• Journal of Life Science
• /
• v.33 no.10
• /
• pp.767-775
• /
• 2023

Sulfasalazine is a disease-modifying antirheumatic abiotic agent. It is a derivative of aminosalicylic acid and has been used for the treatment of various inflammatory diseases, such as rheumatoid arthritis, ulcerative colitis, and Crohn's disease, since it was first synthesized in 1941 and approved as a medicine in the United States in 1950. However, its mechanism of action has not yet been clearly identified. In this study, the effects of sulfasalazine on cell survival, apoptosis, and cell cycle progression in macrophages, which are major immune cells that regulate inflammatory responses, were investigated using mouse macrophage RAW 264.7 cells. Sulfasalazine inhibited the viability of RAW 264.7 cells in a dose-dependent manner, starting at a concentration of 0.25 mM. Annexin-V staining was used to confirm that the decrease in cell viability was due to apoptosis, and the number of Annexin-V-positive cells increased significantly at a concentration of 0.25 mM or higher. The effect of sulfasalazine on the expression of key proteins that regulate the G0/G1 phase of the cell cycle was also investigated. Sulfasalazine treatment significantly increased the expression of the cyclin-dependent kinase inhibitors p21 and p27 in RAW 264.7 cells. Although sulfasalazine is frequently used as a control drug in studies on inflammatory diseases, such as inflammatory colitis and rheumatoid arthritis, studies on its effect on macrophages are very limited. Therefore, the results of this study are expected to provide vital information on the use of sulfasalazine as a disease treatment.

• The Journal of Internal Korean Medicine
• /
• v.29 no.2
• /
• pp.385-400
• /
• 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.

• The Journal of Internal Korean Medicine
• /
• v.33 no.4
• /
• pp.520-532
• /
• 2012

Objectives : This study was carried out to investigate the effects of Coicis Semen Extract (CSE) on the experimental colitis induced by dextran sulfate sodium (DSS) in mice. Methods : Experimental colitis was induced by daily treatment with 5% DSS in the drinking water for 7 days in 6-week-old male ICR mice. The colitic mice were divided into three groups: the normal (N) group consisted of mice that were not inflammation-induced. The control (C) group was composed of untreated colitis elicited mice. The sample (S) group was administered CSE after colitis elicitation. The effects on colonic mucosal ulcers were evaluated by the morphological, histological and immunohistochemical change of the large intestine. Results : Inhibition of LPS-induced NO decreased in the S group. Inhibition of LPS-induced iNOS and COX-2 mRNA noticeably decreased in the S group from 0.25 mg/ml. In the common morphological and histochemical change, the erosion and the infiltration of inflammatory cells increased in the C group, while they noticeably decreased in the S group. The length of colon was shortened more in the C group than in the S group. The distributions of MUC2 and Hsp70 treated with CSE increased noticeably more in the S group than in the C group (p<0.05). It was confirmed histochemically and immunohistochemically that the distributions of iNOS, COX-2, MAC387, serotonin, apoptosis and PCNA treated with CSE decreased in the S group more than in the C group (p<0.05). Conclusions : It is confirmed that CSE has cytoprotective effect, so can alleviate inflammation process. Therefore, it is expected to have potential protective effect on colitis.

• The Journal of Pediatrics of Korean Medicine
• /
• v.32 no.3
• /
• pp.16-25
• /
• 2018

Objectives The purpose of this study is to investigate the anti-inflammatory effect of Lonicera Japonica-Glycyrrhiza Uralensis decoction extracts (LGE) on ulcerative colitis in children and adolescents. Methods Colitis was induced by DSS (Dextran Sulfate Sodium) in C57BL/6 mice. The sample mice were divided into group of four. The mice in the control group were not inflammation-induced. The control group was composed of untreated ulcerative colitis elicited mice. The mice in the experimental group were administered with Pentasa and another experimental group mice were treated with LGE after colitis elicitation. The effects on ulcerative colitis were evaluated by the morphological changes of colonic mucosa, decrease in the effect of pro-inflammatory cytokines ($TNF-{\alpha}$ and $NF-{\kappa}B$) and inflammatory cytokines (iNOS and COX-2) in the mucosa. Results LGE showed protective effects in DSS induced ulcerative colitis. LGE inhibited shortening of colon length and relieved the hemorrhagic erosion in colonic mucosa. LGE decreased pro-inflammatory cytokines ($TNF-{\alpha}$ and $NF-{\kappa}B$) and inflammatory cytokines (iNOS and COX-2). According to the GC/MS analysis, N-methyl pyrrolidone (NMP) was identified. Conclusions The result shows the clinical efficacy of LGE and demonstrates possible treatment options for ulcerative colitis. Further investigations for biological activity and chemical analysis of LGE will be needed.

