{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:30:06Z","timestamp":1791423006802,"version":"4.3.3"},"reference-count":219,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006013","name":"UNITED ARAB EMIRATES UNIVERSITY","doi-asserted-by":"publisher","award":["31M195"],"award-info":[{"award-number":["31M195"]}],"id":[{"id":"10.13039\/501100006013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acetaminophen (APAP), which is also known as paracetamol or N-acetyl-p-aminophenol is a safe and potent drug for fever, pain and inflammation when used at its normal therapeutic doses. It is available as over-the-counter drug and used by all the age groups. The overdose results in acute liver failure that often requires liver transplantation. Current clinical therapy for APAP-induced liver toxicity is the administration of N-acetyl-cysteine (NAC), a sulphydryl compound an approved drug which acts by replenishing cellular glutathione (GSH) stores in the liver. Over the past five decades, several studies indicate that the safety and efficacy of herbal extracts or plant derived compounds that are used either as monotherapy or as an adjunct therapy along with conventional medicines for hepatotoxicity have shown favorable responses. Phytochemicals mitigate necrotic cell death and protect against APAP-induced liver toxicityby restoring cellular antioxidant defense system, limiting oxidative stress and subsequently protecting mitochondrial dysfunction and inflammation. Recent experimental evidences indicat that these phytochemicals also regulate differential gene expression to modulate various cellular pathways that are implicated in cellular protection. Therefore, in this review, we highlight the role of the phytochemicals, which are shown to be efficacious in clinically relevant APAP-induced hepatotoxicity experimental models. In this review, we have made comprehensive attempt to delineate the molecular mechanism and the cellular targets that are modulated by the phytochemicals to mediate the cytoprotective effect against APAP-induced hepatotoxicity. In this review, we have also defined the challenges and scope of phytochemicals to be developed as drugs to target APAP-induced hepatotoxicity.<\/jats:p>","DOI":"10.3390\/ijms19123776","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T11:43:44Z","timestamp":1543405424000},"page":"3776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Therapeutic Potential of Plants and Plant Derived Phytochemicals against Acetaminophen-Induced Liver Injury"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-500X","authenticated-orcid":false,"given":"Sandeep B.","family":"Subramanya","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences, PO Box # 17666, United Arab Emirates University, Al Ain 17666, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences, PO Box # 17666, United Arab Emirates University, Al Ain 17666, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6863-7372","authenticated-orcid":false,"given":"Mohamed Fizur Nagoor","family":"Meeran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, PO Box # 17666, United Arab Emirates University, Al Ain 17666, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer N.","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, SVKM\u2019s Institute of Pharmacy, Dhule, Maharashtra 424 001, India"},{"name":"Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425 405, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandragouda R.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425 405, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-2966","authenticated-orcid":false,"given":"Shreesh","family":"Ojha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, PO Box # 17666, United Arab Emirates University, Al Ain 17666, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0163-7258(93)90023-7","article-title":"Paracetamol (acetaminophen) poisoning","volume":"60","author":"Thomas","year":"1993","journal-title":"Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1055\/s-2008-1040482","article-title":"Molecular mechanisms of the hepatotoxicity caused by acetaminophen","volume":"10","author":"Nelson","year":"1990","journal-title":"Semin. Liver Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/20014091111677","article-title":"Paracetamol (acetaminophen)-induced toxicity: Molecular and biochemical mechanisms, analogues and protective approaches","volume":"31","author":"Bessems","year":"2001","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3109\/03602539709037573","article-title":"Selective protein arylation and acetaminophen-induced hepatotoxicity","volume":"29","author":"Cohen","year":"1997","journal-title":"Drug Metab. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3109\/03602532.2011.602688","article-title":"Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity","volume":"44","author":"Jaeschke","year":"2012","journal-title":"Drug Metab. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1007\/s11095-013-1007-6","article-title":"Metabolism and disposition of acetaminophen: Recent advances in relation to hepatotoxicity and diagnosis","volume":"30","author":"McGill","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.tips.2013.01.009","article-title":"Regulation of drug-induced liver injury by signal transduction pathways: Critical role of mitochondria","volume":"34","author":"Han","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13565","DOI":"10.1074\/jbc.M708916200","article-title":"Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury","volume":"283","author":"Hanawa","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.taap.2010.04.015","article-title":"c-Jun N-terminal kinase modulates oxidant stress and peroxynitrite formation independent of inducible nitric oxide synthase in acetaminophen hepatotoxicity","volume":"246","author":"Saito","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/hep.20437","article-title":"Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes","volume":"40","author":"Kon","year":"2004","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1124\/jpet.105.088898","article-title":"Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity","volume":"315","author":"Cover","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/toxsci\/kfl077","article-title":"Nuclear translocation of endonuclease G and apoptosis-inducing factor during acetaminophen-induced liver cell injury","volume":"94","author":"Bajt","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/toxsci\/67.2.322","article-title":"Mode of cell death after acetaminophen overdose in mice: Apoptosis or oncotic necrosis?","volume":"67","author":"Gujral","year":"2002","journal-title":"Toxicol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.mrfmmm.2004.04.021","article-title":"Role of cytochromes P450 in chemical toxicity and oxidative stress: Studies with CYP2E1","volume":"569","author":"Gonzalez","year":"2005","journal-title":"Mutat. