{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:34:07Z","timestamp":1783420447040,"version":"3.54.6"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T00:00:00Z","timestamp":1542326400000},"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":["2017R1D1A3B03036020"],"award-info":[{"award-number":["2017R1D1A3B03036020"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Reflux esophagitis (RE) is a gastrointestinal disease caused by the reflux of gastric acid and stomach contents, and it leads to esophageal damage. Therefore, it is necessary to study the improvement of esophageal damage on a RE-induced model. The present study was accomplished to demonstrate the protective effects of a dichloromethane fraction of Geranium koreanum (DGK) plant on esophageal damage in an acute RE rat model. First, we examined the potential of anti-inflammatory effects of various fractions measured by cell cytotoxicity, morphological changes and nitric oxide (NO) production on lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Then, to evaluate the protective effects on RE, rats were partitioned into the following groups: normal control, RE-induced control and RE rats pre-treated with DGK 100 and 200 mg\/kg body weight. The esophageal mucosal ulcer ratio was measured by the Image J program and histological changes were examined using a hematoxylin and eosin staining of the esophageal mucosa. The expression of pro-inflammatory proteins, cytokines and tight junction proteins involved in the esophageal mucosal damage were investigated using Western blotting and an enzyme-linked immunosorbent assay (ELISA) kit with esophagus tissue. DGK chemical profile and phenolic contents were analyzed by liquid chromatography-mass spectrometry (LC-MS\/MS). The results showed that DGK exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting NO production. Additionally, the results in vivo showed that improvement effects of DGK on esophageal mucosal damage. The expression of inflammatory proteins involved in nuclear factor \u03baB (NF-\u03baB) signaling pathways and tight junction protein (claudin-4 and -5) were significantly decreased in esophageal mucosa. We found the potential of DGK as source of replacement therapy products for inflammatory and RE disease.<\/jats:p>","DOI":"10.3390\/ijms19113622","type":"journal-article","created":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T11:48:31Z","timestamp":1542368911000},"page":"3622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dichloromethane Extracts of Geranium Koreanum Kom. Alleviates Esophagus Damage in Acute Reflux Esophagitis-Induced Rats by Anti-Inflammatory Activities"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4229-4356","authenticated-orcid":false,"given":"Hyeon Hwa","family":"Nam","sequence":"first","affiliation":[{"name":"Department of Crop Science &amp; Biotechnology, Chonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Crop Science &amp; Biotechnology, Chonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Kil","family":"Choo","sequence":"additional","affiliation":[{"name":"Department of Crop Science &amp; Biotechnology, Chonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jep.2010.12.004","article-title":"Effects of morinda citrifolia aqueous fruit extract and its biomarker scopoletin on reflux esophagitis and gastric ulcer in rats","volume":"134","author":"Mahattanadul","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3164\/jcbn.40.13","article-title":"Inflammation and oxidative stress in gastroesophageal reflux disease","volume":"40","author":"Yoshida","year":"2007","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.6116\/kjh.2015.30.4.37.","article-title":"Improving effect of a combined extract of rhei rhizoma and glycyrrhizae rhizoma through anti-oxidative stress in reflux esophagitis rats","volume":"30","author":"Kim","year":"2015","journal-title":"Kor. J. Herbol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1111\/j.1572-0241.2000.03175.x","article-title":"The role of diet and lifestyle measures in the pathogenesis and treatment of gastroesophageal reflux disease","volume":"95","author":"Meining","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1007\/s10620-010-1166-9","article-title":"Management of recurrence of symptoms of gastroesophageal reflux disease: Synergistic effect of rebamipide with 15 mg lansoprazole","volume":"55","author":"Yoshida","year":"2010","journal-title":"Dig. Dis. Sci."},{"key":"ref_6","first-page":"449","article-title":"Meta-analyses: Does long-term PPI use increase the risk of gastric premalignant lesions?","volume":"16","author":"Layli","year":"2013","journal-title":"Arch. Iran. