{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:55:53Z","timestamp":1791824153600,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1F1A1073313"],"award-info":[{"award-number":["NRF-2022R1F1A1073313"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 \u03bcL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-\u03baB\/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC.<\/jats:p>","DOI":"10.3390\/ijms25105076","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T09:03:38Z","timestamp":1715072618000},"page":"5076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Simultaneous Treatment of 5-Aminosalicylic Acid and Treadmill Exercise More Effectively Improves Ulcerative Colitis in Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Jun-Jang","family":"Jin","sequence":"first","affiliation":[{"name":"Team of Efficacy Evaluation, Orient Genia Inc., Seongnam 13201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il-Gyu","family":"Ko","sequence":"additional","affiliation":[{"name":"Research Support Center, School of Medicine, Keimyung University, Deagu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakkyong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Team of Efficacy Evaluation, Orient Genia Inc., Seongnam 13201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8867-8822","authenticated-orcid":false,"given":"Sang-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers, The Stat University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-0843","authenticated-orcid":false,"given":"Yong-Seok","family":"Jee","sequence":"additional","affiliation":[{"name":"Research Institute of Sports and Industry Science, Hanseo University, Seosan 31962, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-2922","authenticated-orcid":false,"given":"Hyeon","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, College of Engineering, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4638-413X","authenticated-orcid":false,"given":"Su Bee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Won","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1056\/NEJMra0804647","article-title":"Inflammatory bowel disease","volume":"361","author":"Abraham","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/01.MIB.0000195385.19268.68","article-title":"Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities","volume":"1","author":"Hanauer","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/1751-2980.12449","article-title":"Epidemiology of inflammatory bowel diseases from west to east","volume":"18","author":"Vegh","year":"2017","journal-title":"J. Dig. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.intimp.2018.02.012","article-title":"Andrographolide derivative CX-10 ameliorates dextran sulphate sodium-induced ulcerative colitis in mice: Involvement of NF-\u03baB and MAPK signaling pathways","volume":"57","author":"Gao","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1476-9255-9-30","article-title":"Effect of exercise on chemically-induced colitis in adiponectin deficient mice","volume":"9","author":"Saxena","year":"2012","journal-title":"J. Inflamm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.intimp.2017.06.022","article-title":"Protective effects of paeoniflorin on TNBS-induced ulcerative colitis through inhibiting NF-\u03baB pathway and apoptosis in mice","volume":"50","author":"Gu","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1089\/bfm.2018.0111","article-title":"Determination of mesalamine levels in human milk as a function of dose","volume":"14","author":"Datta","year":"2019","journal-title":"Breastfeed. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s12170-015-0463-4","article-title":"Effects of exercise on gene expression of inflammatory markers in human peripheral blood cells: A systematic review","volume":"9","author":"Gjevestad","year":"2015","journal-title":"Curr. Cardiovasc. Risk Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.bbi.2010.05.001","article-title":"Freewheel training decreases pro- and increases anti-inflammatory cytokine expression in mouse intestinal lymphocytes","volume":"24","author":"Pervaiz","year":"2010","journal-title":"Brain Behav. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/apha.12534","article-title":"Voluntary exercise protects against ulcerative colitis by up-regulating glucocorticoid-mediated PPAR-\u03b3 activity in the colon in mice","volume":"215","author":"Liu","year":"2015","journal-title":"Acta Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.intimp.2016.10.021","article-title":"Zanthoxylum bungeanum pericarp extract prevents dextran sulfate sodium-induced experimental colitis in mice via the regulation of TLR4 and TLR4-related signaling pathways","volume":"41","author":"Zhang","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1089\/dna.2019.4737","article-title":"Effect of the sphingosine kinase 1 selective inhibitor, PF543 on dextran sodium sulfate-induced colitis in mice","volume":"38","author":"Sun","year":"2019","journal-title":"DNA Cell Biol."