{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:00Z","timestamp":1760146200680,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chong Kun Dang Pharmaceutical Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Postoperative ileus (POI) is a delay in gastrointestinal transit following surgery that leads to various complications. There is limited understanding of its effective treatment options. CKD-495 and eupacidin are natural products licensed for treating mucosal lesions in acute and chronic gastritis; however, little is known about their effects on intestinal permeability. This study evaluated the effects of CKD-495, eupacidin, and its components (eupatilin and cinnamic acid) on intestinal permeability in an animal model of POI. Materials and Methods: Guinea pigs underwent surgical procedures and were randomly assigned to different treatment groups. Drugs were administered orally prior to surgery. Intestinal permeability, leukocyte count, and the expression of calprotectin and tight junction proteins were measured in the harvested ileum tissue. Results: The intestinal permeability and leukocyte count were higher in the POI group than in the control group. The pre-administration of CKD-495, cinnamic acid, eupacidin, and eupatilin effectively prevented these changes in the POI model. No significant differences were observed in the expression of tight junction proteins. Conclusions: CKD-495, cinnamic acid, eupacidin, and eupatilin exerted protective effects against increased intestinal permeability and inflammation in an animal model of POI. These natural products have potential as therapeutic options for the treatment of POI.<\/jats:p>","DOI":"10.3390\/medicina60101707","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:03:49Z","timestamp":1729227829000},"page":"1707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of CKD-495, Eupacidin, and Their Marker Compounds on Altered Permeability in a Postoperative Ileus Animal Model"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-7692","authenticated-orcid":false,"given":"Min-Jae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06274, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-9484","authenticated-orcid":false,"given":"Zahid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06274, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06274, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyojin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06274, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref_1","first-page":"e22652","article-title":"Prevention and management of postoperative ileus: A review of current practice","volume":"14","author":"Khawaja","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1007\/s11605-015-2877-1","article-title":"Postoperative ileus\u2014More than just prolonged length of stay?","volume":"19","author":"Tevis","year":"2015","journal-title":"J. Gastrointest. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jamcollsurg.2009.09.028","article-title":"Postoperative ileus: It costs more than you expect","volume":"210","author":"Asgeirsson","year":"2010","journal-title":"J. Am. Coll. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.jviscsurg.2016.08.010","article-title":"Postoperative ileus: Pathophysiology, incidence, and prevention","volume":"153","author":"Venara","year":"2016","journal-title":"J. Visc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF01537233","article-title":"Postoperative ileus","volume":"35","author":"Livingston","year":"1990","journal-title":"Dig. Dis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/ans.17297","article-title":"Post-operative ileus: Definitions, mechanisms and controversies","volume":"92","author":"Wells","year":"2022","journal-title":"ANZ J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e14308","DOI":"10.1111\/nmo.14308","article-title":"The role of vagal innervation on the early development of postoperative ileus in mice","volume":"34","author":"Brandlhuber","year":"2022","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.5056\/jnm17012","article-title":"Inflammation, impaired motility, and permeability in a guinea pig model of postoperative ileus","volume":"24","author":"Lee","year":"2018","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"639","DOI":"10.5056\/jnm21018","article-title":"Altered intestinal permeability and drug repositioning in a post-operative ileus guinea pig model","volume":"27","author":"Kim","year":"2021","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jep.2008.03.010","article-title":"The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: Involvement of ho-1 and erk","volume":"118","author":"Song","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10286020.2018.1492565","article-title":"Eupatilin: A natural pharmacologically active flavone compound with its wide range applications","volume":"22","author":"Nageen","year":"2020","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e35926","DOI":"10.1097\/MD.0000000000035926","article-title":"Efficacy and safety of ckd-495 in acute and chronic gastritis: A phase iii superiority clinical trial","volume":"102","author":"Seo","year":"2023","journal-title":"Medicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1142\/S0192415X06004041","article-title":"Antimicrobial activities of cinnamon oil and cinnamaldehyde from the Chinese medicinal herb Cinnamomum cassia blume","volume":"34","author":"Ooi","year":"2006","journal-title":"Am. J. Chin. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2174\/138955712801264792","article-title":"Antioxidant and antimicrobial activities of cinnamic acid derivatives","volume":"12","author":"Sova","year":"2012","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.2174\/092986711795471347","article-title":"Cinnamic acid derivatives as anticancer agents\u2014A review","volume":"18","author":"De","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ruwizhi, N., and Aderibigbe, B.A. (2020). Cinnamic acid derivatives and their biological efficacy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165712"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"406","DOI":"10.5009\/gnl15251","article-title":"The effect of da-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model","volume":"10","author":"Kwak","year":"2016","journal-title":"Gut Liver"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.lfs.2011.04.011","article-title":"Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages","volume":"88","author":"Choi","year":"2011","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jin, H.-G., Kim, K.-W., Li, J., Lee, D.Y., Yoon, D., Jeong, J.T., Kim, G.-S., Oh, H., An, R.-B., and Kim, Y.-C. (2022). Anti-inflammatory components isolated from Atractylodes macrocephala in lps-induced raw264.7 macrophages and bv2 microglial cells. Appl. Biol. Chem., 65.","DOI":"10.1186\/s13765-022-00673-2"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pontiki, E., and Hadjipavlou-Litina, D. (2018). Multi-target cinnamic acids for oxidative stress and inflammation: Design, synthesis, biological evaluation and modeling studies. Molecules, 24.","DOI":"10.3390\/molecules24010012"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Adisakwattana, S. (2017). Cinnamic acid and its derivatives: Mechanisms for prevention and management of diabetes and its complications. Nutrients, 9.","DOI":"10.3390\/nu9020163"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4292\/wjgpt.v14.i2.4","article-title":"Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation","volume":"14","author":"Jiang","year":"2023","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5217\/ir.2015.13.1.11","article-title":"Intestinal permeability regulation by tight junction: Implication on inflammatory bowel diseases","volume":"13","author":"Lee","year":"2015","journal-title":"Intest. 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