{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T01:40:33Z","timestamp":1776390033727,"version":"3.51.2"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T00:00:00Z","timestamp":1329782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to evaluate the antioxidant mechanisms of red ginseng essential oil (REO) in cells as well as in an animal model. REO was prepared by a supercritical CO2 extraction of waste-products generated after hot water extraction of red ginseng. In HepG2 cells, REO diminished the H2O2-mediated oxidative stress and also restored both the activity and expression of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Administration of REO inhibited the phosphorylation of upstream mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38. In mice, the CCl4-mediated elevation of serum aspartate transaminase and alanine transaminase as well as the induction of hepatic lipid peroxidation were decreased by REO administration. REO treatments also resulted in up-regulation of the antioxidant enzyme expression in the liver. Moreover, increased phosphorylations of MAPKs were inhibited after REO administration. Overall, REO seems to protect the liver from oxidative stress through the activation and induction of antioxidant enzymes via inhibition of MAPKs pathways.<\/jats:p>","DOI":"10.3390\/ijms13022314","type":"journal-article","created":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T11:10:48Z","timestamp":1329822648000},"page":"2314-2330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Antioxidant and Hepatoprotective Effects of the Red Ginseng Essential Oil in H2O2-Treated HepG2 Cells and CCl4-Treated Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Min-Ji","family":"Bak","sequence":"first","affiliation":[{"name":"Institute for Phytochemical-Drug Interactions, Department of Food & Life Sciences, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mira","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Food Science & Nutrition, Dong-A University, Busan 604-714, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo-Sik","family":"Jeong","sequence":"additional","affiliation":[{"name":"Institute for Phytochemical-Drug Interactions, Department of Food & Life Sciences, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/biof.5520270101","article-title":"Free radicals in biology and medicine: from inflammation to biotechnology","volume":"27","author":"Aruoma","year":"2006","journal-title":"Biofactors"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1159\/000329383","article-title":"A role for oxidative stress","volume":"174","author":"Heyman","year":"2011","journal-title":"Contrib. Nephrol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3909\/ricm0555","article-title":"The role of oxidative stress in the metabolic syndrome","volume":"12","author":"McCullough","year":"2011","journal-title":"Rev. Cardiovasc. Med"},{"key":"ref_4","first-page":"304","article-title":"Reactive oxygen species in health and disease","volume":"13","author":"Datta","year":"2000","journal-title":"Natl. Med. J. India"},{"key":"ref_5","first-page":"447","article-title":"Nutritional antioxidants: their role in disease prevention","volume":"108","author":"Winterbourn","year":"1995","journal-title":"N. Z. Med. J"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2005.12.009","article-title":"Free radicals, metals and antioxidants in oxidative stress-induced cancer","volume":"160","author":"Valko","year":"2006","journal-title":"Chem. Biol. Interact"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1089\/jmf.2010.1213","article-title":"Stimulation of Activity and Expression of Antioxidant Enzymes by Solvent Fractions and Isolated Compound from Cedrela sinensis Leaves in HepG2 Cells","volume":"14","author":"Bak","year":"2011","journal-title":"J. Med. Food"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1080\/14786419.2010.533669","article-title":"Evaluation of renal protective effects of the green-tea (EGCG) and red grape resveratrol: Role of oxidative stress and inflammatory cytokines","volume":"25","author":"Salem","year":"2011","journal-title":"Nat. Prod. Res"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.fct.2010.11.035","article-title":"Hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats","volume":"49","author":"Yurt","year":"2011","journal-title":"Food Chem. Toxicol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/biof.5520270121","article-title":"Low molecular proanthocyanidin dietary biofactor Oligonol: Its modulation of oxidative stress, bioefficacy, neuroprotection, food application and chemoprevention potentials","volume":"27","author":"Aruoma","year":"2006","journal-title":"Biofactors"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/j.1365-2125.2008.03236.x","article-title":"Red ginseng for treating erectile dysfunction: a systematic