{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:33:18Z","timestamp":1768343598392,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003718","name":"Korea Institute of Oriental Medicine","doi-asserted-by":"publisher","award":["K17281"],"award-info":[{"award-number":["K17281"]}],"id":[{"id":"10.13039\/501100003718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003718","name":"Korea Institute of Oriental Medicine","doi-asserted-by":"publisher","award":["KSN2021230"],"award-info":[{"award-number":["KSN2021230"]}],"id":[{"id":"10.13039\/501100003718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Forsythia Fruit (FF), the fruit of Forsythia suspensa, has been used since ancient times as an herbal medication in East Asia to treat inflammation, gonorrhea, and pharyngitis. However, the efficacy of FF against liver damage due to inflammation has not been studied. Here, we explored the protective effects of FF in a mouse hepatitis model induced by lipopolysaccharide (LPS)\/D-galactosamine (GalN) treatment. We measured inflammatory cytokine and aminotransferase levels in mouse blood and analyzed the effects of FF on inflammatory gene and protein expression levels in liver tissue. Our results show that FF treatment effectively lowers inflammatory cytokine and serum aminotransferase levels in mice and inhibits the expression of hepatic cytokine mRNA and inflammatory proteins. Furthermore, treatment with FF activated the antioxidant pathway HO-1\/Nrf-2 and suppressed severe histological alteration in the livers of LPS\/D-GalN-treated mice. Further investigation of the effects of FF on inflammatory reactions in LPS-stimulated macrophages showed that pretreatment with FF inhibits inflammatory mediator secretion and activation of inflammatory mechanisms both in a mouse macrophage RAW 264.7 cells and in primary peritoneal macrophages. These results show that FF has potential worth as a candidate for the treatment of fulminant inflammatory reactions and subsequent liver injury.<\/jats:p>","DOI":"10.3390\/nu13082901","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T10:24:17Z","timestamp":1629714257000},"page":"2901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Forsythia Fruit Prevents Fulminant Hepatitis in Mice and Ameliorates Inflammation in Murine Macrophages"],"prefix":"10.3390","volume":"13","author":[{"given":"Yun Hee","family":"Jeong","sequence":"first","affiliation":[{"name":"Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine, 70, Cheomdanro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4959-2436","authenticated-orcid":false,"given":"Youn-Hwan","family":"Hwang","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine, 70, Cheomdanro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9495-3782","authenticated-orcid":false,"given":"Tae In","family":"Kim","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine, 70, Cheomdanro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9889-7770","authenticated-orcid":false,"given":"You-Chang","family":"Oh","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine, 70, Cheomdanro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Yeul","family":"Ma","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine, 70, Cheomdanro, Dong-gu, Daegu 41062, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1055\/s-2008-1040593","article-title":"Fulminant and subfulminant liver failure: Definitions and causes","volume":"6","author":"Bernuau","year":"1986","journal-title":"Semin. Liver Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0140-6736(10)60274-7","article-title":"Acute liver failure","volume":"376","author":"Bernal","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrc1934","article-title":"Hepatocellular carcinoma pathogenesis: From genes to environment","volume":"6","author":"Farazi","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"310","DOI":"10.47102\/annals-acadmedsg.V38N4p322","article-title":"Liver transplantation in Asia: Past, present and future","volume":"38","author":"Ng","year":"2009","journal-title":"Ann. Acad. Med. Singapore"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s12072-010-9219-x","article-title":"The role of lipopolysaccharide\/toll-like receptor 4 signaling in chronic liver diseases","volume":"4","author":"Soares","year":"2010","journal-title":"Hepatol. Int."},{"key":"ref_6","first-page":"53","article-title":"Prevention of galactosamine-induced liver necrosis by uridine","volume":"72","author":"Farber","year":"1973","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.3746\/jkfn.2015.44.10.1422","article-title":"Effect of fermented water extracts from Ligularia fischeri on hepatotoxicity induced by D-galactosamine in rats","volume":"44","author":"Yu","year":"2015","journal-title":"J. Korean Soc. Food Sci. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0016-5085(85)80142-6","article-title":"D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice","volume":"88","author":"Chojkier","year":"1985","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0014-4800(68)90042-7","article-title":"Experimental hepatitis induced by D-galactosamine","volume":"9","author":"Keppler","year":"1968","journal-title":"Exp. Mol. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/0014-4800(70)90075-4","article-title":"Liver restitution after acute galactosamine hepatitis: Autoradiographic and biochemical studies in rats","volume":"12","author":"Lesch","year":"1969","journal-title":"Exp. Mol. