• Journal of Applied Biological Chemistry
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• 제60권3호
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• pp.227-234
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• 2017

염증성 장 질환에 일반적으로 사용되는 설파살라진은 고용량 및 장기 섭취 후 다양한 부작용이 있다. 본 연구에서는 TNBS로 유발된 마우스 대장염 모델에서 설파살라진, 육계와 시호 복합 추출물의 항염증 및 세포 자멸 개선효과를 확인하고자 하였다. 실험은 정상군, TNBS 대조군, Sulfasalazine (30 mg/kg)군, Sulfasalazine (60 mg/kg)군, Sulfasalazine (30 mg/kg)+육계 및 시호 혼합 (30 mg/kg)군, 총 5개의 군으로 나누었으며, 7일간 경구투여 하였다. 염증 및 세포 자멸 단백질은 western blot을 통해 발현량을 확인하였다. SCB 투여는 염증 단백질 및 세포 자멸과 관련된 단백질의 억제에 유의한 효과를 나타냈다. 이러한 결과로 보아 설파살라진, 육계와 시호 복합 추출물은 염증과 세포 자멸의 억제를 통해 염증성 장 질환을 개선시킬 수 있으며, 염증성 장 질환의 치료 대안 가능 물질로 사료되는 바이다.

• IMMUNE NETWORK
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• 제15권3호
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• pp.135-141
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• 2015

Dysfunction of gut immune regulation is involved in mucosal damage in inflammatory bowel disease (IBD). However, there is still no efficacious immune-regulator for the treatment of IBD. Alloferon is a novel immune-modulatory peptide that was originally isolated from infected insects. It shows anti-inflammatory effects by the regulation of cytokine production by immune cells and their activities. Therefore, we investigated the effect of alloferon in a mouse model of colitis using dextran sulfate sodium (DSS). Colitis was induced by administration of DSS in drinking water for 7 consecutive days. It was confirmed by the presence of weight loss, diarrhea, hematochezia, and colon contraction. Alloferon was injected 4 days after DSS administration. We found that alloferon improved the pathogenesis of IBD based on the reduced disease activity index (DAI) and colon contraction. Edema, epithelial erosion, and immune cell infiltration were found in mice administered DSS, but the phenomena were reduced following alloferon treatment. The plasma level of IL-6, a classical pro-inflammatory cytokine in colitis, was also decreased by alloferon. Moreover, alloferon inhibited the TNF-${\alpha}$-induced degradation and phosphorylation of $I{\kappa}B$ in Colo205 colon cancer cells. Taken together, these results show that alloferon has anti-inflammatory effects and attenuates DSS-induced colitis.

• 한국산학기술학회논문지
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• 제10권3호
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• pp.613-619
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• 2009

SHI-1909를 초산과 TNBS에 의해 rat에 유발된 염증성 대장염 모델에서 5일 동안 경구 투여 하여 대조약인 프레드니솔론과 그 치료 효능을 비교 조사하였다. 7% 초산과 5% TNBS 용액을 polyethylene 튜브로 rat의 항문에 점적하여 염증성 대장염을 유발하였으며 점적 후 초산과 TNBS 대조군은 말단의 대장부위에서 궤양과 염증 증상 같은 병적인 소견을 보여 염증성 대장염이 잘 유발되었음을 확인할 수 있었다. 약물의 투약기간 중 염증 치유 변수인 실험동물의 중량과 식이 섭취량 변화를 관찰하였으며 실험이 종료된 후에는 실험동물을 희생시킨 후 대장의 길이와 궤양, 병적인 소견을 조사하였다. SHI-1909의 투여는 중량변화와 식이 섭취량 등에서 대조약과 필적할 만한 결과를 나타내었으며 특히 대장의 손상 정도 평가에서 대조약물인 프레드니솔론보다도 더 우수한 효과를 나타내었다. 이러한 결과로부터 SHI-1909는 IBD의 치료에 가능성이 있는 치료 약물이 될 수 있을 것으로 사료된다.

• IMMUNE NETWORK
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• 제11권6호
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• pp.416-419
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• 2011

Dextran sodium sulfate (DSS) is a widely used chemical model for inflammatory bowel disease (IBD). It is thought that imbalances in the T helper (Th) cell subsets contribute to IBD. Recent studies suggest that the acute DSS-colitis model is polarized toward a Th1/Th17 profile based on RT-PCR analysis of colonic tissues. In the current study we determined whether colonic Th cells from DSS-colitis mice were skewed toward the Th17 profile. Mice were treated with 5% DSS for 7 days and colonic T cells isolated and examined for production of IFN-${\gamma}$ (Th1 cell), IL-4 (Th2 cell) and IL-17 (Th17 cell) by intracellular flow cytometry. We found that the percentage of colonic Th17 cells were similar to non-treated controls but the percentage of Th1 cells were elevated in DSS-colitis mice. These results suggest that in the acute DSS-colitis model the colonic Th cells exhibit a Th1 profile and not a Th17 profile.

• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2009년도 추계학술발표논문집
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• pp.318-321
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• 2009

The Efficacy of PSB-2061, was investigated in comparision with predinisolone in acetic acid and Picrylsulfonic acid solution (TNBS)-induced rat inflammatory bowel disease (IBD) for 5 days. 5 % TNBS solution were administered with polyethylene (P.E) tube inserted to rats intracolon, which causing colitis to the rats. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. We checked the inflammatory parameters like rat's weight, food intake quantity change during administration. After 5 days, we sacrificed the rats and checked the colon's length, ulcer and pathologic condition. Oral treatment with PSB-2061 resulted in significant recovery of macroscopic parameters like weight and diet intake change. Especially, PSB-2061 extract had a more potent effect than $mesalazine^{(R)}$ on macroscopic colonic damage score. We can suggest that PSB extract could be a promising drug in the treatment of IBD.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.536-544
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• 2021

5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.

• 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.

• Clinical Endoscopy
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• 제57권3호
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• pp.317-328
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• 2024

Background/Aims: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD). Methods: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I²% was used to assess heterogeneity. Results: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc resection, R0 resection, and curative resection rates were 92.5% (95% confidence interval [CI], 87.9%-95.4%; I²=0%), 81.5% (95% CI, 72.5%-88%; I²=43%), and 48.9% (95% CI, 32.1%-65.9%; I²=87%), respectively. The local recurrence rate was 3.9% (95% CI, 2%-7.5%; I²=0%). The pooled rates of bleeding and perforation were 7.7% (95% CI, 4.5%-13%; I²=10%) and 5.3% (95% CI, 3.1%-8.9%; I²=0%), respectively. The rates of metachronous recurrence and additional surgery following ESD were 10% (95% CI, 5.2%-18.2%; I²=55%) and 13% (95% CI, 8.5%-19.3%; I²=54%), respectively. Conclusions: ESD is safe and effective for the resection of dysplastic lesions in IBD with an excellent pooled rate of en-bloc and R0 resection.

• 한국축산식품학회지
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• 제32권2호
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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.

• Journal of Ginseng Research
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• 제47권5호
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.