{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:59:43Z","timestamp":1778741983062,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05292"],"award-info":[{"award-number":["16H05292"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Non-alcoholic steatohepatitis (NASH) is a progressive disease that occurs in the liver. As the number of people with NASH has increased, effective prevention and treatment strategies are needed. Agaricus brasiliensis KA21 (AGA) is a mushroom native to Brazil and is considered a healthy food because of its purported health benefits, including its antioxidant properties. In this study, we focused on the oxidative stress that accompanies the onset of NASH and examined whether AGA can prevent NASH development through its antioxidant activity. We used a mouse model of NASH in which pathogenesis was promoted by dietary induction. Supplementation with AGA attenuated the development of hepatic fibrosis, which is a characteristic feature of late-stage NASH. This effect appeared to be mechanistically linked to an AGA-promoted reduction in hepatic oxidative stress. These results demonstrate a novel role for AGA in NASH prevention.<\/jats:p>","DOI":"10.3390\/foods8110546","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T04:13:08Z","timestamp":1572840788000},"page":"546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Agaricus brasiliensis KA21 May Prevent Diet-Induced Nash Through Its Antioxidant, Anti-Inflammatory, and Anti-Fibrotic Activities in the Liver"],"prefix":"10.3390","volume":"8","author":[{"given":"Anna","family":"Nakamura","sequence":"first","affiliation":[{"name":"Systems Biology Program, Graduate School of Media and Governance, Keio University, Kanagawa 252-0882, Japan"},{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"},{"name":"Department of Environment and Information Studies, Keio University, Kanagawa 252-0882, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Systems Biology Program, Graduate School of Media and Governance, Keio University, Kanagawa 252-0882, Japan"},{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naho","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Systems Biology Program, Graduate School of Media and Governance, Keio University, Kanagawa 252-0882, Japan"},{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sena","family":"Uchida","sequence":"additional","affiliation":[{"name":"Systems Biology Program, Graduate School of Media and Governance, Keio University, Kanagawa 252-0882, Japan"},{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayo","family":"Kumadaki","sequence":"additional","affiliation":[{"name":"Systems Biology Program, Graduate School of Media and Governance, Keio University, Kanagawa 252-0882, Japan"},{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-7111","authenticated-orcid":false,"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Systems Biology Program, Graduate School of Media and Governance, Keio University, Kanagawa 252-0882, Japan"},{"name":"Health Science Laboratory, Keio Research Institute at SFC, Kanagawa 252-0882, Japan"},{"name":"Department of Environment and Information Studies, Keio University, Kanagawa 252-0882, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"ref_1","first-page":"329","article-title":"Antioxidant activity of romanian Agaricus blazei Murrill. and Agaricus bisporus JE. lange mushrooms","volume":"65","author":"Costea","year":"2017","journal-title":"FARMACIA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1590\/S1517-83822011000100024","article-title":"Antioxidant activity of Agaricus brasiliensis basidiocarps on different maturation phases","volume":"42","author":"Umeo","year":"2011","journal-title":"Braz. J. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00394-011-0270-8","article-title":"Pro-inflammatory effects of the mushroom Agaricus blazei and its consequences on atherosclerosis development","volume":"51","author":"Roma","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1089\/jmf.2008.0177","article-title":"Anti-Inflammatory Activity of Aqueous and Alkaline Extracts from Mushrooms (Agaricus blazei Murill)","volume":"12","author":"Padilha","year":"2009","journal-title":"J. Med. Food"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1039\/C7FO01172E","article-title":"The anti-inflammatory effect of Agaricus brasiliensis is partly due to its linoleic acid content","volume":"8","author":"Saiki","year":"2017","journal-title":"Food Funct."