• 대한한방내과학회지
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• 제34권2호
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• pp.134-146
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• 2013

Objectives : Auklandia Lappa (ALE) is one of the herbs used frequently to treat abdominal pain and diarrhea and reported anti-inflammatory activity by suppressing proinflammatory cytokines. This study was designed to investigate whether ALE could show protective activities on experimental colitis induced by dextran sulfate sodium (DSS) models. Methods : Colitis was induced by DSS in Balb/c mice. ALE 10, 30, 100 and 300 mg/kg were orally administered twice a day for 7 days in DSS model. Mice weight was measured daily. Scoring of clinical findings was measured every other day. Colon length, edema, fecal blood and histological damages were assessed at day 7 in DSS model. In histological analysis, we checked cryptal glands, surface epithelium, submucosa, transmural, stroma and scored degree of inflammatory cell damage by modified histological scoring. We also calculated cytokines concentrations including IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, IL-17, IL-23, IL-10 and TGF-${\beta}1$ by Biometric Multiplex Cytokine Profiling method. Results : ALE showed the protective effects on DSS-induced experimental colitis. ALE inhibited shortening of colon length and histological damages of colon does-dependently, but it did not inhibit weight loss. ALE also inhibited IFN-${\gamma}$ and IL-6 expression, and upregulated cytokines (IL-10, TGF-${\beta}1$) related to regulatory T cell differentiation and proliferation. Conclusions : The current results demonstrate the clinical utility of ALE in traditional medicine and indicate the possibility of potent drug development of inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.

• 동의생리병리학회지
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• 제26권5호
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• pp.672-678
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• 2012

Colitis and constipation are the most common intestinal complaints worldwide. This study examined the beneficial effects of sea cucumber powder for TNBS-induced colitis in ICR mice(n=6/group) and loperamide-induced constipation in rats(n=8/group). Animals were divided into normal and four dried see cucumber treated groups that were named Nor, Con(0 mg/kg), GI(30 mg/kg), GII(100 mg/kg) and GIII(300 mg/kg). In order to induce colitis and constipation, 5% TNBS was injected into distal colon and loperamide (2 mg/kg, twice a day, peroral) was treated for 5 day in the four experimental groups but not the normal group. Gross finding score was decreased tendency by oral administration of sea cucumber in colitis-induced animal model, but colonic weight was not different. Excreted fecal pellet number, weight and water content were increased in the sea cucumber-treated group compared to the non-treated group. The fecal pellet number was reduced within distal colon of the sea cucumber-treated groups. Interestingly, intestinal transit length was increased compared to the non-treated group. Our results demonstrated that colitis and constipation were improved by sea cucumber treatment in the animal models. Specifically, gross finding score in TNBS-induced colitis model was improved by sea cucumber. After animals being fed sea cucumber, excreted fecal number, weight, water contents, and fecal number within distal colon and colonic transit length also get better in loperamide-induced constipation model.

• 대한한방내과학회지
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• 제29권2호
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• pp.385-400
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• 2008

Objectives : This study was carried out to investigate the effects of Soyumjungjang-tang(SJT) on the experimental ulcerative colitis induced by dextran sulfate sodium(DSS) in mice. Methods : Ulcerative colitis was induced through supplying 4% DSS solution as the drinking water for 7 days in 6-week-old male ICR mice. The colitic mice were divided into three groups: the sample groups were orally administered SJT in doses of 25mg/kg(S25 group) or 100mg/kg(S100 group) once a day for 10 days, from 3 days before starting drinking the DSS solution, and the control(C) group was administered normal saline instead of SJT. The DSS solution or SJT was not administered to the normal(N) group. The length of colon, histologic finding, the activities of myeloperoxidase(MPO) and alkaline phosphatase(AP), and the expressions of $IL-1{\beta}$, IL-6, COX-2, $NF-{\kappa}B$, and $I{\kappa}B$ in colonic mucosa was checked using immunoblot, ELISA, etc. The activities of chondroitinase, tryptophanase, ${\beta}-glucuronidase$ and ${\beta}-glucosidase$ in stool were also measured. Results : The length of colon shortened, histologic finding deteriorated, the activities of MPO, AP, chondroitinase, tryptophanase, ${\beta}-glucuronidase$ and ${\beta}-glucosidase$, and the expressions of $IL-1{\beta}$, IL-6, COX-2, $NF-{\kappa}B$ increased, and the expression of $I{\kappa}B$ decreased in the C group. All measures, except $NF-{\kappa}B$, were restored in S25 group, but some measures deteriorated more in the S100 group than in the C group. Conclusions : According to the above results, it is supposed that SJT has a potential therapeutic effect on ulcerative colitis.

