• 한국한의학연구원논문집
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• 제17권3호
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• pp.105-114
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• 2011

Objectives : The transient inflammation has been demonstrated to alter visceral motor response (VMR) and acute mucosal inflammation may precede the manifestation of visceral hyperalgesia in animal models. The purpose of our study is to compare effects of the different frequencies applied electroacupuncture (EA) on acupoints in acute colitis induced by trinitrobenzenesulphonic acid (TNBS). Methods : In Male Sprague-Dawley rats, weighing 250~400g, a single colorectal administration of TNBS (5mg/kg) was made and electrode for electromyography (EMG) recording were stitched into the external oblique musculature. EA of either ST25 or ST36 were applied and stimulation parameter was modulated as follows: 2, 10, or 100 Hz with intensity of 2 mA and 1 ms pulse duration for 30 min. The balloon was inserted intra-anally and VMR to colorectal distension (CRD) was quantified with an EMG recording system. Results : The VMR increased significantly 3 days after TNBS intra-rectal colonic injection in rats. Both 2 Hz and 10 Hz EA on ST36 suppressed VMR to CRD in the acute colitis model but not 100 Hz. Only 10 Hz EA on ST25 suppressed VMR to CRD in the acute colitis. Conclusions : These data show that 10 Hz EA potently inhibits hypersensitivity of colorectum after TNBS 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.

• 수산해양교육연구
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• 제12권2호
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• pp.213-223
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• 2000

액젓중의 아미태질소 함량의 정확한 측정방법을 확립하기 위하여, 아미노태질소 함량 측정방법으로 많이 사용되고 있는 포르몰법, TNBS법 그리고 동염법(銅鹽法)으로 까나리액젓의 숙성기간 및 시판액젓중의 아미노태질소 함량을 측정 비교하고, 액젓중의 아미노태질소 함량 측정시에 식염농도, 가열 및 MSG(monosodium glutamate) 첨가의 영향에 대하여 검토하였다. 까나리액젓의 숙성기간중의 아미노태질소 함량은 숙성기간에 따라서 일정하게 증가하였으며, 포르몰법이 가장 높았고 TNBS법 및 동염법(銅鹽法)의 순서였다. 12개월 숙성후의 아미노태질소 함량은 포르몰법을 기준으로 TNBS법은 88.7% 그리고 동염법(銅鹽法)은 75.2%였으며. 시판 까나리액젓중의 아미노태질소 함량도 포르몰법이 가장 높았고 TNBS법 및 동염법(銅鹽法)의 순서였다. 탈염 액젓중의 아미노태질소 함량은 포르몰법 및 TNBS법은 비슷한 값이었고, 동염법(銅鹽法)은 약간 낮았으며, 식염 첨가량이 많을 수록 포르몰법 및 동염법(銅鹽法)은 감소하였으나 TNBS법은 거의 일정하였다. 가열에 의한 영향은 거의 없었으며 포르몰법이 가장 높았고. TNBS법 및 동염법(銅鹽法)의 순서였다. MSG 첨가에 따른 아미노태질소 함량은 첨가농도에 비례하여 일정하게 증가하였으며, 숙성기간 및 가열중의 결과와 유사하게 포르몰법이 가장 많았고, TNBS법 및 동염법(銅鹽法)의 순서였다.

• 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.

• Korean Journal of Acupuncture
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• 제24권2호
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• pp.217-230
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• 2007

Objectives : Ulcerative colitis or Crohn's disease has been recognized as Ha-ri (下痢) or Jang-Byok in Korean oriental medicine. A purpose of the present study is to investigate the anti-inflammatory effect of moxi-tar herbal acupuncture at LI4 (HapGok) on 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis in rats and further elucidate the possibility of herbal acupuncture on ulcerative colitis which is chronic inflammatory disease of the gastrointestinal tract. Methods : Sprague-Dawley rats, weighing $170{\sim}190$ g, were subjected to intrarectal injection of either saline (300 ${\mu}l$, 500 ${\mu}l$) for a control or 2,4,6-trinitrobenzene sulphonic acid (TNBS) (300 ${\mu}l$, 500 ${\mu}l$) for a colitis, Moxi-tar (20 mg/ml) were subcutaneously injected to the LI4 just after the secondary injection time of TNBS in rats. To study the effects of Moxi-tar acupuncture in LI4, 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. Results: Moxi-tar acupuncture in LI4 on TNBS-induced colitis inhibited the body weight lose rate but not effect RBC, WBC count. In addition, it inhibited the reduction of total protein concentration, paw edema, rate of protein leakage into CMC-pouch fluid, IgG levels and IgM levels. Conclusions : It is suggested that moxi-tar herbal acupuncture at LI4 helps to recover TNBS-induced colitis and plays an important role for an treatment of the irritable bowel syndrome (IBS).