},{"key":"ref_6","first-page":"43","article-title":"Mushrooms and cardiovascular disease","volume":"10","author":"Author","year":"2012","journal-title":"Curr. Top. Nutraceutical Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1021\/jf9036672","article-title":"Semipurified Fractions from the Submerged-Culture Broth of Agaricus blazei Murill Reduce Blood Glucose Levels in Streptozotocin-Induced Diabetic Rats","volume":"58","author":"Oh","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.supflu.2012.06.010","article-title":"Supercritical fluid extraction of Agaricus brasiliensis: Antioxidant and antimicrobial activities","volume":"70","author":"Mazzutti","year":"2012","journal-title":"J. Supercrit. Fluids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/oby.20276","article-title":"Dietary supplementation with Agaricus blazei murill extract prevents diet-induced obesity and insulin resistance in rats","volume":"21","author":"Vincent","year":"2013","journal-title":"Obesity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1007\/s00394-016-1217-x","article-title":"Agaricus brasiliensis (sun mushroom) affects the expression of genes related to cholesterol homeostasis","volume":"56","author":"Silva","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1089\/jmf.2013.2934","article-title":"Agaricus brasiliensis KA21 Improves Circulatory Functions in Spontaneously Hypertensive Rats","volume":"17","author":"Tsubone","year":"2014","journal-title":"J. Med. Food"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s10529-005-2225-8","article-title":"Anti-diabetic activity of \u03b2-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei","volume":"27","author":"Kim","year":"2005","journal-title":"Biotechnol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1089\/acm.2006.6054","article-title":"The Mushroom Agaricus Blazei Murill in Combination with Metformin and Gliclazide Improves Insulin Resistance in Type 2 Diabetes: A Randomized, Double-blinded, and Placebo-Controlled Clinical Trial","volume":"13","author":"Hsu","year":"2007","journal-title":"J. Altern. Complement. Med."},{"key":"ref_14","first-page":"157015","article-title":"The Mushroom Agaricus blazei Murill Elicits Medicinal Effects on Tumor, Infection, Allergy, and Inflammation through Its Modulation of Innate Immunity and Amelioration of Th1\/Th2 Imbalance and Inflammation","volume":"2011","author":"Hetland","year":"2011","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1139\/Y09-111","article-title":"Effects of Agaricus brasiliensis mushroom in Walker-256 tumor-bearing rats","volume":"88","author":"Jumes","year":"2010","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1365-3083.2008.02156.x","article-title":"Effects of the Medicinal Mushroom Agaricus blazei Murill on Immunity, Infection and Cancer","volume":"68","author":"Hetland","year":"2008","journal-title":"Scand. J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"192381","DOI":"10.1155\/2011\/192381","article-title":"Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission","volume":"2011","author":"Ohno","year":"2011","journal-title":"Evid. Based. Complement. Alternat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1093\/jjco\/hyl108","article-title":"An Alternative Medicine, Agaricus blazei, May Have Induced Severe Hepatic Dysfunction in Cancer Patients","volume":"36","author":"Mukai","year":"2006","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/ecam\/nem007","article-title":"The Medicinal Mushroom Agaricus blazei Murrill: Review of Literature and Pharmaco-Toxicological Problems","volume":"5","author":"Firenzuoli","year":"2008","journal-title":"Evid. Based. Complement. Alternat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1365-3083.2011.02656.x","article-title":"Agaricus blazei Murrill and Inflammatory Mediators in Elderly Women: A Randomized Clinical Trial","volume":"75","author":"Lima","year":"2012","journal-title":"Scand. J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s002620050473","article-title":"Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis","volume":"46","author":"Fujimiya","year":"1998","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_22","first-page":"355","article-title":"Crude Extracts of Agaricus brasiliensis Induce Apoptosis in Human Oral Cancer CAL 27 Cells through a Mitochondria-dependent Pathway","volume":"25","author":"Fan","year":"2011","journal-title":"In Vivo (Brooklyn)."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jhep.2018.03.011","article-title":"A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer","volume":"69","author":"Tsuchida","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/ecam\/nem016","article-title":"Immunomodulating Activity of Agaricus brasiliensis KA21 in Mice and in Human Volunteers","volume":"5","author":"Liu","year":"2008","journal-title":"Evid. Based. Complement. Alternat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"842619","DOI":"10.1155\/2013\/842619","article-title":"The Medicinal Values of Culinary-Medicinal Royal Sun Mushroom (Agaricus blazei Murrill)","volume":"2013","author":"Wang","year":"2013","journal-title":"Evid. Based. Complement. Alternat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/liv.13302","article-title":"Therapies in non-alcoholic steatohepatitis (NASH)","volume":"37","author":"Oseini","year":"2017","journal-title":"Liver Int."