• International Journal of Advanced Culture Technology
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• v.6 no.4
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• pp.97-108
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• 2018

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 moleculesthrough suppression both mitogen-activated protein kinases(MAPK) and nuclear factor-kappa B ($NF-{\kappa}B$) signaling pathways, and prevented the apoptosis of colon. Moreover, SRE administration significantly led to the up-regulation of anti-oxidant 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.

• 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.

• International Journal of Internet, Broadcasting and Communication
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• v.13 no.2
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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.

• BMB Reports
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• v.53 no.5
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• pp.284-289
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• 2020

Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

• Toxicological Research
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• v.32 no.2
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• pp.133-140
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• 2016

Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

• Molecules and Cells
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• v.38 no.11
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• pp.1013-1021
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• 2015

Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immune-modulating drug that is used in rheumatology and inflammatory bowel disease. Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS.

• The Journal of the Convergence on Culture Technology
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• v.5 no.3
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• pp.317-326
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• 2019

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 MAPK) and nuclear factor-kappa B (NF-${\kappa}B$) signaling pathways, and prevented the apoptosis of colon. Moreover, SRE administration significantly led to the up-regulation of anti-oxidant 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 sulfasalazin.

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

• Journal of Oral Medicine and Pain
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• v.37 no.3
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• pp.155-159
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• 2012

Background Oral lichen planus (OLP) is a chronic inflammatory disease characterized by cell-mediated immune responses, but the exact cause is unknown. Sulfasalazine has shown efficacy in the treatment of cutaneous lichen planus. Objective Our purpose was to assess the usefulness of sulfasalazine in treatment of OLP resistant to corticosteroid therapy. This study provides a new option for controlling OLP symptoms. Methods Two patients with the symptomatic reticular form of OLP were treated with 30 mg/5 ml of topical sulfasalazine for 8 to 15 weeks and were evaluated for symptom severity using a numerical analog scale during each week of treatment. The lesion size was measured using a 2 $mm^2$ grid. Results After 2 weeks of application, both patients reported improvements in their symptoms and lesions. Most of the lesions disappeared after 8 weeks of treatment without any side effects. Conclusion Topical sulfasalazine can be a successful treatment option for patients with oral lichen planus resistant to steroid therapy.

• Journal of Korean Traditional Oncology
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• v.17 no.2
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• pp.17-22
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• 2012

Background : Sulfasalazine for treating ulcerative colitis has a clinical limitation due to its adverse effects. This case is about a patient with ulcerative colitis who could not tolerate sulfasalazine and was improved by Do-che decoction-based Korean medicine. Method and Results : Purulent and bloody diarrhea more than 20 times a day, mild fever, chilling and tenesmus were main symptoms of this patient who was diagnosed as ulcerative colitis 10 years ago. Do-che decoction-based Korean medicine which was recommended for purulent and bloody diarrhea in Dong-Ui-Bo-Gam, the classic literature of Traditional Korean Medicine was given to the patient for more than 1 month. After treatment, the frequency of purulent and bloody diarrhea, tenesmus and fever was decreased remarkably, and C-reactive protein, erythrocyte sedimentation rate, white blood cell count and maximum temperature also dropped to the normal range. Conclusion : Do-che decoction-based Korean medicine has a potential effect and may be a alternative therapeutic option in patients with ulcerative colitis who cannot tolerate sulfasalazine due to its adverse effects.