• Korean Journal of Acupuncture
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• 제25권2호
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• pp.159-177
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• 2008

Objectives : Crohn's disease is a severe chronic inflammation that is treated mainly by immunosuppression, which often has serious side effects. There is need to develop new therapeutic methods or drugs that have few side effects in order to treat this disease. Acupuncture with Moxi-tar at Cheonchu (ST25) has anti-inflammatory properties, but the mechanism of its anti-inflammatory actions is unclear. We investigated the protective effects and speculated the mechanisms of acupuncture with Moxi-tar at ST25 on trinitrobenzene sulfonic acid (TNBS) induced colitis in mice which is a well known Crohn's disease animal model. Methods : 5 % TNBS was treated at day 1 and day 7 into rectum of mice. To investigate therapeutic effects of acupuncture with Moxi-tar at ST25, acupuncture was carried out on day 3, and day 6. For the data analysis, we observed macroscopic and microscopic findings of the colon. Weight and width of the colon, degree of damage, changes of body weight, and myeloperoxygenase (MPO) activity were checked. For analysing protein expression, we carried out immunohistochemical staining and Western blot. For analysing mRNA expression, RT-PCR was carried out. Results : TNBS induced damages on the colon of mice, while acupuncture of Moxi-tar at ST25 suppressed TNBS mediated damages similar to those on the colons of mice in the control (not treated with TNBS) group. The average body weight of TNBS treated mice (77.4%) was decreased compared with that of the control mice (105%), and acupuncture with Moxi-tar at ST25 suppressed the loss of body weight caused by TNBS (from 77.4% to 95.3%). TNBS induced infiltration of immune cells in all layers of the colon while acupuncture with Moxi-tar at ST25 suppressed infiltration of immune cells caused by TNBS. Furthermore, acupunctured with Moxi-tar at ST25 suppressed macro-, micro- colonic damages caused by TNBS. Acupunctured with Moxi-tar at ST25 dramatically improved the clinical and histopathological symptoms such as the increase in weight of the distal colon and the MPO activity in TNBS-induced colitis. Acupuncture with Moxi-tar at ST25 down-regulated the nuclear transcription factor kappa B ($NF-{\kappa}B$) activity and suppressed tumor necrosis factor-a (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-1${\beta}$), and intracellular adhesion molecule-1 (ICAM-1) expressions caused by TNBS. Conclusions : Acupuncture with Moxi-tar at ST25 helps recovery from the TNBS-induced colonic damage by down-regulation of $NF-{\kappa}B$ activity and suppressing of TNF-${\alpha}$, IL-1${\beta}$, and ICAM-1 expressions. This may be an important method for the treatment of Crohn's disease.

• 대한수의학회지
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• 제47권1호
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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.

• Korean Journal of Acupuncture
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• 제21권2호
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• pp.95-110
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• 2004

Objectives : Ulcerative colitis and Crohn's diseases are chronic inflammatory disease of the gastrointestinal tract identified mainly for diarrhea, stomachache, hemafecia. The source and pathologic mechanism about ulcerative colitis and Crohn's disease are still unknown but stress, infection, a genetic factor, environmental factors etc. may be the cause of chronic inflammatory disease of the gastrointestinal tract recently. Methods : Because ulcerative colitis and Crohn's disease is recognized as Ha-ri(下痢) or Jang-Byok(腸?) in Oriental Medicine, Rhizoma Coptidis Herbal acupunctures were injected in hapgok $(LI_4)$ which is used to treat intestinal disease in clinic. All animals were subjected to the injection of saline $(300\;{\mu}l,\;500\;{\mu}l)$ for a study control and TNBS $(300\;{\mu}l,\;500\;{\mu}l)$ into the lumen of the colon, 8cm proximal to the anus through the intestine. Rhizoma Coptidis Herbal (20 mg/ml, 0.4 ml) acupuncture solution was injected to the $LI_4$ (both hands) at the secondary injection time of TNBS in rats. And body weight, RBC count, WBC count, total protein, Paw edema rate, rate of protein leakage into CMC-pouch fluid, IgG levels and IgM levels were observed to study the effects of Rhizoma Coptidis Herbal acupuncture in hapgok $(LI_4)$. Results : In results, Rhizoma Coptidis Herbal acupuncture in hapgok $(LI_4)$ on TNBS-induced colitis reduced the rate of weight loss but had no effect on RBC and WBC count. And it reduced total protein concentration, paw edema, rate of protein leakage into CMC-pouch fluid, IgG levels and IgM levels. Conclusion : Data suggest that injection of Rhizoma Coptidis herbal acupuncture solution into hapgok has significant therapeutic effect on the colitis.