• Journal of Acupuncture Research
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• 제35권1호
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• pp.11-20
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• 2018

Background: This research was performed to investigate the effects of Pulsatilla Koreana NAKAI pharmacopuncture (PPA) therapy on intestinal disease in rats with dextran sulfate sodium (DSS)-induced colitis. Methods: The subjects were divided into five groups : A control group, saline group, pharmacopuncture group PPA1 ($0.2mg/1kg/40{\mu}{\ell}$), pharmacopuncture group PPA2 ($0.5mg/1kg/40{\mu}{\ell}$), and pharmacopuncture group PPA 3($1mg/1kg/40{\mu}{\ell}$). The experimental model of colitis was induced by infection of dextran sulfate sodium (DSS) for eighteen days. After colitis was induced, PPA therapy was practiced on the Chunchu (ST25) once every two days for a total six times. Thereafter Disease Activity Index (DAI), colon length, damage to the colonic mucosa, body weight, IL-6, IL-10, $IL-1{\beta}$, $IFN-{\gamma}$, $TNF-{\alpha}$, $TGF-{\beta}1$, IL-23 and IL-17 were measured. Results: The results were as follows. 1. DAI was significantly decreased in the PPA groups. 2. Colon length was significantly increased in the PPA groups. 3. Damage of colonic mucosa was observed less in the PPA groups. 4. Body weight was significantly increased in the saline group and the PPA groups. 5. The PPA2 group showed a significant decrease in the intensity of IL-6, $IL-1{\beta}$, $IFN-{\gamma}$ and $TNF-{\alpha}$ levels and the mean of IL-23. 6. The PPA3 group showed a significant increase in the intensity of IL-10 and $TGF-{\beta}1$ levels. 7. No significant differences were shown in the mean of IL-17. Conclusion: These results suggest that PPA therapy on Chunchu (ST25) can be used as an effective treatment for inflammatory bowel disease.

• Parasites, Hosts and Diseases
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• 제50권4호
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• pp.385-390
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• 2012

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of $CD4^+CD25^+Foxp3^+$ T (regulatory T; $T_{reg}$) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-${\gamma}$, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-${\beta}$, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of $T_{reg}$ cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and $T_{reg}$ cells recruitment.

• 한국식품영양학회지
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• 제34권2호
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• pp.146-155
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• 2021

This study observed the anti-inflammatory effect of the polysaccharide derived from the mycelium of Tremella fuciformis in mice with colitis induced with dextran sulfate sodium (DSS). The experimental groups were normal, DSS, DSS-TFL50, DSS-TFH100, and suflasalazine. Body weights, colon lengths, and organ weights were measured, and the plasma level of pro-inflammatory cytokine and mRNA and protein expression in colon tissue were analyzed. Body weight loss, a symptom of DSS-induced colitis, was suppressed by DSS-TF and the speed of weight recovery proceeded rapidly. In addition, DSS-TF showed a significant inhibitory effect on the decrease of colon length typically caused by colon damage. TNF-α, IL-6 and IL-1β cytokine levels in plasma were reduced in DSS-TF and positive control groups. TNF-α, COX-2 and IL-1β mRNA expression in colon tissue were inhibited in DSS-TF and positive control, and it was significantly different from that of the DSS group. The protein expression of inflammation-related genes (IL-6, TNF-α and COX-2) in the colon tissue was significantly increased by DSS compared to that of the normal group, but by DSS-TFL50, DSS-TFH100 and sulfasalarin decreased. In conclusion, the polysaccharide derived from the mycelium of Tremella fuciformis showed the anti-inflammatory effect on DSS-induced colitis in mice.