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pathophys.2018.01.001","article-title":"Protective effects of Artemisia campestris extract against gastric acid reflux-induced esophageal mucosa injuries","volume":"25","author":"Jabri","year":"2018","journal-title":"Pathophysiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S1995-7645(14)60035-3","article-title":"Protection effect Xuanfudaizhetang on reflux esophagitis in rats","volume":"7","author":"Lian","year":"2014","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shin, M.R., Seo, B.I., Son, C.G., Roh, S.S., and An, H.J. (2017). Banhasasim-tang treatment reduces the severity of esophageal mucosal ulcer on chronic acid reflux esophagitis in rats. BioMed Res. Int., 7157212.","DOI":"10.1155\/2017\/7157212"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cbi.2016.05.014","article-title":"Inhibitory effects of geraniin on LPS-induced inflammation via regulating NF-\u03baB and Nrf2 pathways in RAW 264.7 Cells","volume":"253","author":"Wang","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jep.2016.06.019","article-title":"PDK1 in NF-\u03baB signaling is a target of Xanthium strumarium methanolic extract-mediated anti-inflammatory activities","volume":"190","author":"Hossen","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.3892\/mmr.2014.2298","article-title":"Anti-inflammatory effects of Perilla frutescens leaf extract on lipopolysaccaharide-stimulated RAW 264.7 cells","volume":"10","author":"Huang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1053\/j.gastro.2009.07.055","article-title":"Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury","volume":"137","author":"Souza","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"420","DOI":"10.4062\/biomolther.2014.066","article-title":"Protective effects of chlorogenic acid against experimental reflux esophagitis in rats","volume":"22","author":"Kang","year":"2014","journal-title":"Biomol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1007\/BF01308601","article-title":"Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats","volume":"38","author":"Klein","year":"1933","journal-title":"Dig. Dis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s10620-005-2813-4","article-title":"Prevention by rebamipide of acute reflux esophagitis in rats","volume":"50","author":"Katada","year":"2005","journal-title":"Dig. Dis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1136\/gut.50.4.451","article-title":"Diversity in the oesophageal phenotypic response to gastro-oesophageal reflux: Immunological determinants","volume":"50","author":"Fitzgerald","year":"2002","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s00535-009-0180-1","article-title":"Rikkunshito, a traditional Japanese medicine, may relieve abdominal symptoms in rats with experimental esophagitis by improving the barrier function of epithelial cells in esophageal mucosa","volume":"45","author":"Miwa","year":"2010","journal-title":"J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1161\/ATVBAHA.109.197582","article-title":"Claudin-5 as a novel estrogen target in vascular endothelium","volume":"30","author":"Burek","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1083\/jcb.200207050","article-title":"Distinct claudins and associated PDZ proteins form different autotypic tight junctions in myelinating Schwann cells","volume":"159","author":"Poliak","year":"2002","journal-title":"J. Cell Ciol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s00384-009-0737-8","article-title":"Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease","volume":"24","author":"Amasheh","year":"2009","journal-title":"Int. J. Colorectal. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e185","DOI":"10.1016\/j.jss.2010.02.010","article-title":"The expression of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue","volume":"167","author":"Jung","year":"2011","journal-title":"J. Surg. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.yjmcc.2004.11.025","article-title":"Claudin-5 localizes to the lateral membranes of cardiomyocytes and is altered in utrophin\/dystrophin-deficient cardiomyophathic mice","volume":"38","author":"Sanford","year":"2005","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jep.2007.08.005","article-title":"Estimation of antinociceptive and anti-inflammatory activity on Geranium pretense subp. Finitimum and its phenolic compounds","volume":"114","author":"Kupeli","year":"2007","journal-title":"J. Ethopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117","DOI":"10.14405\/kjvr.2015.55.2.117","article-title":"Antibacterial activities of bark extracts from Fraxinus rhynchophylla Hance and Geranium koreanum Kom. against clinical strains of Clostridium perfringens in chickens","volume":"55","author":"Oh","year":"2015","journal-title":"Korean J. Vet. