• 동의생리병리학회지
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• 제30권5호
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• pp.338-346
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• 2016

Signal transducer and activator of transcription 3 (STAT3) is associated with various human diseases, such as cancer, auto-immune disease, and intestinal inflammation. The limited and inadequate effect of standard approaches for treating inflammatory bowel disease (IBD) has prompted to develop alternative anti-colitis agents through inhibition of STAT3. Here, we show that gallic acid (GA), a 3,4,5-trihydroxybenzoic acid, markedly reduced phosphorylation of STAT3. Among the derivatives of benzoic acids, GA showed significant inhibition on STAT3 phosphorylation. In addition, GA ameliorated the dextran sodium sulfate (DSS)-induced acute colitis as determined by the measurement of symptomatic and histological indices. The suppression of DSS-induced acute colitis by GA treatment may be related to the regulation of cytokines and growth factors. Furthermore, GA inhibited phosphorylation of STAT3 in the colon tissue of DSS-treated mice. These findings may be useful in comprehending the molecular action of GA on STAT3 phosphorylation and provide novel insights into the potential application of GA in the treatment of STAT3-related inflammatory disease, such as IBD.

• IMMUNE NETWORK
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• 제20권3호
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• pp.24.1-24.14
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• 2020

Eosinophils are terminally differentiated cytotoxic effector cells that have a role in parasitic infections and allergy by releasing their granule-derived cytotoxic proteins. However, an increasing number of recent observations indicate that eosinophils are not only associated with the pathogenesis of a wide range of diseases, but also contribute to the maintenance of homeostatic responses in previously underappreciated diverse tissues, such as the gastrointestinal (GI) tract and adipose tissue. In this review, we describe biological characteristics of eosinophils, as their developmental properties, permissive proliferation and survival, degranulation activity, and migration properties enable them to distribute to both homeostatic and inflamed tissues. We describe pathologic aspects of eosinophils with a role in asthma and in various GI diseases, including eosinophilic GI disorders, inflammatory bowel disease, and radiation-induced enteropathy. Finally, we discuss the beneficial role of eosinophils, which contribute to the resolution of pathogenic conditions and to the modulation of homeostatic biologic responses.

• IMMUNE NETWORK
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• 제14권2호
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• pp.67-72
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• 2014

The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2-4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa.

• Journal of Microbiology and Biotechnology
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• 제33권8호
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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.

• Journal of Yeungnam Medical Science
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• 제38권1호
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• pp.70-73
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• 2021

Relapsing polychondritis (RP) is a rare, progressive immune-mediated systemic inflammatory disease of unknown etiology, characterized by recurrent inflammation of cartilaginous structures. Approximately 30% of RP cases are associated with other autoimmune diseases. However, the co-occurrence of RP and Crohn disease (CD) has rarely been reported. Herein, we present a 35-year-old woman diagnosed with RP and CD, who was refractory to initial conventional medications, including azathioprine and glucocorticoid, but who subsequently responded to infliximab (IFX). For both diseases, remission was sustained with IFX. There has been no previous report regarding the successful treatment of co-existing RP and CD with IFX.

• Molecules and Cells
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• 제38권11호
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• pp.1013-1021
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• 2015

Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immune-modulating drug that is used in rheumatology and inflammatory bowel disease. Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS.

• 대한약침학회지
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• 제27권2호
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• pp.59-69
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• 2024

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

• 한국식생활문화학회지
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• 제39권1호
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• pp.74-81
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• 2024

Ulcerative colitis (UC) is a chronic inflammatory intestinal disease characterized by an imbalance in immune function and the overexpression of inflammatory cytokines and mediators. Vitamin B2, also known as riboflavin (Libof), is an essential water-soluble vitamin with numerous beneficial properties, including antioxidant, anti-aging, anti-inflammatory, anti-nociceptive, and anti-cancer effects. In this study, we aimed to investigate the protective effects of Libof on dextran sulfate sodium (DSS)-induced experimental colitis. The C57BL/6 mice were used as the in vivo model of chronic colitis to investigate the anti-inflammatory effects of Libof. RAW 264.7 cells were used for the in vitro investigation of the molecular mechanisms underlying these effects. In vivo, Libof alleviated the DSS-induced disease activity index (DAI), colon length shortening, and colonic pathological damage. In vitro, Libof inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production in RAW 264.7 cells. Moreover, Libof inhibited LPS-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. In conclusion, these findings indicate that Libof shows potential as an agent for the treatment of UC.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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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.

• Journal of Digestive Cancer Research
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• 제10권1호
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• pp.31-38
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• 2022

Ulcerative colitis (UC) exhibits chronic intestinal inflammatory conditions with cycles of relapse and remission. The incidence is rapidly growing in Asian countries including South Korea possibly due to changes in lifestyles. Although the etiology of inflammatory bowel disease is inconclusive, gut microbiota composition is considered a critical factor involved in the pathogenesis of UC. The overgrowth of pathogenic bacteria evokes hyper-immune responses in gut epithelium causing tissue inflammation and damage. Also, failure to regulate gut epithelium integrity due to chronic inflammation and mucus depletion accelerates bacterial translocation aggravating immune dysregulation. Gut microbiota composition responds to the diet in a very rapid manner. Epidemiological studies have indicated that the risk of UC is associated with low plant foods/high animal foods consumption. Several bacterial strains consistently found depleted in UC patients use plant food-originated dietary fiber producing short chain fatty acids to maintain epithelial integrity. These bacteria also use mucus layer mucin to keep gut microbiota diversity. These studies partly explain the association between dietary modification of gut microbiota in UC development. Further human intervention trials are required to allow the use of specific bacterial strains in the management of UC.