{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:52:13Z","timestamp":1787838733012,"version":"build-2784847793"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2020,1]]},"DOI":"10.1016\/j.fct.2019.111044","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T12:04:08Z","timestamp":1575893048000},"page":"111044","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"special_numbering":"C","title":["Hemistepsin A alleviates liver fibrosis by inducing apoptosis of activated hepatic stellate cells via inhibition of nuclear factor-\u03baB and Akt"],"prefix":"10.1016","volume":"135","author":[{"given":"Jae Kwang","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nu Ri","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Mi","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hwan","family":"Jegal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yun","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Hye","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Ok","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doyeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Hwa","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Rok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung A","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae Kwang","family":"Ku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-0608","authenticated-orcid":false,"given":"Il Je","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-0764","authenticated-orcid":false,"given":"Sang Chan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fct.2019.111044_bib1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/hep.21036","article-title":"Proteasome inhibition induces hepatic stellate cell apoptosis","volume":"43","author":"Anan","year":"2006","journal-title":"Hepatology"},{"key":"10.1016\/j.fct.2019.111044_bib2","doi-asserted-by":"crossref","first-page":"55633","DOI":"10.1074\/jbc.M409825200","volume":"31","author":"Buss","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2019.111044_bib3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.jhep.2014.06.007","article-title":"Protective role of HO-1 and carbon monoxide in ethanol-induced hepatocyte cell death and liver injury in mice","volume":"61","author":"Bakhautdin","year":"2014","journal-title":"J. Hepatol."},{"key":"10.1016\/j.fct.2019.111044_bib4","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.3390\/ijms20174133","article-title":"A cell's fate: an overview of the molecular biology and genetics of apoptosis","volume":"20","author":"Cavalcante","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.fct.2019.111044_bib5","doi-asserted-by":"crossref","first-page":"12780","DOI":"10.3390\/ijms140612780","article-title":"Sesquiterpenoids lactones: benefits to plants and people","volume":"19","author":"Chadwick","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.fct.2019.111044_bib6","first-page":"1357","article-title":"Targeting CAND1 promotes caspase-8\/RIP1-dependent apoptosis in liver cancer cells","volume":"10","author":"Che","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"10.1016\/j.fct.2019.111044_bib7","doi-asserted-by":"crossref","first-page":"7966","DOI":"10.1128\/MCB.25.18.7966-7975.2005","article-title":"NF-\u03baB RelA phosphorylation regulates RelA acetylation","volume":"25","author":"Chen","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.fct.2019.111044_bib8","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/iub.1478","article-title":"Dihydroartemisinin prevents liver fibrosis in bile duct ligated rats by inducing hepatic stellate cell apoptosis through modulating the PI3K\/Akt pathway","volume":"68","author":"Chen","year":"2016","journal-title":"IUBMB Life"},{"key":"10.1016\/j.fct.2019.111044_bib9","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1002\/hep.23931","article-title":"E-cadherin antagonizes transforming growth factor \u03b21 gene induction in hepatic stellate cells by inhibiting RhoA-dependent Smad3 phosphorylation","volume":"52","author":"Cho","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.fct.2019.111044_bib10","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1002\/j.1460-2075.1987.tb02449.x","article-title":"Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor","volume":"6","author":"Edwards","year":"1987","journal-title":"EMBO J."},{"key":"10.1016\/j.fct.2019.111044_bib11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1006\/smim.2001.0333","article-title":"The phagocytosis of apoptotic cells","volume":"13","author":"Fadok","year":"2001","journal-title":"Semin. Immunol."