{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:24:33Z","timestamp":1787678673518,"version":"build-2784847793"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,9]],"date-time":"2019-02-09T00:00:00Z","timestamp":1549670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI","award":["17K08476"],"award-info":[{"award-number":["17K08476"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Nonalcoholic steatohepatitis (NASH) progresses from nonalcoholic fatty liver disease (NAFLD); however, efficacious drugs for NASH treatment are lacking. Sodium alginate (SA), a soluble dietary fiber extracted from brown algae, could protect the small intestine from enterobacterial invasion. NASH pathogenesis has been suggested to be associated with enterobacterial invasion, so we examined the effect of SA on methionine- and choline-deficient (MCD) diet-induced steatohepatitis in mice (the most widely-used model of NASH). The mice (n = 31) were divided into three groups (mice fed with regular chow, MCD diet, and MCD diet premixed with 5% SA) for 4 and 8 weeks. The MCD diet increased lipid accumulation and inflammation in the liver, the NAFLD Activity Score and hepatic mRNA expression of tumor necrosis factor-\u03b1 and collagen 1\u03b11, and induced macrophage infiltration. Villus shortening, disruption of zonula occludens-1 localization and depletion of mucus production were observed in the small intestine of the MCD-group mice. SA administration improved lipid accumulation and inflammation in the liver, and impaired barrier function in the small intestine. Collectively, these results suggest that SA is useful for NASH treatment because it can prevent hepatic inflammation and fatty degeneration by maintaining intestinal barrier function.<\/jats:p>","DOI":"10.3390\/md17020104","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:18:20Z","timestamp":1549941500000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Inhibitory Effects of Sodium Alginate on Hepatic Steatosis in Mice Induced by a Methionine- and Choline-Deficient Diet"],"prefix":"10.3390","volume":"17","author":[{"given":"Shoji","family":"Kawauchi","sequence":"first","affiliation":[{"name":"Education and Research Center for Clinical Pharmacy, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayo","family":"Horibe","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihito","family":"Tanahashi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan"},{"name":"Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeto","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan"},{"name":"Endoscopy Department, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma 630-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneo","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Education and Research Center for Clinical Pharmacy, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-4656","authenticated-orcid":false,"given":"Yoshiyuki","family":"Rikitake","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1002\/hep.23527","article-title":"The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis","volume":"51","author":"Ascha","year":"2010","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.24001","article-title":"Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis","volume":"52","author":"Tilg","year":"2010","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbalip.2009.10.007","article-title":"Fatty liver and lipotoxicity","volume":"1801","author":"Trauner","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0140-6736(14)61933-4","article-title":"Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): A multicentre, randomised, placebo-controlled trial","volume":"385","author":"Loomba","year":"2015","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1136\/gut.48.2.206","article-title":"The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis","volume":"48","author":"Wigg","year":"2001","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jcmgh.2015.01.001","article-title":"Hepatic injury in nonalcoholic steatohepatitis contributes to altered intestinal permeability","volume":"1","author":"Luther","year":"2015","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000353192","article-title":"Effect of sodium alginate on dextran sulfate sodium- and 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis in mice","volume":"92","author":"Yamamoto","year":"2013","journal-title":"Pharmacology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.1365-2036.1998.00283.x","article-title":"Randomized, multicentre comparison of sodium alginate and cisapride in the symptomatic treatment of uncomplicated gastro-oesophageal reflux","volume":"12","author":"Poynard","year":"1998","journal-title":"Aliment Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.7150\/ijms.16232","article-title":"Preventative effects of sodium alginate on indomethacin-induced small-intestinal injury in mice","volume":"13","author":"Horibe","year":"2016","journal-title":"Int. J. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1053\/jhep.2003.50048","article-title":"Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease","volume":"37","author":"Li","year":"2003","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1006\/scdb.2000.0178","article-title":"MAGUK proteins: Structure and role in the tight junction","volume":"11","author":"Betanzos","year":"2000","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1590\/S0004-28032011000100015","article-title":"Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis","volume":"48","author":"Marcolin","year":"2011","journal-title":"Arq. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6866","DOI":"10.3390\/md13116866","article-title":"Polyphenol-rich fraction of ecklonia cava improves nonalcoholic fatty liver disease in high fat diet-fed mice","volume":"13","author":"Park","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gabbia, D., Dall\u2019Acqua, S., Di Gangi, I.M., Bogialli, S., Caputi, V., Albertoni, L., Marsilio, I., Paccagnella, N., Carrara, M., and Giron, M.C. (2017). The phytocomplex from fucus vesiculosus and ascophyllum nodosum controls postprandial plasma glucose levels: An in vitro and in vivo study in a mouse model of NASH. Mar. Drugs, 15.","DOI":"10.3390\/md15020041"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Machado, M.V., Michelotti, G.A., Xie, G., Almeida Pereira, T., Boursier, J., Bohnic, B., Guy, C.D., and Diehl, A.M. (2015). Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132315"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1136\/gut.2005.071118","article-title":"Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice","volume":"55","author":"Tomita","year":"2006","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1053\/gast.2000.19267","article-title":"Increased gastrointestinal ethanol production in obese mice: Implications for fatty liver disease pathogenesis","volume":"119","author":"Cope","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ritze, Y., B\u00e1rdos, G., Claus, A., Ehrmann, V., Bergheim, I., Schwiertz, A., and Bischoff, S.C. (2014). Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0080169"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Endo, H., Niioka, M., Kobayashi, N., Tanaka, M., and Watanabe, T. (2013). Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: New insight into the probiotics for the gut-liver axis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063388"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1073\/pnas.94.6.2557","article-title":"Obesity increases sensitivity to endotoxin liver injury: Implications for the pathogenesis of steatohepatitis","volume":"94","author":"Yang","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1124\/jpet.112.201137","article-title":"Puerarin ameliorates experimental alcoholic liver injury by inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression","volume":"344","author":"Peng","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/2191172a0","article-title":"Absorption by the rat of alginate labelled with carbon-14","volume":"219","author":"Humphreys","year":"1968","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1248\/yakushi1947.101.5_452","article-title":"Pharmacological studies of sodium alginate. I. Protective effect of sodium alginate on mucous membranes of upper-gastrointestinal tract","volume":"101","author":"Daigo","year":"1981","journal-title":"Yakugaku Zasshi"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.3748\/wjg.v20.i10.2641","article-title":"Sodium alginate ameliorates indomethacin-induced gastrointestinal mucosal injury via inhibiting translocation in rats","volume":"20","author":"Yamamoto","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1111\/1440-1681.12792","article-title":"Probiotic Bifidobacterium bifidum G9-1 attenuates 5-fluorouracil-induced intestinal mucositis in mice. via suppression of dysbiosis-related secondary inflammatory responses","volume":"44","author":"Kato","year":"2017","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_27","first-page":"2954","article-title":"TNF-alpha drives remodeling of blood vessels and lymphatics in sustained airway inflammation in mice","volume":"119","author":"Baluk","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/cyto.1998.0426","article-title":"Quantification of murine cytokine mRNAs using real time quantitative reverse transcriptase PCR","volume":"11","author":"Overbergh","year":"1999","journal-title":"Cytokine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1124\/jpet.108.144600","article-title":"Farnesoid X receptor deficiency induces nonalcoholic steatohepatitis in low-density lipoprotein receptor-knockout mice fed a high-fat diet","volume":"328","author":"Kong","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/2\/104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:30:52Z","timestamp":1760185852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/2\/104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,9]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["md17020104"],"URL":"https:\/\/doi.org\/10.3390\/md17020104","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,9]]}}}