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0022-3565(25)29664-1","article-title":"Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo","volume":"187","author":"Jollow","year":"1973","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/0003-9861(89)90278-6","article-title":"Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2","volume":"271","author":"Raucy","year":"1989","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/00498250802512830","article-title":"Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes","volume":"39","author":"Laine","year":"2009","journal-title":"Xenobiotica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/(SICI)1522-7146(1996)11:1<11::AID-JBT2>3.0.CO;2-Y","article-title":"Protective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in mice","volume":"11","author":"Lin","year":"1996","journal-title":"J. Biochem. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.tox.2010.01.003","article-title":"Taurine protects acetaminophen-induced oxidative damage in mice kidney through APAP urinary excretion and CYP2E1 inactivation","volume":"269","author":"Das","year":"2010","journal-title":"Toxicology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/hep.20703","article-title":"AASLD position paper: The management of acute liver failure","volume":"41","author":"Polson","year":"2005","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1056\/NEJM198812153192401","article-title":"Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)","volume":"319","author":"Smilkstein","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4292\/wjgpt.v6.i3.59","article-title":"Antioxidants in liver health","volume":"6","author":"Muriel","year":"2015","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14787","DOI":"10.3748\/wjg.v20.i40.14787","article-title":"Review of natural products with hepatoprotective effects","volume":"20","author":"Bautista","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1136\/bmj.2.5512.506","article-title":"Liver damage and impaired glucose tolerance after paracetamol overdosage","volume":"2","author":"Thomson","year":"1966","journal-title":"Br. Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0022-3565(25)29663-X","article-title":"Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism","volume":"187","author":"Mitchell","year":"1973","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.redox.2016.10.001","article-title":"Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential","volume":"10","author":"Du","year":"2016","journal-title":"Redox Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.phymed.2009.07.011","article-title":"Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice","volume":"17","author":"Wu","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1248\/bpb.31.738","article-title":"A diterpenoid acanthoic acid from Acanthopanax koreanum protects against D-galactosamine\/lipopolysaccharide-induced fulminant hepatic failure in mice","volume":"31","author":"Nan","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.ejmech.2012.01.058","article-title":"Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells","volume":"50","author":"Kaschula","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1271\/bbb.65.2555","article-title":"Protective effect of ajoene on acetaminophen-induced hepatic injury in mice","volume":"65","author":"Hattori","year":"2001","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/toxsci\/22.1.34","article-title":"The effects of 10 triterpenoid compounds on experimental liver injury in mice","volume":"22","author":"Liu","year":"1994","journal-title":"Toxicol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jep.2005.01.036","article-title":"Protective effect of alpha- and beta-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice","volume":"98","author":"Oliveira","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","first-page":"284","article-title":"Hepatoprotective activity of andrographolide against galactosamine & paracetamol intoxication in rats","volume":"92","author":"Handa","year":"1990","journal-title":"Indian J. Med. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0378-8741(93)90058-D","article-title":"Andrographolide protects rat hepatocytes against paracetamol-induced damage","volume":"40","author":"Visen","year":"1993","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1007\/s11095-012-0964-5","article-title":"Engineered andrographolide nanoparticles mitigate paracetamol hepatotoxicity in mice","volume":"30","author":"Roy","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/ptr.1084","article-title":"The effect of a water extract and anthocyanins of hibiscus sabdariffa L on paracetamol-induced hepatoxicity in rats","volume":"17","author":"Ali","year":"2003","journal-title":"Phytother. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1089\/jmf.2007.0691","article-title":"Hepatoprotective effects of an anthocyanin fraction from purple-fleshed sweet potato against acetaminophen-induced liver damage in mice","volume":"12","author":"Choi","year":"2009","journal-title":"J. Med. Food"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s12013-014-9829-3","article-title":"Oral hepatoprotective ability evaluation of purple sweet potato anthocyanins on acute and chronic chemical liver injuries","volume":"69","author":"Wang","year":"2014","journal-title":"Cell. Biochem. Biophys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1039\/c3fo60071h","article-title":"Protective effect of apigenin on mouse acute liver injury induced by acetaminophen is associated with increment of hepatic glutathione reductase activity","volume":"4","author":"Yang","year":"2013","journal-title":"Food Funct."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cbi.2007.08.001","article-title":"Arjunolic acid, a triterpenoid saponin, ameliorates arsenic-induced cyto-toxicity in hepatocytes","volume":"170","author":"Manna","year":"2007","journal-title":"Chem. Biol. Interact."