},{"key":"10.1016\/j.fct.2019.111044_bib12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver","volume":"88","author":"Friedman","year":"2008","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.fct.2019.111044_bib13","doi-asserted-by":"crossref","first-page":"39713","DOI":"10.1074\/jbc.M101985200","article-title":"Cysteine 38 in p65\/NF-\u03baB plays a crucial role in DNA binding inhibition by sesquiterpene lactones","volume":"276","author":"Garc\u00eda-Pi\u00f1eres","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2019.111044_bib14","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","article-title":"Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation","volume":"119","author":"Gavrieli","year":"1992","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.fct.2019.111044_bib15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic stellate cell as key target in liver fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.fct.2019.111044_bib16","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1055\/s-2006-960863","article-title":"Hemistepsins with cytotoxic activity from Hemisteptia lyrata","volume":"65","author":"Jang","year":"1999","journal-title":"Planta Med."},{"key":"10.1016\/j.fct.2019.111044_bib17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jhep.2009.03.024","article-title":"Apoptotic body engulfment by hepatic stellate cells promotes their survival by the JAK\/STAT and Akt\/NF-\u03baB-dependent pathways","volume":"51","author":"Jiang","year":"2009","journal-title":"J. Hepatol."},{"key":"10.1016\/j.fct.2019.111044_bib18","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3858\/emm.2012.44.7.051","article-title":"Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic effects in an in vivo rat model","volume":"44","author":"Kim","year":"2012","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.fct.2019.111044_bib19","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.fct.2017.11.014","article-title":"Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-\u03baB and activation of nuclear factor erythroid 2-related factor 2","volume":"111","author":"Kim","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2019.111044_bib20","series-title":"Wild Flowers and Resources Plants in Korea","author":"Kim","year":"2008"},{"key":"10.1016\/j.fct.2019.111044_bib21","first-page":"74","article-title":"Antifungal activities of Hemistepsin A and B isolated from Hemistepta lyrata Bunge against dandruff-causing microbes Malassezia obutusa","volume":"28","author":"Lee","year":"2013","journal-title":"Kor. Soc. Biotechnol. Bioeng."},{"key":"10.1016\/j.fct.2019.111044_bib22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.fitote.2014.03.020","article-title":"Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation","volume":"95","author":"Lin","year":"2014","journal-title":"Fitoterapia"},{"key":"10.1016\/j.fct.2019.111044_bib23","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-\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.fct.2019.111044_bib24","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrgastro.2010.213","article-title":"NF-\u03baB in the liver-linking injury, fibrosis and hepatocellular carcinoma","volume":"8","author":"Luedde","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.fct.2019.111044_bib25","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s10753-019-00973-8","article-title":"Umbelliferone ameliorates CCl4-induced liver fibrosis in rats by upregulating PPAR\u03b3 and attenuating oxidative stress, inflammation, and TGF-\u03b21\/Smad3 signaling","volume":"42","author":"Mahmoud","year":"2019","journal-title":"Inflammation"},{"key":"10.1016\/j.fct.2019.111044_bib26","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1084\/jem.182.5.1545","article-title":"Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl","volume":"182","author":"Martin","year":"1995","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.fct.2019.111044_bib27","first-page":"1538","article-title":"Comparison of glial fibrillary acidic protein and desmin staining in normal and CCl4\u2010induced fibrotic rat livers","volume":"23","author":"Niki","year":"1996","journal-title":"Hepatology"},{"key":"10.1016\/j.fct.2019.111044_bib28","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1053\/j.gastro.2004.10.003","article-title":"Inhibition of inhibitor of \u03baB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis","volume":"128","author":"Oakley","year":"2005","journal-title":"Gastroenterology"},{"key":"10.1016\/j.fct.2019.111044_bib29","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1053\/j.gastro.2009.02.081","article-title":"Angiotensin II activates I\u03baB kinase phosphorylation of RelA at Ser536 to promote myofibroblast survival and liver fibrosis","volume":"136","author":"Oakley","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1016\/j.fct.2019.111044_bib30","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.jgr.2017.01.012","article-title":"20S-Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic stellate cell apoptosis through liver kinase B1-AMP-activated protein kinase activation","volume":"41","author":"Park","year":"2017","journal-title":"J. Ginseng Res."},{"key":"10.1016\/j.fct.2019.111044_bib31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.fitote.2019.02.017","article-title":"Antimicrobial guaianolide sesquiterpenoids from leaves of the Saudi Arabian plant Anvillea garcinii","volume":"134","author":"Perveen","year":"2019","journal-title":"Fitoterapia"},{"key":"10.1016\/j.fct.2019.111044_bib32","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1074\/jbc.M212927200","article-title":"The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type I collagen expression","volume":"278","author":"Reif","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2019.111044_bib33","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00109-011-0748-0","article-title":"AMP-activated protein kinase inhibits NF-\u03baB signaling and inflammation: impact on healthspan and lifespan","volume":"89","author":"Salminen","year":"2011","journal-title":"J. Mol. Med."