{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T21:55:10Z","timestamp":1774907710602,"version":"3.50.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["BK21 FOUR Program"],"award-info":[{"award-number":["BK21 FOUR Program"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2020R1l1A1A01052277"],"award-info":[{"award-number":["2020R1l1A1A01052277"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"2020 Post-Doc. Development Program"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>To investigate the role of tannin-enriched extracts of<jats:italic>Ecklonia cava<\/jats:italic>(TEE) on the regulation of oxidative balance and laxative activity in chronic constipation, we investigated alterations after exposure to TEE, on constipation phenotypes, muscarinic cholinergic regulation, and oxidative stress responses in the transverse colons of SD rats with loperamide (Lop)-induced constipation. This extract contains high levels of total condensed tannin content (326.5 mg\/g), and exhibited high inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. TEE treatment induced significant improvements in reactive oxygen species (ROS) production, superoxide dismutase (SOD) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation in primary smooth muscles of rat intestine cells (pRISMCs) and transverse colon of constipation model. Also, Lop+TEE treated groups showed alleviated outcomes for the following: most stool parameters, gastrointestinal transit, and intestine length were remarkably recovered; a similar recovery pattern was observed in the histopathological structure, mucin secretion, water channel expression and gastrointestinal hormones secretion in the transverse colon; expressions of muscarinic acetylcholine receptors M2\/M3 (mAChR M2\/M3) and their mediators on muscarinic cholinergic regulation were significantly recovered. Taken together, these results provide the first evidence that TEE stimulates oxidative stress modulation and muscarinic cholinergic regulation when exerting its laxative effects in chronic constipation models.<\/jats:p>","DOI":"10.1371\/journal.pone.0246363","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T18:34:48Z","timestamp":1614191688000},"page":"e0246363","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["Antioxidant activity and laxative effects of tannin-enriched extract of Ecklonia cava in loperamide-induced constipation of SD rats"],"prefix":"10.1371","volume":"16","author":[{"given":"Ji Eun","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun Ju","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Eun","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Eun","family":"Sung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Suk","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Seob","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-1725","authenticated-orcid":true,"given":"Dae Youn","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"pone.0246363.ref001","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative stress: harms and benefits for human health","volume":"2017","author":"G Pizzino","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0246363.ref002","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/apt.13257","article-title":"Chronic constipation-a warning sign for oxidative stress","volume":"42","author":"A Vermorken","year":"2015","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0246363.ref003","doi-asserted-by":"crossref","first-page":"368","DOI":"10.3748\/wjg.v11.i3.368","article-title":"Potential oxidative stress in children with chronic constipation","volume":"11","author":"JF Zhou","year":"2005","journal-title":"World J Gastroenterol"},{"key":"pone.0246363.ref004","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/MPG.0b013e31821eed83","article-title":"Prebiotics and oxidative stress in constipated rats","volume":"53","author":"Y Li","year":"2011","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"pone.0246363.ref005","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.biopha.2017.02.020","article-title":"Role of laxative and antioxidant properties of Malva sylvestris leaves in constipation treatment","volume":"89","author":"MA Jabri","year":"2017","journal-title":"Biomed Pharmacother"},{"key":"pone.0246363.ref006","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jep.2018.06.001","article-title":"Ficus carica aqueous extract alleviates delayed gastric emptying and recovers ulcerative colitis-enhanced acute