},{"key":"ref_13","first-page":"587","article-title":"Functional relevance of soluble TNF-\u03b1, transmembrane TNF-\u03b1 and TNF-signal transduction in gastrointestinal diseases with special reference to inflammatory bowel diseases","volume":"40","author":"Holtmann","year":"2002","journal-title":"Gastroenterol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9300","DOI":"10.3748\/wjg.v22.i42.9300","article-title":"Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases","volume":"22","author":"Billmeier","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/ibd.20148","article-title":"Il-6 signaling in inflammatory bowel disease: Pathophysiological role and clinical relevance","volume":"13","author":"Mudter","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.biopha.2010.01.013","article-title":"Effect of low molecular weight heparin rectal suppository on experimental ulcerative colitis in mice","volume":"64","author":"Luo","year":"2010","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1385\/CRIAI:28:3:187","article-title":"Involvement of IL-6 in the pathogenesis of inflammatory bowel disease and colon cancer","volume":"28","author":"Atreya","year":"2005","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bilski, J., Mazur-Bialy, A., Wojcik, D., Magierowski, M., Surmiak, M., Kwiecien, S., Magierowska, K., Hubalewska-Mazgaj, M., Sliwowski, Z., and Brzozowski, T. (2019). Effect of forced physical activity on the severity of experimental colitis in normal weight and obese mice. Involvement of oxidative stress and proinflammatory biomarkers. Nutrients, 11.","DOI":"10.3390\/nu11051127"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/14712598.2019.1666101","article-title":"Modern use of 5-aminosalicylic acid compounds for ulcerative colitis","volume":"20","author":"Roda","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36099","DOI":"10.1074\/jbc.M505291200","article-title":"Tumor necrosis factor (TNF) \u03b1 increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2","volume":"280","author":"Theiss","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Akanda, M.R., Kim, I.S., Ahn, D., Tae, H.J., Nam, H.H., Choo, B.K., Kim, K., and Park, B.Y. (2018). Anti-inflammatory and gastroprotective roles of rabdosia inflexa through downregulation of pro-inflammatory cytokines and MAPK\/NF-\u03baB signaling pathways. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020584"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.intimp.2017.05.040","article-title":"\u03b1-Mangostin ameliorates dextran sulfate sodium-induced colitis through inhibition of NF-\u03baB and MAPK pathways","volume":"49","author":"You","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5768","DOI":"10.1039\/C9FO00664H","article-title":"The dietary freeze-dried fruit powder of Actinidia argute ameliorates dextran sulphate sodium-induced ulcerative colitis in mice by inhibiting the activation of MAPKs","volume":"10","author":"Lian","year":"2019","journal-title":"Food Funct."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13133","DOI":"10.1021\/acs.jafc.8b03942","article-title":"Protective effect of naringin on DSS-induced ulcerative colitis in mice","volume":"66","author":"Cao","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1365-2796.2008.01953.x","article-title":"NF-\u03baB in inflammatory bowel disease","volume":"263","author":"Atreya","year":"2008","journal-title":"J. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","article-title":"Regulation and function of NF-\u03baB transcription factors in the immune system","volume":"27","author":"Vallabhapurapu","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6685","DOI":"10.1038\/sj.onc.1209934","article-title":"I\u03baB kinase complexes: Gateways to NF-\u03baB activation and transcription","volume":"25","author":"Scheidereit","year":"2006","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.cytogfr.2011.11.002","article-title":"Regulation of TNF-induced NF-\u03baB activation by different cytoplasmic ubiquitination events","volume":"22","author":"Verhelst","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3389\/fphys.2018.00636","article-title":"Moderate Exercise Suppresses NF-\u03baB Signaling and Activates the SIRT1-AMPK-PGC1\u03b1 Axis to Attenuate Muscle Loss in Diabetic db\/db Mice","volume":"29","author":"Liu","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.metabol.2017.03.001","article-title":"Effect of a single bout of aerobic exercise on high-fat meal-induced inflammation","volume":"71","author":"Fuller","year":"2017","journal-title":"Metabolism"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1515\/tnsci-2022-0268","article-title":"Pre-ischemic exercise prevents inflammation and apoptosis by inhibiting MAPK pathway in ischemic stroke","volume":"13","author":"Gao","year":"2022","journal-title":"Transl. Neurosci."