• Korean Journal of Acupuncture
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• 제26권4호
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• pp.195-209
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• 2009

Objectives : Transient inflammation has been demonstrated to alter visceral sensory function in animal models and acute mucosal inflammation may precede the manifestation of visceral hyperalgesia. Thus in this study we compared effects of herbal acupuncture of Nidus Vespae (NV) applied to the different acupoints in the acute colitis induced by trinitrobenzenesulphonic acid (TNBS) intracolonic injection in rats. Methods : In Male Sprague-Dawley rats, weighing 250 ~ 400 g, TNBS (5 mg/kg) was infused intrarectally through a silicon rubber catheter into the anus under isoflurane anaesthesia. Under general anesthesia, acupoints of LI4 (Hapkok), SI25 (Cheonchu), ST36 (Joksamni), BL25 (Daejangsu) were intramuscularly injected by NV. Expressions of cFos protein in the periaqueductal gray (PAG), locus coeruleus (LC), nucleus of solitary tract (Sol), and the 6th lumbar spinal cord (L6 s.c.) were observed at 24 hrs after TNBS induced colitis by immunohistochemistry. Results : The expression of c-Fos protein in L6 s.c., Sol, LC and PAG increased 24 hrs after TNBS injection into colorectum as compared to normal group. NV herbal acupuncture also inhibited the expression of c-Fos protein in Sol but not L6 s.c., LC, and PAG. NV to ST36 inhibited significantly the c-Fos expression in Sol and PAG. NV to ST25 inhibited the c-Fos protein expression all over the observation area. NV to BL25 showed the inhibitory effects in the areas except LC. Whether or not a role of endogenous opioids, intrathecal injection of naltrexone (30 ug / 30 ul) was applied before the 2nd herbal acupuncture treatment 24 hrs after TNBS-induced colitis in rat. Naltrexone reversed the inhibition of c-Fos protein expression in the spinal cord and brainstem under different conditions such as type of herbal acupuncture compound and choice of acupoint. Conclusions : In summary, these data show that herbal acupuncture of NV inhibits signal pathways such as spinal cord and brain stem ascending hypersensitivity of colorectum after TNBS induced colitis. This effect may be mediated by acupoints through the endogenous opioid system involving the pain modulation.

• Toxicological Research
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• 제20권4호
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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.

• 대한한방내과학회지
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• 제31권4호
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• pp.731-751
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• 2010

Objectives : The present study aimed to find out the effect of Sagunja-tang on the prevention and treatment of inflammatory bowel disease using mice with TNBS-induced inflammatory bowel disease. Methods : Mice with TNBS-induced inflammatory bowel disease were medicated with Sagunja-tang, and the weight changes, colon length, lipid peroxidation, and myeloperoxidase activity were observed. 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 were also measured. Finally, the activation of fecal bacterial enzyme, ${\beta}$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG) and hyaluronic acid were observed. Results : We found that oral administration of Sagunja-tang inhibited TNBS-induced colon shortening and also inhibited myeloperoxidase activity in the colon of mice as well as IL-$1{\beta}$ and COX-2 expression. Sagunja-tang also inhibited TNBSinduced lipid peroxidation and pp65 activation in the colon of mice. In addition, Sagunja-tang inhibited ${\beta}$-glucuronidase activation and fecal hyaluronic acid degradation activation. Conclusions : It is supposed that Sagunja-tang has a potential therapeutic effect on inflammatory bowel disease through the inhibition of both NF-${\kappa}$B activation and lipid peroxidation, and the improvement of intestinal conditions.

• IMMUNE NETWORK
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• 제6권1호
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• pp.13-19
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• 2006

Background: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti inflammatory way. Methods: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. Results: Re combinant human G-CSF significantly inhibited LPS-induced TNF-${\alpha}$ mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and intercellular adhesion molecule-1 in TNBS colitis. Conclusion: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

• Biomolecules & Therapeutics
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• 제20권5호
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• pp.457-462
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• 2012

The stem-bark of Kalopanax pictus (KP, family Araliaceae), of which main constituent is kalopanaxsaponin B, has been used for asthma, rhinitis, and arthritis in Chinese traditional medicine. To clarify anticolitic effect of KP, we examined anti-inflammatory effect of KP extract and kalopanaxsaponin B in lipopolysaccharide (LPS)-stimulated peritoneal macrophage and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. Of KP extracts, KP BuOH-soluble fraction most potently inhibited LPS-induced IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ expression, as well as NF-${\kappa}B$ activation. However, KP BuOH fraction increased IL-10, an anti-inflammatory cytokine. KP BuOH fraction also inhibited colon shortening and myeloperoxidase activity in TNBS-induced colitic mice. KP BuOH fraction also potently inhibited the expression of the pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ as well as the activation of NF-${\kappa}B$. Kalopanaxsaponin B, a main constituent of KP, inhibited TNBS-induced colonic inflammation, including colon shortening, and TNBS-increased myeloperoxidase activity pro-inflammatory cytokine expression and NF-${\kappa}B$ activation in mice. Based on these findings, KP, particularly its main constituent, kalopanaxsaponin B, may ameliorate colitis by inhibiting NF-${\kappa}B$ pathway.