functional gastrointestinal disorders in rats","volume":"224","author":"K Rtibi","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"pone.0246363.ref007","doi-asserted-by":"crossref","first-page":"946","DOI":"10.3390\/ijms20040946","article-title":"Anti-inflammatory response and muscarinic cholinergic regulation during the laxative effect of Asparagus cochinchinensis in loperamide-induced constipation of SD rats","volume":"20","author":"JE Kim","year":"2019a","journal-title":"Int J Mol Sci"},{"key":"pone.0246363.ref008","doi-asserted-by":"crossref","first-page":"e0161144","DOI":"10.1371\/journal.pone.0161144","article-title":"Gallotannin-enriched extract isolated from Galla rhois may be a functional candidate with laxative effects for treatment of loperamide-induced constipation of SD rats","volume":"11","author":"JE Kim","year":"2016","journal-title":"PLoS One"},{"key":"pone.0246363.ref009","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/1472-6882-13-333","article-title":"Aqueous extracts of Liriope platyphylla induced significant laxative effects on loperamide-induced constipation of SD rats","volume":"13","author":"JE Kim","year":"2013","journal-title":"BMC Complement Altern Med"},{"key":"pone.0246363.ref010","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1472-6882-10-7","article-title":"Laxative activities of Mareya micrantha (Benth.) M\u00fcll. Arg. (Euphorbiaceae) leaf aqueous extract in rats","volume":"10","author":"S Meite","year":"2010","journal-title":"BMC Complement Altern Med"},{"key":"pone.0246363.ref011","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/14786411003754264","article-title":"Anti-inflammatory, laxative and intestinal motility effects of Senna macranthera leaves","volume":"26","author":"L Guarize","year":"2012","journal-title":"Nat Prod Res"},{"key":"pone.0246363.ref012","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/ptr.3634","article-title":"Gastrointestinal stimulant effect of Urginea indica Kunth. and involvement of muscarinic receptors","volume":"26","author":"S Abbas","year":"2012","journal-title":"Phytother Res"},{"key":"pone.0246363.ref013","doi-asserted-by":"crossref","first-page":"144","DOI":"10.5344\/ajev.1965.16.3.144","article-title":"Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents","volume":"16","author":"VL Singleton","year":"1965","journal-title":"Am J Enol Vitic"},{"key":"pone.0246363.ref014","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0308-8146(98)00102-2","article-title":"The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals","volume":"64","author":"J Zhishen","year":"1999","journal-title":"Food Chem"},{"key":"pone.0246363.ref015","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1021\/jf60228a047","article-title":"Tannin content of cowpeas, chick peas, pigeon peas, and mung beans","volume":"28","author":"ML Price","year":"1980","journal-title":"J Agric Food Chem"},{"key":"pone.0246363.ref016","first-page":"24","article-title":"Determination of crude saponin and total flavonoids content in guar meal","volume":"1","author":"SM Hassan","year":"2013","journal-title":"Adv Med Plant Res"},{"key":"pone.0246363.ref017","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3892\/mmr.2016.5983","article-title":"Effects of five candidate laxatives derived from Liriope platyphylla on the 5-HT receptor signaling pathway in three cell types present in the transverse colon","volume":"15","author":"JE Kim","year":"2017","journal-title":"Mol Med Rep"},{"key":"pone.0246363.ref018","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.3892\/etm.2014.2030","article-title":"Laxative effects of fermented rice extract in rats with loperamide-induced constipation","volume":"8","author":"JS Choi","year":"2014","journal-title":"Exp Ther Med"},{"key":"pone.0246363.ref019","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"key":"pone.0246363.ref020","first-page":"495","article-title":"Role of antioxidants in prevention of diseases","volume":"4","author":"K Rani","year":"2017","journal-title":"J Appl Biotechnol Bioeng"},{"key":"pone.0246363.ref021","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF00046166","article-title":"Critical light conditions for young Ecklonia cava and Eisenia bicyclis with reference to photosynthesis","volume":"151","author":"M Maegawa","year":"1987","journal-title":"Hydrobiologia"},{"key":"pone.0246363.ref022","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/j.biortech.2004.07.013","article-title":"Antioxidant