• International Journal of Internet, Broadcasting and Communication
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• 제13권2호
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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.

• 대한한의학방제학회지
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• 제31권4호
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• pp.341-360
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• 2023

Background : To investigate the effect of Hwanggeumjackyak-tang (HJT) on Dextran sulfate sodium (DSS) induced ulcerative colitis. Methods : The experimental animals were divided into three groups; group 1, normal group(Normal); group 2, DSS-induced colitis and untreated group(UT+DSS); group 3, DSS-induced colitis and HJT 200 mg-treated group(HJT200+DSS). We evaluated cytotoxicity after HJT administration and confirmed the anti-inflammatory effect by histological changes in the intestine and genetic analysis of mucosal cells after HJT administration for each group. In addition, microbiological weapons and metabolites in faeces were examined, and the correlation between gut microbiome and metabolites was also investigated. Result : HJT was not observed to be cytotoxic, even at relatively high concentrations, and was effective in protecting the barrier and preventing intestinal inflammation by suppressing the increase in mucus secretion and the expression of inflammatory factors in mucosal cells. HJT treatment affected the increase in the amount and diversity of the gut microbiome in faeces and the increase in metabolites thought to be involved in alleviating inflammation in the gut. Conclusion : This study demonstrates the therapeutic potential of HJT in ulcerative colitis. Further studies should be carried out to confirm our findings.

• The Korean Journal of Physiology and Pharmacology
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• 제19권1호
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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.

• 생명과학회지
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• 제29권9호
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• pp.941-948
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• 2019

Ziyuglycoside-II ($3{\beta}-3-{\alpha}$-1-arabinopyranosyloxy-19-hydroxyurs-12-en-28-oicacid)는 오이풀(Sanguisorba officinalis L.)의 주요 활성 화합물 중 하나로 지혈작용, 항산화활성, 항염증활성 등의 활성이 보고되어 있다. 그러나 염증성 대장암에서의 ziyuglycoside-II의 활성에 관해서는 아직 보고되지 않아 본 연구에서 azoxymethane (AOM)/dextran sulfate sodium (DSS)으로 유발된 대장암 모델에서 ziyuglycoside-II 항종양활성을 조사하였다. 염증성 대장암을 유발하기 위해 BALB/c 마우스에게 AOM을 1회 복강 주사하고 AOM 투여 1주일 후 총 3 cycle의 2% 농도의 DSS를 음용수로 공급 하였다. Ziyuglycoside-II (1 또는 5 mg/kg)는 1주일에 3회 경구 투여하고, 64일에 대장을 적출하였다. 대장 조직에서의 종양 개수를 관찰한 결과 ziyuglycoside-II의 투여가 종양의 형성을 유의적으로 감소시키는 것을 확인하였다. 또한 Western blot 방법과 면역 조직학 분석의 결과, ziyuglycoside-II의 투여가 대장 조직에서 nuclear factor kappa-B 양성 세포와 염증 관련 단백질의 양을 현저히 감소시킴을 관찰하였다. 또한 ziyuglycoside-II 투여에 의해 대장조직내의 세포사멸이 촉진되었고 cleaved-caspase 3, cleaved-caspase 7과 같은 세포사멸 관련 단백질의 발현이 증가함을 확인하였다. 이러한 결과는 ziyuglycoside-II의 투여가 염증반응을 억제하고 세포 자멸을 유도하여 염증성대장암의 발생을 억제함을 시사하고 있다.