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.yexcr.2014.07.005","article-title":"Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model","volume":"330","author":"Xiao","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jep.2009.08.004","article-title":"Anti-inflammatory activity of ethanol extract from Geranium sibiricum Linne","volume":"126","author":"Shim","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_28","first-page":"194","article-title":"Anti-inflammatory activities fraction from Geranium nepalense and related polyphenols","volume":"6","author":"Lu","year":"2013","journal-title":"Drug Discov. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"663","DOI":"10.3892\/etm.2013.1202","article-title":"Berberine protects against esophageal mucosal damage in reflux esophagitis by suppressing proinflammatory cytokines","volume":"6","author":"Choo","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5009\/gnl17078","article-title":"Additive effects of rebamipide plus protone pump inhibitors on the expression of tight junction proteins in a rat model of gastro-esophageal reflux disease","volume":"12","author":"Gweon","year":"2017","journal-title":"Gut. Liver"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zong, Y., Sun, L., Liu, B., Deng, Y.S., Zhan, D., Chen, Y.L., He, Y., Liu, J., Zhang, Z.J., and Sun, J. (2012). Resveratrol inhibits LPS-induced MAPKs activation via activation of the phosphatidylinositol 3-kinase pathway murine Raw 264.7 macrophage cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044107"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"517","DOI":"10.5056\/jnm16178","article-title":"Relationship between salivary pepsin concentration and esophageal mucosal integrity in patients with gastroesophageal reflux disease","volume":"23","author":"Li","year":"2017","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.biopha.2018.04.007","article-title":"Evidence for gastroprotective, anti-infalmmatory and antioxidant potential of methanolic extract of Cordia dichotoma leaves on indomethacin and stress induced gastric lesions in Wistar rats","volume":"103","author":"Hatware","year":"2018","journal-title":"BioMed Pharmacother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/jssc.201100006","article-title":"One-step separation and purification of hydrolysable tannis from Geranium wilfordii Maxim by adsorption Chromatography on cross-linked 12% agarose gel","volume":"34","author":"Liu","year":"2011","journal-title":"J. Sep. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22835","DOI":"10.18632\/oncotarget.15227","article-title":"Geraniin attenuates LPS-induced acute lung injury via inhibiting NF-\u03baB and activating Nrf2 Signaling pathway","volume":"8","author":"Zhu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, X., Chen, Z., Li, X., Jiang, Z.K., Zhao, Y.Q., and Ping, F.F. (2017). Geraniin suppresses ovarian cancer growth through inhibition of NF-\u03baB activation and downregulation of Mcl-1 expression. J. Biochem. Mol. Toxicol., 31.","DOI":"10.1002\/jbt.21929"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"560","DOI":"10.5483\/BMBRep.2017.50.11.060","article-title":"Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1","volume":"50","author":"Aayadi","year":"2017","journal-title":"BMB Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1039\/C6FO01075J","article-title":"Cheminal characterization and bioactive properties of aqueous and organic extracts of Geranium robertianum L.","volume":"7","author":"Graca","year":"2016","journal-title":"Food Funct."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.3892\/ijmm.2015.2128","article-title":"The inhibitory effects of Geranium thunbergii on imterferom-\u03b3- and LPS-induced inflammatory responses are mediated by Nrf2 activation","volume":"35","author":"Choi","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.1021\/jf904593n","article-title":"Antioxidant activities and xanthine oxidase inhibitory effects of extracts and main polyphenolic compounds obtained from Geranium Sibiricum L.","volume":"58","author":"Wu","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1039\/C7FO00881C","article-title":"Antioxidant and anti-inflammatory activities of Geranium robertianum L. decoctions","volume":"8","author":"Ctarino","year":"2017","journal-title":"Food Funct."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:30:13Z","timestamp":1760196613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/11\/3622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,16]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["ijms19113622"],"URL":"https:\/\/doi.org\/10.3390\/ijms19113622","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,16]]}}}