• Korean Journal of Acupuncture
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• v.25 no.2
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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.

• Korean Journal of Acupuncture
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• v.21 no.2
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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.

• Journal of Veterinary Clinics
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• v.20 no.1
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• pp.22-25
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• 2003

The aims of this study were to investigate the efficacy of acupuncture on myoelectrical activity of inflamed or normal colon in the rat, and whether the effect of acupuncture on colonic motility was related to endogenous opioids. Twenty-two male Sprague-Dawley rats were divided into three groups. Experimental groups were normal group (n = 8), colitis group (n = 6) and naloxone group (n = 8). Stainless steel bipolar electrodes were implanted on the serosal layer of the proximal colon of rats. Colitis was induced 7 days after electrode implantation using trinitrobenzene sulphonic acid (TNBS) and ethanol. Electromyograms (EMG) were recorded by using polygraph 11 days after implantation of electrodes. In normal group, normal colonic motility was recorded for 60 min, and then traditional acupuncture at GV-1 was applied for 20 min and EMG was recorded for further 60 min in untreated rats. In colitis group, after recording of basal colonic motility for 60 min, 20 min of acupuncture treatment and further EMG recording was performed for 60 min in TNBS/ethanol treated rats. In naloxone group, following subcutaneous administration of naloxone (3 mg/kg), recording of EMG and acupuncture treatment were performed in TNBS/ethanol treated rats. In the normal group, acupuncture at GV-1 did not induce significant changes in colonic motility. TNBS/ethanol treatment had no significant effect on the frequency of colonic motility. And in colitis group, GV-1 acupuncture significantly decreased colonic motility (p < 0.01). In naloxone group, after injection of naloxone, acupuncture at GV-1 did not change colonic motility in TNBS/ethanol treated rats. On the inflamed colon, naloxone blocked the effect of acupuncture. The present results suggested that endogenous opioids released by acupuncture at GV-1 decrease the motility of inflamed colon in rats, but not normal colon.

• Korean Journal of Veterinary Research
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• v.47 no.1
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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.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.3
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• pp.613-619
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• 2009

The Efficacy of SHI-1909 was investigated in comparision with predinisolone in acetic acid and Picrylsulfonic acid solution (TNBS)-induced rat inflammatory bowel disease (IBD) for 5 days. 7% Acetic acid and 5% TNBS solution were administered with polyethylene (P.E) tube inserted to rats intracolon, which causing colitis to the rats. The acetic acid and 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 SHI-1909 resulted in significant recovery of macroscopic parameters like weight and diet intake change. Especially, SHI-1909 had a more potent effect than prednisolone on macroscopic colonic damage score. We can suggest that SHI-1909 could be a promising drug in the treatment of IBD.

• Korean Journal of Acupuncture
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• v.24 no.3
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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.

• Proceedings of the KAIS Fall Conference
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• 2009.12a
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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.

• Journal of Applied Biological Chemistry
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• v.60 no.3
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• pp.227-234
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• 2017

Inflammatory bowel disease (IBD) is including Crohn's disease and ulcerative colitis. Sulfasalazine commonly used in IBD, possibly has various side effects after high dosage and long term intake. The present study aimed to investigate the sulfasalazine and combination with herbal medicine on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced in mice model. TNBS-induced mice were injected through a flexible catheter 4 cm in length 1.6 mg TNBS. Animals were divided into five groups (n=12): Normal group, TNBS control group, Sulfasalazine (30 mg/kg) group, Sulfasalazine (60 mg/kg) group, Sulfasalazine (30 mg/kg)+Cinnamomi cortex and Bupleuri radix mixture (30 mg/kg) (SCB) group. Administration groups were fed extract during 7 days. The inflammatory, and apoptotic protein levels were determined using western blotting. SCB treatment showed an outstanding effectiveness in counteracting the IBD, as assessed by reduction of body weight loss, down-regulation of pro-inflammatory proteins and cytokines, and by inhibition of proteins related to apoptosis. This is the first report that sulfasalazine and Cinnamomi cortex plus Bupleuri radix mixture improve the severity of experimental IBD through the inhibition of both inflammation and apoptosis. We confirm that the SCB treatment instead of sulfasalazine alone may be promising as an alternative therapeutic plan against IBD, without any evidence of adverse effects.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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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.

• Journal of Applied Biological Chemistry
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• v.54 no.1
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• pp.51-55
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• 2011

To develop a health-aid preparation of Dioscorea batatas (DB), lactic acid fermentation was attempted using a mixed starter comprising of Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium longum. The anaerobic fermentation of a 10% DB flour suspension gave a uniform suspension of pH 3.65, containing $8{\times}10^6$ CFU/mL lactic acid bacteria. During the administration of the lactic acid fermented DB (FDB) and DB to trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model, histological lesions, morphological damage, and myeloperoxidase acitivity were significantly reduced at a dosage of 200 and 400 mg/kg/day. Dose-response (200 and 400 mg/kg/day) studies revealed that FDB pre-treatment of mice significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. In FDB-pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and weight loss rates. Theses findings suggest that FDB exerts beneficial effects in experimental colitis and may be useful in the treatment of inflammatory bowel disease.