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/sj.bjp.0707230","article-title":"Antileukoproteinase protects against hepatic inflammation, but not apoptosis in the response of D-galactosamine-sensitized mice to lipopolysaccharide","volume":"151","author":"Eipel","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","first-page":"400","article-title":"Modulation of superoxide anion generation by manoalide, arachidonic acid and staurosporine in liver infiltrated neutrophils in a rat model of endotoxemia","volume":"267","author":"Mayer","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1007\/s10753-013-9805-x","article-title":"Inhibitions of NF-\u03baB and TNF-\u03b1 result in differential effects in rats with acute on chronic liver failure induced by d-Gal and LPS","volume":"37","author":"Yang","year":"2014","journal-title":"Inflammation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.1074\/jbc.275.9.6259","article-title":"Transcriptional activation of the cyclooxygenase-2 gene in endotoxin-treated RAW 264.7 macrophages","volume":"275","author":"Wadleigh","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.jep.2014.02.029","article-title":"A herbal formula consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos inhibits inflammatory mediators in LPS-stimulated RAW 264.7 macrophages","volume":"153","author":"Cheng","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1006\/excr.1999.4685","article-title":"AP-1: One switch for many signals","volume":"253","author":"Wisdom","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1152\/physrev.00011.2005","article-title":"Heme oxygenase-1\/carbon monoxide: From basic science to therapeutic applications","volume":"86","author":"Ryter","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1023\/A:1015957026924","article-title":"Heme oxygenase\/carbon monoxide signaling pathways: Regulation and functional significance","volume":"234","author":"Ryter","year":"2002","journal-title":"Mol. Cell Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9184769","DOI":"10.1155\/2019\/9184769","article-title":"Hoveniae Semen Seu Fructus Ethanol Extract Exhibits Anti-Inflammatory Activity via MAPK, AP-1, and STAT Signaling Pathways in LPS-Stimulated RAW 264.7 and Mouse Peritoneal Macrophages","volume":"2019","author":"Jeong","year":"2019","journal-title":"Mediators Inflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/j.bmcl.2008.01.115","article-title":"Lignans from the fruits of Forsythia suspensa","volume":"18","author":"Piao","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/jam.14800","article-title":"Antimicrobial effects of three herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) on membrane permeability and apoptosis in Salmonella","volume":"130","author":"Bae","year":"2021","journal-title":"J. Appl. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.jep.2016.07.002","article-title":"Antidiabetic and antihyperlipidemic activities of Forsythia suspensa (Thunb.) Vahl (fruit) in streptozotocin-induced diabetes mice","volume":"192","author":"Zhang","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","first-page":"990","article-title":"Effect of Forsythia Viridissima Extracts on Antioxidative System and Lipid Peroxidation of Liver in Rats Fed High-Cholesterol Diet","volume":"36","author":"Lee","year":"2003","journal-title":"Korean J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.3382\/ps.2008-00023","article-title":"Effects of Forsythia suspensa extract on growth performance, nutrient digestibility, and antioxidant activities in broiler chickens under high ambient temperature","volume":"87","author":"Wang","year":"2008","journal-title":"Poult. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.jpba.2006.09.033","article-title":"Simultaneous determination of 12 major constituents in Forsythia suspensa by high performance liquid chromatography--DAD method","volume":"43","author":"Guo","year":"2007","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_27","first-page":"154","article-title":"Effects of alcohol consumption and fat content in diet on chemical composition and morphology of liver in rat","volume":"21","author":"Chung","year":"1988","journal-title":"Korean J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jep.2016.08.033","article-title":"Cerbera manghas methanol extract exerts anti-inflammatory activity by targeting c-Jun N-terminal kinase in the AP-1 pathway","volume":"193","author":"Yi","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.intimp.2012.08.011","article-title":"Alantolactone suppresses inducible nitric oxide synthase and cyclooxygenase-2 expression by down-regulating NF-kappaB, MAPK and AP-1 via the MyD88 signaling pathway in LPS-activated RAW 264.7 cells","volume":"14","author":"Chun","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1152\/physrev.00028.2011","article-title":"Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update","volume":"92","author":"Kyriakis","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.intimp.2015.03.009","article-title":"Protective effect of forsythiaside A on lipopolysaccharide\/d-galactosamine-induced liver injury","volume":"26","author":"Pan","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113890","DOI":"10.1016\/j.jep.2021.113890","article-title":"Hepatoprotective effect of forsythiaside a against acetaminophen-induced liver injury in zebrafish: Coupling network pharmacology with biochemical pharmacology","volume":"271","author":"Gong","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s11064-015-1731-x","article-title":"Forsythiaside A Exhibits Anti-inflammatory Effects in LPS-Stimulated BV2 Microglia Cells Through Activation of Nrf2\/HO-1 Signaling Pathway","volume":"41","author":"Wang","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1254\/jphs.09234FP","article-title":"Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice","volume":"112","author":"Kim","year":"2010","journal-title":"J. Pharmacol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112361","DOI":"10.1016\/j.jep.2019.112361","article-title":"Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4\/MyD88\/NF-kappaB signaling pathway","volume":"248","author":"Hu","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7964318","DOI":"10.1155\/2018\/7964318","article-title":"Evaluation of the Pharmacokinetics and Hepatoprotective Effects of Phillygenin in Mouse","volume":"2018","author":"Song","year":"2018","journal-title":"Biomed. Res. Int."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/8\/2901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:49:53Z","timestamp":1760165393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/8\/2901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["nu13082901"],"URL":"https:\/\/doi.org\/10.3390\/nu13082901","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]}}}