressed in Xenopus oocytes. TNBS neutralizes the positively charged amino-groups of peptide N-terminal and lysine residues. External application of TNBS at 10 mM for 5 min irreversibly shifted the curves for currents at the end of the pulse and tail currents of HERG to a more negative potential and decreased the maximal amplitude of the $I_{tail}$ curve $(I_{tail,max})$. TNBS had little effect on either the activated current-voltage relationship or the reversal potential of HERG current, indicating that TNBS did not change ion selectivity properties. TNBS shifted the time constant curves of both activation and deactivation of the HERG current to a more hyperpolarized potential; TNBS's effect was greater on channel opening than channel closing. External $H^+$ is known to inhibit HERG current by shifting $V_{1/2}$ to the right and decreasing $I_{tail,max}$. TNBS enhanced the blockade of external $H^+$ by exaggerating the effect of $H^+$ on $I_{tail,max}$, not on $V_{1/2}$. Our data provide evidence for the presence of essential amino-groups that are associated with the normal functioning of the HERG channel and evidence that these groups modify the blocking effect of external $H^+$ on the current.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.43-50
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• 2015

It has been shown that the extracts including eupatilin and quercetin-3-${\beta}$-D-glucuronopyranoside had mucoprotective effects on the esophagus and stomach through their antioxidant activities. This study was designed to investigate the anti-inflammatory effect of these flavonoid compounds in an animal model of inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulfonic acid. Experimental colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid. Extracts including eupatilin or quercetin-3-${\beta}$-D-glucuronopyranoside were orally administered to animals 48, 24, and 1 h prior to the induction of colitis and then again 24 h later. The animals were sacrificed 48 h after by 2,4,6-trinitrobenzene sulfonic acid treatment and the macroscopic appearance of the colonic lesions was scored in a blinded manner on a scale of 1 to 10. The inflammatory response to colitis induction was assessed by measuring myeloperoxidase activity, nitric oxide production, tumor necrosis factor-${\alpha}$ expression, total glutathione levels, and malondialdehyde concentrations in the colon. The results indicated that extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside dose-dependently improved the morphology of the lesions induced by 2,4,6-trinitrobenzene sulfonic acid and reduced the ulcer index accordingly. In addition, rats receiving extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside showed significantly decreased levels of mucosal myeloperoxidase activity, nitric oxide production, tumor necrosis factor-${\alpha}$ expression, and malondialdehyde levels, and increased total glutathione levels. Extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside ameliorated the inflammatory response and colonic injury in acute colitis by decreasing oxidative stress and neutrophil activation. Extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside may inhibit acute colitis.

• Journal of Microbiology and Biotechnology
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• v.24 no.10
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• pp.1438-1444
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• 2014

Lactic acid bacteria (LAB) are probiotics that provide numerous beneficial effects on the host body, especially on the intestine. Combining several strains of LAB, we prepared a formulation containing four different LAB and studied its anti-inflammatory activity both in vitro and in vivo. The formulation significantly reduced NO production from RAW 264.7 cells treated with bacterial lipopolysaccharide, indicating that the formulation might include anti-inflammatory activity. The formulation also suppressed inflammatory change induced by trinitrobenzene sulfonic acid (TNBS) in mice, where oral or rectal administration of the formulation protected the colon tissue from the damage by TNBS. Expressions of the IL-6 and FasL genes appeared to be down-regulated by the formulation in TNBS-treated colon tissues, suggesting that the suppression of those genes may be involved in the anti-inflammatory activity of the formulation.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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• pp.224-241
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• 2010

Objectives : The aim of the current study was to investigate the effects of Sargassum (Sargassum pallidum (TURN.) C. AG.; SP) on the experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Methods : ICR mice were divided into 7 groups (NOR, CON, $SS50\times5$, $SP20\times3$, $SP50\times3$, $SP20\times5$, $SP50\times5$). TNBS processing was intrarectally applied to all experimental groups on the 3rd experiment day, except the normal group (NOR). For investigating the prophylactic effect, SP at doses of 20 mg/kg ($SP20\times5$) and 50 mg/kg ($SP50\times5$) were orally administered for 5 days. The SP at doses of 20 mg/kg ($SP20\times3$) and 50 mg/kg ($SP50\times3$) were orally administered for 3 days after the colitis induction in order to check the effect of treatment. As a positive control group, sulfasalazine 50 mg/kg ($SS50\times5$) was administrated. Macroscopic findings of epithelial tissue on mice were measured by colon length and macroscopic score. Histologic findings were also checked by crypt cell, epithelial cell, inflammatory cell and edema of submucosa. We measured the ability of SP to inhibit lipid peroxidation and myeloperoxidase activity. We also measured levels of the inflammatory markers, interleukin (IL)-$1\beta$ and cyclooxygenase-2 (COX-2), its transcription factor activation, phospho-NF-${\kappa}B$ (pp65), in the colon by enzyme-linked immunosorbent assay and immunoblot analysis. We measured activation of fecal bacterial enzyme, $\beta$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG), and hyaluronic acid. Results : Oral administration of SP on mice inhibited TNBS-induced colon shortening and myeloperoxidase activity in the colon of mice as well as IL-$1\beta$ and COX-2 expression. SP also inhibited TNBS-induced lipid peroxidation and pp65 activation in the colon of mice. SP inhibited $\beta$-glucuronidase activation and fecal hyaluronic acid degradation activation as well. Conclusions : SP could be a possible herbal candidate and preventive prebiotic agent for treating inflammatory bowel disease (IBD). Further experiments to differentiate effects of SP on IBD, such as other solutions and extracting times, might be promising.