activities of enzymatic extracts from brown seaweeds","volume":"96","author":"SJ Heo","year":"2005","journal-title":"Biores Technol"},{"key":"pone.0246363.ref023","doi-asserted-by":"crossref","first-page":"6295","DOI":"10.1016\/j.febslet.2005.10.008","article-title":"Eckol isolated from Ecklonia cava attenuates oxidative stress induced cell damage in lung fibroblast cells","volume":"579","author":"KA Kang","year":"2005","journal-title":"FEBS Lett"},{"key":"pone.0246363.ref024","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00217-006-0510-y","article-title":"Antioxidant activities of phlorotannins purified from Ecklonia cava on free radical scavenging using ESR and H2O2-mediated DNA damage","volume":"226","author":"GN Ahn","year":"2007","journal-title":"Eur Food Res Technol"},{"key":"pone.0246363.ref025","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.bmc.2009.01.031","article-title":"Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava","volume":"17","author":"Y Li","year":"2009","journal-title":"Bioorg Med Chem"},{"key":"pone.0246363.ref026","doi-asserted-by":"crossref","first-page":"7921","DOI":"10.1016\/j.bmc.2008.07.078","article-title":"Anti-HIV-1 activity of phloroglucinol derivative, 6,60-bieckol, from Ecklonia cava","volume":"16","author":"M Artan","year":"2008","journal-title":"Bioorg Med Chem"},{"key":"pone.0246363.ref027","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.fct.2009.04.013","article-title":"Induction of apoptosis by phloroglucinol derivative from Ecklonia cava in MCF-7 human breast cancer cells","volume":"47","author":"CS Kong","year":"2009","journal-title":"Food Chem Toxicol"},{"key":"pone.0246363.ref028","first-page":"134","article-title":"Screening for Angiotensin 1-converting enzyme inhibitory activity of Ecklonia cava","volume":"10","author":"Y Athukorala","year":"2005","journal-title":"J Food Sci Nutr"},{"key":"pone.0246363.ref029","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.fct.2008.11.041","article-title":"Ecklonia cava ethanolic extracts inhibit lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV2","volume":"47","author":"WK Jung","year":"2009","journal-title":"Food Chem Toxicol"},{"key":"pone.0246363.ref030","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1002\/jsfa.3623","article-title":"\u03b1\u2013Glycosidase and \u03b1\u2013amylase inhibitory activities of phloroglucinal derivatives from edible marine brown alga, Ecklonia cava","volume":"89","author":"SH Lee","year":"2009","journal-title":"J Sci Food Agric"},{"key":"pone.0246363.ref031","doi-asserted-by":"crossref","first-page":"15638","DOI":"10.3390\/molecules191015638","article-title":"Eckol enhances heme oxygenase-1 expression through activation of Nrf2\/JNK pathway in HepG2 cells","volume":"19","author":"YJ Jun","year":"2014","journal-title":"Molecules"},{"key":"pone.0246363.ref032","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1016\/j.fct.2012.03.082","article-title":"Vascular barrier protective effects of phlorotannins on HMGB1-mediated proinflammatory responses in vitro and in vivo","volume":"50","author":"TH Kim","year":"2012","journal-title":"Food Chem Toxicol"},{"key":"pone.0246363.ref033","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1111\/jphp.12241","article-title":"Protective effect of the edible brown alga Ecklonia stolonifera on doxorubicin-induced hepatotoxicity in primary rat hepatocytes","volume":"66","author":"HA Jung","year":"2014","journal-title":"J Pharm Pharmacol"},{"key":"pone.0246363.ref034","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.foodres.2012.11.017","article-title":"Acetylcholinesterase inhibitory activity of phlorotannins isolated from the brown alga, Ecklonia maxima (Osbeck) Papenfuss","volume":"54","author":"RR Kannan","year":"2013","journal-title":"Food Res Int"},{"key":"pone.0246363.ref035","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3892\/ijmm.2017.2869","article-title":"Enzyme-treated Ecklonia cava extract inhibits adipogenesis through the downregulation of C\/EBP\u03b1 in 3T3-L1 adipocytes","volume":"39","author":"IH Kim","year":"2017","journal-title":"Int J Mol Med"},{"key":"pone.0246363.ref036","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1111\/j.1444-2906.2006.01288.x","article-title":"Angiotensin-converting enzyme I inhibitory activity of phlorotannins from Ecklonia stolonifera","volume":"72","author":"HA Jung","year":"2006","journal-title":"Fish