},{"key":"ref_27","unstructured":"(2019, October 28). NASH prevalence: Key figures | The NASH Education ProgramTM. Available online: https:\/\/www.the-nash-education-program.com\/what-is-nash\/key-figures\/."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/hep4.1033","article-title":"NASH-related cirrhosis: An occult liver disease burden","volume":"1","author":"Arrese","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000446379","article-title":"NASH Cirrhosis\u2014the New Burden in Liver Transplantation: How Should It Be Managed?","volume":"32","author":"Canbay","year":"2016","journal-title":"Visc. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1002\/hep.20973","article-title":"Nonalcoholic fatty liver disease: From steatosis to cirrhosis","volume":"43","author":"Farrell","year":"2006","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41575-018-0009-6","article-title":"Triggering and resolution of inflammation in NASH","volume":"15","author":"Schuster","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_32","first-page":"57","article-title":"Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis","volume":"34","author":"Koruk","year":"2004","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ore, A., Akinloye, O.A., Ore, A., and Akinloye, O.A. (2019). Oxidative Stress and Antioxidant Biomarkers in Clinical and Experimental Models of Non-Alcoholic Fatty Liver Disease. Medicina (B. Aires)., 55.","DOI":"10.3390\/medicina55020026"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9547613","DOI":"10.1155\/2018\/9547613","article-title":"Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease","volume":"2018","author":"Masarone","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"805841","DOI":"10.1155\/2014\/805841","article-title":"Mushrooms: A potential natural source of anti-inflammatory compounds for medical applications","volume":"2014","author":"Elsayed","year":"2014","journal-title":"Mediators Inflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5009\/gnl.2012.6.2.149","article-title":"NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications","volume":"6","author":"Farrell","year":"2012","journal-title":"Gut Liver"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1586\/egh.11.21","article-title":"Inflammation in Nonalcoholic Steatohepatitis","volume":"5","author":"Harmon","year":"2011","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/hep.29495","article-title":"Transmembrane BAX Inhibitor motif-containing 1, a novel anti-inflammatory approach for nonalcoholic steatohepatitis treatment","volume":"67","author":"Wree","year":"2018","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22251","DOI":"10.1038\/srep22251","article-title":"Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis","volume":"6","author":"Kessoku","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","first-page":"947575","article-title":"Antioxidant therapy in nonalcoholic steatohepatitis","volume":"2012","author":"Bhat","year":"2012","journal-title":"Hepat. Res. Treat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1223-P","DOI":"10.2337\/db18-1223-P","article-title":"Role of Vitamin E for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Patients with T2DM\u2014A Randomized, Controlled Trial","volume":"67","author":"Bril","year":"2018","journal-title":"Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1056\/NEJMoa0907929","article-title":"Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis","volume":"362","author":"Sanyal","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17192","DOI":"10.1038\/srep17192","article-title":"Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E","volume":"5","author":"Ni","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8656","DOI":"10.1074\/jbc.RA117.001653","article-title":"Hepatocyte nuclear receptor SHP suppresses inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis","volume":"293","author":"Zou","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature04330","article-title":"Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation","volume":"439","author":"Watanabe","year":"2006","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.nut.2006.09.004","article-title":"Dietary habits and nutrient intake in non-alcoholic steatohepatitis","volume":"23","author":"Toshimitsu","year":"2007","journal-title":"Nutrition"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/8\/11\/546\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:31:39Z","timestamp":1760189499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/8\/11\/546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,4]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["foods8110546"],"URL":"https:\/\/doi.org\/10.3390\/foods8110546","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,4]]}}}