• The Journal of Internal Korean Medicine
• /
• v.28 no.4
• /
• pp.972-977
• /
• 2007

Objectives : To see the effect of herbal medicine on ulcerative colitis by diagnosing ulcerative colitis as constipation due to stagnation of eum. Methods : We report here on a case of a patient who had abdominal pain, rectal urgency, diarrhea and hemafecia as chief complaints in December 2004 and was diagnosed with ulcerative colitis on January 20, 2007. The patient was treated with Pyungwijiyu-tang till Hwanggi was added on March 23rd of the same year. No change was made to the prescription since then. Results : After 14 weeks of herbal treatment the chief complaints decreased favorably and had no relapse. Conclusions : In this case, we recognized that the herbal medication could be effective for the clinical symptoms of ulcerative colitis. It was effective in decreasing or maintaining the symptoms of patients and in improving quality of life.

• The Journal of Internal Korean Medicine
• /
• v.28 no.4
• /
• pp.911-918
• /
• 2007

This study is a clinical report of one patient with symptoms remaining after western medical therapy for ulcerative colitis. Ulcerative colitis, a diffuse inflammatory disease of the mucosal lining of the colon and rectum, is characterized by a remitting and relapsing course. Therefore treatment is difficult and the proper treatment typically isn't established. We provided acupuncture-moxibustion therapy 28 times and prescribed Dansamboheol-tang gagam, which functions by nourishing the blood (補血), strengthening the spleen (健脾), adjustment of ki (理氣), removal of extravasated blood (祛瘀), and warming of the kidney (溫腎), for 30 days. The patient improved in quality of life and the symptoms disappeared. This study suggests that Dansamboheol-tang gagam, acupuncture, and moxibustion treatment has an effect on improving the symptoms remaining after western medical therapy for ulcerative colitis.

• The Journal of Internal Korean Medicine
• /
• v.38 no.6
• /
• pp.944-954
• /
• 2017

Objectives: This study investigated the anti-inflammatory effects of Jageum-jung extract on Dextran sulfate sodium (DSS-induced) ulcerative colitis in mice. Methods: Ulcerative colitis was induced by DSS in Balb/C male mice. Ten mice were assigned to each of four groups: Ctrl (control), UE (ulcerative colitis-induced), PT (treated with pentasaccharide after induction of ulcerative colitis), and JT (treated with Jageum-jung extract after induction of ulcerative colitis). The effects of Jageum-jung extract were measured by restoration of the length of the intestine, degree of mucosal damage as seen with histochemistry, and changes of p-IkB, iNOS, COX-2, and caspase-3 determined by immunohistochemistry. Results: The recovered intestinal length of the JT group was longer than that of the UE group. In the colon mucosa of JT group, hemorrhagic lesions were reduced, and the mucus barrier was recovered. This group also showed inhibited production of inflammatory enzymes (iNOS, COX-2) through regulation of proinflammatory enzyme (NF-kB, p65) activity in the colon. In addition, caspase 3 activation induced apoptosis. By GC/MS analysis, azetidine was identified. Conclusions: This study confirmed the anti-inflammatory effects of jageum-jung extract, and suggests the possibility of using Jageum-jung extract to treat ulcerative colitis. Further experiments and research on the mechanism of Jageum-jung effects are needed.