},{"key":"ref_32","first-page":"3204","article-title":"Current treatment of ulcerative colitis","volume":"17","author":"Meier","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/01.MIB.0000217334.30689.3e","article-title":"Regulation of apoptosis during homeostasis and disease in the intestinal epithelium","volume":"12","author":"Edelblum","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1053\/j.gastro.2011.05.032","article-title":"p53 and PUMA independently regulate apoptosis of intestinal epithelial cells in patients and mice with colitis","volume":"141","author":"Dirisina","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1165\/rcmb.2002-0269OC","article-title":"Particulate matter induces alveolar epithelial cell DNA damage and apoptosis: Role of free radicals and the mitochondria","volume":"29","author":"Upadhyay","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Crespo, I., San-Miguel, B., Prause, C., Marroni, N., Cuevas, M.J., Gonz\u00e1lez-Gallego, J., and Tu\u00f1\u00f3n, M.J. (2012). Glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050407"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1021\/np4006772","article-title":"Inhibitory effect of the gallotannin corilagin on dextran sulfate sodium-induced murine ulcerative colitis","volume":"76","author":"Xiao","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1007\/s12013-013-9642-4","article-title":"Caspase-3 is involved in IFN-\u03b3- and TNF-\u03b1-mediated MIN6 cells apoptosis via NF-\u03baB\/Bcl-2 pathway","volume":"67","author":"Cao","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s12974-018-1271-9","article-title":"Inhibiting aberrant p53-PUMA feedback loop activation attenuates ischaemia reperfusion-induced neuroapoptosis and neuroinflammation in rats by downregulating caspase 3 and the NF-\u03baB cytokine pathway","volume":"15","author":"Li","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nprot.2007.41","article-title":"Chemically induced mouse models of intestinal inflammation","volume":"2","author":"Wirtz","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"338","DOI":"10.2174\/156720112801323062","article-title":"Foam preparations for the treatment of ulcerative colitis","volume":"9","author":"Loew","year":"2012","journal-title":"Curr. Drug Deliv."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, Y.H., Zhang, M., Xiao, H.T., Fu, H.B., Ho, A., Lin, C.Y., Huang, Y., Lin, G., and Bian, Z.X. (2015). Addition of berberine to 5-aminosalicylic acid for treatment of dextran sulfate sodium-induced chronic colitis in C57BL\/6 mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144101"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/nprot.2017.044","article-title":"Chemically induced mouse models of acute and chronic intestinal inflammation","volume":"12","author":"Wirtz","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"327","DOI":"10.12965\/jer.1836248.124","article-title":"Late starting treadmill exercise improves spatial leaning ability through suppressing CREP\/BDNF\/TrkB signaling pathway following traumatic brain injury in rats","volume":"14","author":"Ko","year":"2018","journal-title":"J. Exerc. Rehabil."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"350","DOI":"10.12965\/jer.2244504.252","article-title":"Polydeoxyribonucleotide ameliorates alcoholic liver injury though suppressing phosphatidylinositol 3-kinase\/protein kinase B signaling pathway in mice","volume":"18","author":"Cho","year":"2022","journal-title":"J. Exerc. Rehabil."},{"key":"ref_46","first-page":"527","article-title":"An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis","volume":"258","author":"Wallace","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kim, S.E., Ko, I.G., Jin, J.J., Hwang, L., Kim, C.J., Kim, S.H., Han, J.H., and Jeon, J.W. (2020). Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats. BioMed Res. Int., 21.","DOI":"10.1155\/2020\/2169083"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/his.13400","article-title":"A novel histological examination with dynamic three-dimensional reconstruction from multiple immunohistochemically stained sections of a PD-L1-positive colon cancer","volume":"72","author":"Korehisa","year":"2018","journal-title":"Histopathology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1751-2980.2012.00607.x","article-title":"Dynamic progress of 2,4,6-trinitrobenzene sulfonic acid induced chronic colitis and fibrosis in rat model","volume":"13","author":"Zhu","year":"2012","journal-title":"J. Dig. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"28","DOI":"10.12965\/jer.2244002.001","article-title":"Treadmill exercise ameliorates ethanol with lipopolysaccharide and carbon tetrachloride-mediated liver injury in mice","volume":"18","author":"Kim","year":"2022","journal-title":"J. Exerc. Rehabil."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"234","DOI":"10.12965\/jer.2142466.233","article-title":"Treadmill exercise ameliorates impairment of spatial learning memory in pups born to old and obese mother rats","volume":"17","author":"Kim","year":"2021","journal-title":"J. Exerc. Rehabil."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5076\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:40:52Z","timestamp":1760107252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105076"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105076","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,7]]}}}