review","volume":"66","author":"Jang","year":"2008","journal-title":"Br. J. Clin. Pharmacol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/ptr.2606","article-title":"Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways","volume":"23","author":"Hwang","year":"2009","journal-title":"Phytother. Res"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.urology.2004.10.038","article-title":"Free radical-scavenging activity of Korean red ginseng for erectile dysfunction in non-insulin-dependent diabetes mellitus rats","volume":"65","author":"Ryu","year":"2005","journal-title":"Urology"},{"key":"ref_14","first-page":"543","article-title":"Protective effects of Asian dietary items on cancers\u2014soy and ginseng","volume":"9","author":"Kim","year":"2008","journal-title":"Asian Pac. J. Cancer Prev"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1089\/jmf.2008.1390","article-title":"Red ginseng root extract mixed with Torilus fructus and Corni fructus improves facial wrinkles and increases type I procollagen synthesis in human skin: a randomized, double-blind, placebo-controlled study","volume":"12","author":"Cho","year":"2009","journal-title":"J. Med. Food"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/ptr.2561","article-title":"Comparison of the antiobesity effects of the protopanaxadiol- and protopanaxatriol-type saponins of red ginseng","volume":"23","author":"Kim","year":"2009","journal-title":"Phytother. Res"},{"key":"ref_17","first-page":"1179","article-title":"Chemical composition and antioxidant activities of the essential oil from Tornabenea bischoffii (Apiaceae)","volume":"6","author":"Ortet","year":"2011","journal-title":"Nat. Prod. Commun"},{"key":"ref_18","first-page":"221","article-title":"In vivo antioxidant activity of Zataria multiflora Boiss essential oil","volume":"24","author":"Sharififar","year":"2011","journal-title":"Pak. J. Pharm. Sci"},{"key":"ref_19","first-page":"1193","article-title":"Neolitsea aciculata essential oil inhibits drug-resistant skin pathogen growth and Propionibacterium acnes-induced inflammatory effects of human monocyte leukemia","volume":"6","author":"Kim","year":"2011","journal-title":"Nat. Prod. Commun"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"709","DOI":"10.3109\/13880209.2010.541924","article-title":"Antioxidant activity of Citrus limon essential oil in mouse hippocampus","volume":"49","author":"Campelo","year":"2011","journal-title":"Pharm. Biol"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1089\/jmf.2010.1313","article-title":"Antiobesity effect of oil extract of ginseng","volume":"14","author":"Kim","year":"2011","journal-title":"J. Med. Food"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/jmf.2009.1142","article-title":"A lipid-soluble red ginseng extract inhibits the growth of human lung tumor xenografts in nude mice","volume":"13","author":"Lee","year":"2010","journal-title":"J. Med. Food"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/BF01907940","article-title":"The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart","volume":"77","author":"Meerson","year":"1982","journal-title":"Basic Res. Cardiol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S1050-1738(97)00133-3","article-title":"Reactive oxygen species as mediators of signal transduction in cardiovascular disease","volume":"8","author":"Abe","year":"1998","journal-title":"Trends Cardiovasc. Med"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1089\/ars.2010.3363","article-title":"Mitochondrial ROS generation and its regulation: mechanisms involved in H(2)O(2) signaling","volume":"14","author":"Rigoulet","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1749-6632.2009.04918.x","article-title":"Antioxidant and apoptotic effects of korean white ginseng extracted with the same ratio of protopanaxadiol and protopanaxatriol saponins in human hepatoma HepG2 cells","volume":"1171","author":"Lee","year":"2009","journal-title":"Ann. NY Acad. Sci"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S1734-1140(11)70584-9","article-title":"No protective effect of curcumin on hydrogen peroxide-induced cytotoxicity in HepG2 cells","volume":"63","author":"Chen","year":"2011","journal-title":"Pharmacol. Rep"},{"key":"ref_28","first-page":"1213","article-title":"Oxidants, antioxidants and carcinogenesis","volume":"40","author":"Ray","year":"2002","journal-title":"Indian J. Exp. Biol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1248\/bpb.34.1072","article-title":"Rb1 protects endothelial cells from hydrogen peroxide-induced cell senescence by modulating redox status","volume":"34","author":"Liu","year":"2011","journal-title":"Biol. Pharm. Bull"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.jep.2007.03.010","article-title":"Neuroprotective effect of a ginseng (Panax ginseng) root extract on astrocytes primary culture","volume":"112","author":"Naval","year":"2007","journal-title":"J. Ethnopharmacol"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/alcalc\/agq034","article-title":"Saponins