• Korean Journal of Acupuncture
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• 제24권3호
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• pp.149-164
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• 2007

Objectives : Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease in the gastrointestinal tract. The sources and pathologic mechanisms of IBD are still unknown. Moreover conventional therapies for IBD are not always effective, and they often have serious side effects. The purpose of this study is to examine the effect of Moxi-tar herbal acupuncture in IBD affected mice. Methods : Mice were treated with 5 % 2, 4, 6 - trinitrobenzenesulfonic acid (TNBS) on day 1 and day 7. To assume the preemptive effect and therapeutic effect, herbal acupuncture was practiced with Moxi-tar at BL25 (Daejangsu) on day 0, day 3, and day 6. The end of day in treatment with Moxi-tar herbal acupuncture, the mortality and the inflammatory factors of the colon were measured by the various methods. Results TNBS induced high mortality but herbal acupuncture with Moxi-tar at BL25 sup-pressed the mortality caused by TNBS. TNBS induced infiltration of immune cells in all layers of the colon and increased myeloperoxygenase (MPO) activity, while the treatment with Moxi-tar herbal acupuncture at BL25 suppressed the infiltration of immune cells and the increase of MPO activity caused by TNBS to normal levels, Herbal acupuncture with Moxi-tar regulated $NF-{\kappa}B$ activity, which is an important factor for the pathogenesis of chronic colitis, and reduced the expressions of $TNF-{\alpha}$, $IL-1{\beta}$, and ICAM-1 in the colons of TNBS treated mice. Furthermore herbal acupuncture suppressed macro- and micro- colonic damages caused by TNBS. Conclusions : This study demonstrates that herbal acupuncture with Moxi-tar at BL25 isa potential preemptive and/or therapeutic method targeting the chronic IBD.

• 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.

• Journal of Microbiology and Biotechnology
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• 제19권6호
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• pp.616-621
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• 2009

To evaluate the effects of lactic acid bacteria (LAB) in inflammatory bowel diseases (IBD), we measured the inhibitory effect of several LAB isolated from intestinal microflora and commercial probiotics against the glycosaminoglycan (GAG) degradation by intestinal bacteria. Bifidobacterium longum HY8004 and Lactobacillus plantarum AK8-4 exhibited the most potent inhibition. These LAB inhibited colon shortening and myeloperoxidase production in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitic mice. These LAB also blocked the expression of the proinflammatory cytokines, IL-$1{\beta}$ and TNF-$\alpha$, as well as of COX-2, in the colon. LAB also blocked activation of the transcription factor, NF-${\kappa}B$, and expression of TLR-4 induced by TNBS. In addition, LAB reduced the TNBS-induced bacterial degradation activities of chondroitin sulfate and hyaluronic acid. These findings suggest that GAG degradation-inhibitory LAB may improve colitis by inhibiting inflammatory cytokine expression via TLR-4-linked NF-${\kappa}B$ activation and by inhibiting intestinal bacterial GAG degradation.

• 대한한방내과학회지
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• 제31권2호
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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.

• 한국임상수의학회지
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• 제20권1호
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• pp.22-25
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• 2003

본 연구는 정상 및 결장염을 유발한 rat에서 침술이 결장운동성에 미치는 영향을 알아보고, 이에 내인성 opioid가 관여하는지의 여부를 알아보기 위하여 수행하였다. 22마리의 Sprague-Dawley rat을 정상군 (n=8), 결장염군 (n=6) 및 maloxone군(n=8)의 세군으로 나누어 실험을 실시하였다. Rat의 근위 결장의 장막하에 스테인레스 전극을 장착하고, 전극장착 7일 후에 trinitrobenzene sulphonic acid(TNBS)과 ethanol을 이용하여 결장염을 유발하였다. 결장의 근전도는 전극장착 11일 후에 trinitrobenzene sulphonic acid(TNBS)과 ethanol을 이용하여 결장염을 유발하였다. 결장의 근전도는 전극장착 11일 후에 polygraph를 이용하여 측정하였다. 정상군에서는 정상 결장의 기초 근전도를 60분간 기록한 후에 GV-1에 20분간 전통 침술을 실시하고, 다시 60분간 근전도를 가록하였으며, 결장염군에서는 TNBS/ethanol이 미리 투여된 rat에 정상군에서와 같은 방법으로 근전도 기록 및 침술을 실시하였다. Naloxone 군에서는 결장염군과 같은 방법으로 TNBS/ethanol이 미리 투여된 rat에 침술을 실시하기전 naloxone(3 mg/kg, SC)을 투여하고 다른 군에서와 마찬가지로 근전도와 침술을 실시하였다. 정상군에서는 침술이 결장의 운동성에 영향을 미치지 않았다. 그러나 TNBS/ethanol을 투여하여 결장염이 유발된 결장염군에서는 침술에 의해서 결장의 운동성이 유의적으로 저하되었다(p＜0.01). Naloxone군에서는 침술에 의한 결장운동성의 저하는 관찰할 수 없었다. 이상의 결과로 보아 rat에서 GV-1 혈위의 침술에 의해 유발된 내인성 opioid는 염증상태의 결장 운동성을 감소시킨 것으로 사료된다.

• 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.

• 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.