• Toxicological Research
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• v.20 no.4
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• pp.293-298
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• 2004

Background: Crohn's disease is characterized by a chronic relapsing inflammation of the bowel. Gliotoxin has been known to play strong immunosuppressive properties, while mechanisms for its anti-inflammatory actions are not completely understood. Here, we investigated the effects of gliotoxin in trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, an animal model of Crohn's disease. Results: Gliotoxin dramatically improved clinical and histopathological symptoms in accompanied with reduced expression of TNF-$\alpha$, IL-1$\beta$, and ICAM-1 protein levels in TNBS induced colitis. Interestingly Gliotoxin induced Heme oxygenase-1 (HO-1) and the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) completely mimicked the protective effects of gliotoxin in TNBS induced colitis mice. In contrast, the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) could reverse the anti-inflammatory effects of gliotoxin and CoPPIX. Conclusions: Gliotoxin is a potential therapeutic agent targeting for the treatment of Crohn's disease by inducing HO-1.

• Korean Journal of Veterinary Research
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• v.51 no.2
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• pp.83-91
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• 2011

In this study, immunohistochemistry was used to examine the changes in the density of colonic endocrine cells - argyrophil and argentaffin cells, chromogranin A (CGA), serotonin, somatostatin and glucagon-containing cells in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Ulcerative colitis was induced by the instillation of 10 mg of TNBS into the colonic lumen through the anus. To confirm the inducement of ulcerative colitis, the macroscopic and microscopic scores as well as the colonic myeloperoxidase (MPO) activities were monitored for 8 days after TNBS instillation in the colonic lumens. In addition, the number of argyrophil and argentaffin cells, CGA, serotonin, somatostatin and glucagon-immunoreactive cells were counted in the colonic mucosa, respectively. After TNBS instillation into the lumen of the colon from the anus in rats, increases in macroscopic and microscopic scores in the colon tissues were observed along with increases in the colonic MPO activities. Therefore, ulcerative colitis was relatively well induced by the TNBS instillations. Marked decreases in the number of colonic endocrine cells were detected in the TNBS-treated animal compared to the sham control. These results suggest that colonic endocrine cells were also disrupted by TNBS-induced ulcerative colitis.

• Food Science of Animal Resources
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• v.32 no.2
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• pp.149-154
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• 2012

It is known that lactic-acid bacteria (LAB) helps keeping the intestine healthy and to enhance its immunologic competence. In addition, it is known to control the composition of the enterobacteria and the intestinal inflammatory reaction by inducing immunological enhancement. This study was performed, in a mouse model, to test the treatment and preventive effects of LAB of inflammatory bowel disease (IBD), which was induced by a blend of LAB-administering trinitrobenzene sulfonic acid (TNBS). To obtain the animal model of IBD, 2% TNBS was rectally administered once to a five-week-old male Balbc/J mouse. A probiotic combination was administered to the prevention group five times a week for eight weeks before the inducement of enteritis, and the mixture was administered to the treatment group five times a week, after the administration of TNBS. The changes in the levels of the cytokines of the lymph nodes and the tissue of the large intestine were observed, both with the naked eye and with a microscope. The observation showed that the levels of inflammatory cells, infiltration, and necrosis were much lower in the LAB-administered groups than in that of the control group. In addition, the inflammatory cytokines (e.g., TNF-${\alpha}$, IL-17A) decreased in the lymph nodes and the tissues of the large intestine. The results indicated that the administration of the combination to the animal model suppressed the inflammatory cytokines in the large intestine and in the lymph nodes, which in turn suppressed the progression of colitis.