from Panax japonicus protect against alcohol-induced hepatic injury in mice by up-regulating the expression of GPX3, SOD1 and SOD3","volume":"45","author":"Li","year":"2010","journal-title":"Alcohol Alcohol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.tox.2009.10.010","article-title":"Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention","volume":"278","author":"Neergheen","year":"2011","journal-title":"Toxicology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/j.freeradbiomed.2006.01.003","article-title":"Notoginsenoside R1 inhibits TNF-alpha-induced fibronectin production in smooth muscle cells via the ROS\/ERK pathway","volume":"40","author":"Zhang","year":"2006","journal-title":"Free Radic. Biol. Med"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.archoralbio.2011.05.010","article-title":"n-Butanol extracts of Panax notoginseng suppress LPS-induced MMP-2 expression in periodontal ligament fibroblasts and inhibit osteoclastogenesis by suppressing MAPK in LPS-activated RAW264.7 cells","volume":"56","author":"Jang","year":"2011","journal-title":"Arch. Oral Biol"},{"key":"ref_35","first-page":"181","article-title":"Carbon tetrachloride: genetic effects and other modes of action","volume":"366","author":"McGregor","year":"1996","journal-title":"Mutat. Res"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.taap.2009.11.005","article-title":"Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response","volume":"242","author":"Shim","year":"2010","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jep.2007.05.014","article-title":"The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs","volume":"112","author":"Gum","year":"2007","journal-title":"J. Ethnopharmacol"},{"key":"ref_38","first-page":"636","article-title":"Effect of a herbal medicine on fatty liver in rats fed ethanol chronically","volume":"44","author":"Horie","year":"2009","journal-title":"Nihon Arukoru Yakubutsu Igakkai Zasshi"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1248\/bpb.28.1992","article-title":"Hepatoprotective effect of 20(S)-ginsenosides Rg3 and its metabolite 20(S)-ginsenoside Rh2 on tert-butyl hydroperoxide-induced liver injury","volume":"28","author":"Lee","year":"2005","journal-title":"Biol. Pharm. Bull"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0748-5514(85)90026-1","article-title":"Pathological mechanisms in carbon tetrachloride hepatotoxicity","volume":"1","author":"Brattin","year":"1985","journal-title":"J. Free Radic. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0196-0644(86)80132-9","article-title":"Free radicals and environmental toxins","volume":"15","author":"Thomas","year":"1986","journal-title":"Ann. Emerg. Med"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00204-007-0224-3","article-title":"Protective effects of ginsenoside Rg(3) against cyclophosphamide-induced DNA damage and cell apoptosis in mice","volume":"82","author":"Zhang","year":"2008","journal-title":"Arch. Toxicol"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00204-007-0181-x","article-title":"Activation of mitogen activated protein kinase (MAPK) during carbon tetrachloride intoxication in the rat liver","volume":"81","author":"Iida","year":"2007","journal-title":"Arch. Toxicol"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.lfs.2004.02.030","article-title":"Molecular process in acute liver injury and regeneration induced by carbon tetrachloride","volume":"75","author":"Taniguchi","year":"2004","journal-title":"Life Sci"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1006\/taap.2002.9538","article-title":"Cytotoxic effect of peroxisome proliferator fenofibrate on human HepG2 hepatoma cell line and relevant mechanisms","volume":"185","author":"Jiao","year":"2002","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/0024-3205(91)90466-O","article-title":"(\u2212) deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats","volume":"48","author":"Carrillo","year":"1991","journal-title":"Life Sci."},{"key":"ref_47","first-page":"108","article-title":"Erythrocyte superoxide dismutase, glutathione peroxidase and catalase activities in healthy male subjects in Republic of Macedonia","volume":"104","author":"Bogdanska","year":"2003","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0024-3205(97)00004-0","article-title":"Free radical scavenging activities of mushroom polysaccharide extracts","volume":"60","author":"Liu","year":"1997","journal-title":"Life Sci"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/2\/2314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:49:00Z","timestamp":1760219340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/2\/2314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,21]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2012,2]]}},"alternative-id":["ijms13022314"],"URL":"https:\/\/doi.org\/10.3390\/ijms13022314","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,21]]}}}