• The Journal of Internal Korean Medicine
• /
• v.38 no.6
• /
• pp.1021-1034
• /
• 2017

Objectives: The aim of this study was to investigate the effects of Gaejigayonggolmoryo-tang (GYT) on ulcerative colitis induced by dextran sodium sulfate (DSS) in mice. Methods: Colitis was induced by free drinking of 5% DSS in six-week-old male ICR mice. The experimental groups were the sample group, the control group, and the normal group. The sample group was treated with GYT for three days after being was given 5% DSS for five days. The control group was given water, instead of GYT, for three days after the five days of 5% DSS. The normal group was untreated (not given 5% DSS), for comparison purposes. Results: Cellular experiments showed that GYT inhibits the expression of the inflammatory enzymes COX-2 and iNOS, and the production of NO. Based on the primary cellular experiments, the effects of GYT on ulcerative colitis induced by DSS of mouse tissues were investigated. GYT reduced tissue damage and apoptosis by inhibiting the expression of the inflammatory enzymes $NF-{\kappa}B$ p65, COX-2, and iNOS. In the cellular experiment, GYT was more effective in inhibiting the expression of COX-2 than in inhibiting the expression of iNOS. GYT was evidently effective in tissues in inhibiting the expression of COX-2. Conclusions: Based on the results here, GYT may have therapeutic effects on ulcerative colitis induced by DSS. GYT is worthy of research and development as a COX-2 inhibitor and a potential drug for inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.

• The Journal of Pediatrics of Korean Medicine
• /
• v.29 no.3
• /
• pp.54-64
• /
• 2015

Objectives : This study was to investigate the anti-oxidative and anti-inflammatory effect of Lonicera japonica water extracts (LE) on Ulcerative Colitis Induced by DSS (Dextran Sulfate Sodium) in Mice. Methods : Colitis was induced by DSS in Balb/c mice. The sample group was divided into three. The mice in control group were not inflammation-induced. The pathological group was composed of untreated colitis elicited mice. The experimental group was administered Lonicera japonica water extracts (LE) after colitis elicitation. The effects on ulcerative colitis were evaluated the anti-oxidant effect, inhibition of COX-2 mRNA expression, the morphological change of colonic mucosa, decrease effect of HSP 70 and COX-2 in mucosa. Results : The SOD ability of LE was dose-dependently increased and the LPS-induced COX-2 mRNA expression of LE was dose-dependently decreased. LE showed the protective effects on DSS-induced experimental colitis. LE inhibited shortening of colon length, the hemorrhagic erosion in colonic mucosa. LE also showed the decrease effect for HSP70 and COX-2 in mucosa. Conclusions : The current results demonstrate the clinical utility of LE in traditional medicine and indicate the possible treatments for ulcerative colitis from natural products. Further investigations for exact mechanisms will be needed.

• Korean Journal of Clinical Pharmacy
• /
• v.30 no.2
• /
• pp.102-112
• /
• 2020

Objective: To analyze the prescription patterns for the treatment of ulcerative colitis (UC) and to investigate factors co-occurring with systemic corticosteroid use. Methods: We used patient-level data from Korean National Health Insurance claims database to identify patients diagnosed with UC (ICD-10 code : K51) and their medications prescribed for UC between January 1 and Decemeber 31, 2017. We found that medications for UC treatment were 5-aminosalicylic acid (5-ASA), immunomodulators, biologics, and corticosteroids. We presented the prescription pattern according to the sex, age group, type of health insurance, site of UC, type of medical institution, and concomitant medication. To evaluate factors associated with prescription of systemic corticosteroids for UC, we used a multivariate logistic regression model to estimate adjusted odds ratios (aORs) and their 95% confidence intervals (CIs). Results: Of 1,469 UC patients, 74.5% used 5-ASA and 15.2% used systemic corticosteroids. 5-ASA constituted 77.5% of all prescriptions and systemic corticosteroids accounted for 13.1%. The most widely used therapy was 5-ASA monotherapy (54.8%), followed by a double therapy with 5-ASA and immunomodulators (8.2%) or 5-ASA and systemic corticosteroids (7.2%). Systemic corticosteroids were more likely to be prescribed with immunomodulators (aOR=1.88, 95% CI=1.54-2.28) and biologics (aOR=2.82, 95% CI=2.28-3.50) than without them. Conclusions: We found that 15.2% of UC patients were prescribed with a systemic corticosteroid, which is less than reported previously. Systemic corticosteroids were more likely to be prescribed with immunomodulators and biologics.