Sci"},{"key":"pone.0246363.ref037","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3390\/md17060361","article-title":"Characterizing eckol as a therapeutic aid: A systematic review","volume":"17","author":"B Manandhar","year":"2019","journal-title":"Mar Drugs"},{"key":"pone.0246363.ref038","first-page":"341","article-title":"Kim, HT, Lee KW. Antioxidant effect of enzymatic hydrolyzate from a kelp","volume":"18","author":"SJ Heo","year":"2003","journal-title":"Ecklonia cava. Algae"},{"key":"pone.0246363.ref039","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1177\/1082013206062422","article-title":"Antioxidant potential of Ecklonia cavaon reactive oxygen species scavenging, metal chelating, reducing power and lipid peroxidation inhibition","volume":"12","author":"M Senevirathne","year":"2006","journal-title":"Food Sci Technol Int"},{"key":"pone.0246363.ref040","doi-asserted-by":"crossref","first-page":"495","DOI":"10.4162\/nrp.2011.5.6.495","article-title":"Evaluation of antioxidant properties of a new compound, pyrogallol-phloroglucinol -6,6\u2019-bieckol isolated from brown algae, Ecklonia cava","volume":"5","author":"SM Kang","year":"2011","journal-title":"Nutr Res Pract"},{"key":"pone.0246363.ref041","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4014\/jmb.1710.10043","article-title":"Protective effect of fucoidan extract from Ecklonia cava on hydrogen peroxide-induced neurotoxicity","volume":"28","author":"SK Park","year":"2018","journal-title":"J Microbiol Biotechnol"},{"key":"pone.0246363.ref042","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/1471-230X-10-95","article-title":"The effect of Aloe ferox Mill. in the treatment of loperamide-induced constipation in Wistar rats","volume":"10","author":"OA Wintola","year":"2010","journal-title":"BMC Gastroenterol"},{"key":"pone.0246363.ref043","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.fct.2011.12.001","article-title":"Effects of Ficus carica paste on loperamide-induced constipation in rats","volume":"50","author":"HY Lee","year":"2012","journal-title":"Food Chem Toxicol"},{"key":"pone.0246363.ref044","first-page":"257","article-title":"Chelating of Fe(II), Zn(II) and Cu(II) by tannin fractions separated from hazelnuts, walnuts and almonds","volume":"39","author":"M Karamac","year":"2006","journal-title":"Bromat Chem Toksykol"},{"key":"pone.0246363.ref045","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.jep.2011.01.047","article-title":"Prokinetic and laxative activities of Lepidium sativum seed extract with species and tissue selective gut stimulatory actions","volume":"134","author":"N Rehman","year":"2011","journal-title":"J Ethnopharmacol"},{"key":"pone.0246363.ref046","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1472-6882-12-16","article-title":"Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora","volume":"12","author":"N Rehman","year":"2012","journal-title":"BMC Complement Altern Med"},{"key":"pone.0246363.ref047","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/ptr.4821","article-title":"Studies on prokinetic, laxative and spasmodic activities of Phyllanthus emblica in experimental animals","volume":"27","author":"MH Mehmood","year":"2013","journal-title":"Phytother Res"},{"key":"pone.0246363.ref048","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1472-6882-13-70","article-title":"Prokinetic and laxative effects of the crude methanolic extract of Viola betonicifolia whole plant in rodents","volume":"13","author":"N Muhammad","year":"2013","journal-title":"BMC Complement Altern Med"},{"key":"pone.0246363.ref049","first-page":"185","article-title":"Spicatoside A in red Liriope platyphylla displays a laxative effect in a constipation rat model via regulating mAChRs and ER stress signaling","volume":"43","author":"JE Kim","year":"2019","journal-title":"Int J Mol Med"},{"key":"pone.0246363.ref050","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1089\/jmf.2018.4234","article-title":"Synergic laxative effects of an herbal mixture of Liriope platyphylla, Glycyrrhiza uralensis, and Cinnamomum cassia in loperamide-induced constipation of Sprague Dawley rats","volume":"22","author":"JE Kim","year":"2019","journal-title":"J Med Food"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T22:10:07Z","timestamp":1697926207000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246363"}},"subtitle":[],"editor":[{"given":"Saikat","family":"Dewanjee","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0246363","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]}}}