},{"key":"10.1016\/j.fct.2019.111044_bib34","doi-asserted-by":"crossref","first-page":"6247","DOI":"10.1128\/MCB.22.17.6247-6260.2002","article-title":"Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B","volume":"22","author":"Scheid","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.fct.2019.111044_bib35","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/cbic.200400144","article-title":"NF-\u03baB: a multifaceted transcription factor regulated at several levels","volume":"5","author":"Schmitz","year":"2004","journal-title":"Chembiochem"},{"key":"10.1016\/j.fct.2019.111044_bib36","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-\u03b2 signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat. Med."},{"key":"10.1016\/j.fct.2019.111044_bib37","series-title":"Illustrated Book of Herbal Plants in Oriental Medicine","author":"Seo","year":"2011"},{"key":"10.1016\/j.fct.2019.111044_bib38","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00535-017-1404-4","article-title":"Human hepatic stellate cell isolation and characterization","volume":"53","author":"Shang","year":"2018","journal-title":"J. Gastroenterol."},{"key":"10.1016\/j.fct.2019.111044_bib39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00204-014-1448-7","article-title":"The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update","volume":"89","author":"Siddiqui","year":"2015","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.fct.2019.111044_bib40","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1002\/hep.23186","article-title":"Inhibition of phosphatidylinositol 3-kinase signaling in hepatic stellate cells blocks the progression of hepatic fibrosis","volume":"50","author":"Son","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.fct.2019.111044_bib41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.intimp.2017.09.001","article-title":"Anti-inflammatory and antioxidant potential of Guaianolide isolated from Cyathocline purpurea: role of COX-2 inhibition","volume":"52","author":"Tambewagh","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.fct.2019.111044_bib42","first-page":"175","article-title":"Micheliolide inhibits gastric cancer growth in vitro and in vivo via blockade of the IL-6\/STAT3 pathway","volume":"74","author":"Tang","year":"2019","journal-title":"Die Pharmazie"},{"key":"10.1016\/j.fct.2019.111044_bib43","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.fct.2019.111044_bib44","doi-asserted-by":"crossref","first-page":"18069","DOI":"10.1074\/jbc.M610101200","article-title":"Energy depletion inhibits phosphatidylinositol 3-kinase\/Akt signaling and induces apoptosis via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794","volume":"282","author":"Tzatsos","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2019.111044_bib45","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/hep.24701","article-title":"Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via integrin \u03b1V\u03b23 engagement and PI3K\/pAkt\/NF\u03baB signaling","volume":"55","author":"Urtasun","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.fct.2019.111044_bib46","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jhep.2007.12.019","article-title":"NF-\u03baB is a critical regulator of the survival of rodent and human hepatic myofibroblasts","volume":"48","author":"Watson","year":"2008","journal-title":"J. Hepatol."},{"key":"10.1016\/j.fct.2019.111044_bib47","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1053\/gast.2001.27188","article-title":"Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats","volume":"121","author":"Wright","year":"2001","journal-title":"Gastroenterology"},{"key":"10.1016\/j.fct.2019.111044_bib48","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/ars.2018.7559","article-title":"Inhibitory effect of Sestrin 2 on hepatic stellate cell activation and liver fibrosis","volume":"31","author":"Yang","year":"2019","journal-title":"Antioxidants Redox Signal."}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691519308348?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691519308348?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T21:54:24Z","timestamp":1759528464000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691519308348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":48,"alternative-id":["S0278691519308348"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2019.111044","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hemistepsin A alleviates liver fibrosis by inducing apoptosis of activated hepatic stellate cells via inhibition of nuclear factor-\u03baB and Akt","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2019.111044","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"111044"}}