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.freeradbiomed.2009.11.023","article-title":"Arjunolic acid, a triterpenoid saponin, prevents acetaminophen (APAP)-induced liver and hepatocyte injury via the inhibition of APAP bioactivation and JNK-mediated mitochondrial protection","volume":"48","author":"Ghosh","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0367-326X(99)00098-2","article-title":"Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents","volume":"71","author":"Janbaz","year":"2000","journal-title":"Fitoterapia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1042\/CS20160400","article-title":"NLRP3 inflammasome as a target of berberine in experimental murine liver injury: Interference with P2X7 signalling","volume":"130","author":"Vivoli","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.ijpharm.2014.07.027","article-title":"Bixin loaded solid lipid nanoparticles for enhanced hepatoprotection\u2014Preparation, characterisation and in vivo evaluation","volume":"473","author":"Rao","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7603\/s40681-016-0009-1","article-title":"Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury","volume":"6","author":"Chen","year":"2016","journal-title":"Biomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.freeradbiomed.2014.11.003","article-title":"Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity-implications for therapeutic targeting of Nrf2","volume":"78","author":"Olayanju","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.phymed.2003.05.002","article-title":"Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents","volume":"11","author":"Janbaz","year":"2004","journal-title":"Phytomedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.freeradbiomed.2015.12.024","article-title":"Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system","volume":"91","author":"Pang","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.cbi.2016.10.009","article-title":"Caffeic acid attenuated acetaminophen-induced hepatotoxicity by inhibiting ERK1\/2-mediated early growth response-1 transcriptional activation","volume":"260","author":"Pang","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1021\/np300095c","article-title":"Bioactive sesquiterpenoids from the rhizomes of Acorus calamus","volume":"75","author":"Hao","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4196\/kjpp.2016.20.1.15","article-title":"Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice","volume":"20","author":"Guo","year":"2016","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1124\/dmd.112.044909","article-title":"In vitro hepatotoxicity and cytochrome P450 induction and inhibition characteristics of carnosic acid, a dietary supplement with antiadipogenic properties","volume":"40","author":"Dickmann","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.cbi.2015.05.023","article-title":"The therapeutic detoxification of chlorogenic acid against acetaminophen-induced liver injury by ameliorating hepatic inflammation","volume":"238","author":"Zheng","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1631\/jzus.B1400346","article-title":"Chlorogenic acid prevents acetaminophen-induced liver injury: The involvement of CYP450 metabolic enzymes and some antioxidant signals","volume":"16","author":"Pang","year":"2015","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S0090-9556(25)07302-7","article-title":"Flavonoids, potent inhibitors of the human P-form phenolsulfotransferase. Potential role in drug metabolism and chemoprevention","volume":"24","author":"Eaton","year":"1996","journal-title":"Drug Metab. Dispos."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1248\/bpb.27.714","article-title":"Inhibitory effect of flavonoids on sulfo- and glucurono-conjugation of acetaminophen in rat cultured hepatocytes and liver subcellular preparations","volume":"27","author":"Morimitsu","year":"2004","journal-title":"Biol. Pharm. Bull."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.3109\/03639045.2015.1008012","article-title":"Systemic exposure of Paracetamol (acetaminophen) was enhanced by quercetin and chrysin co-administration in Wistar rats and in vitro model: Risk of liver toxicity","volume":"41","author":"Pingili","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_58","first-page":"331","article-title":"Protective action of corynoline, acetylcorynoline and protopine against experimental liver injury in mice","volume":"32","author":"Wei","year":"1997","journal-title":"Yao Xue Xue Bao"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1006\/phrs.1998.0353","article-title":"An assessment of the potential of protopine to inhibit microsomal drug metabolising enzymes and prevent chemical-induced hepatotoxicity in rodents","volume":"38","author":"Janbaz","year":"1998","journal-title":"Pharmacol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/0006-2952(90)90603-I","article-title":"Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes","volume":"39","author":"Donatus","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ejphar.2009.11.027","article-title":"Curcumin protects rats against acetaminophen-induced hepatorenal damages and shows synergistic activity with N.-acetyl cysteine","volume":"628","author":"Kheradpezhouh","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1016\/j.fct.2010.08.034","article-title":"Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat","volume":"48","author":"Yousef","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"58","DOI":"10.2174\/156720212799297083","article-title":"Curcumin exposure modulates multiple pro-apoptotic and anti-apoptotic signaling pathways to antagonize acetaminophen-induced toxicity","volume":"9","author":"Bulku","year":"2012","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.3748\/wjg.v19.i12.1962","article-title":"Curcumin attenuated paracetamol overdose induced hepatitis","volume":"19","author":"Somanawat","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7440","DOI":"10.3748\/wjg.v19.i42.7440","article-title":"Curcumin protects against acetaminophen-induced apoptosis in hepatic injury","volume":"19","author":"Li","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Soliman, M.M., Abdo Nassan, M., and Ismail, T.A. (2014). Immunohistochemical and molecular study on the protective effect of curcumin against hepatic toxicity induced by paracetamol in Wistar rats. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-457"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/S0278-6915(96)00057-9","article-title":"Protective effects of diallyl sulfide on acetaminophen-induced toxicities","volume":"34","author":"Hu","year":"1996","journal-title":"Food Chem. Toxicol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1006\/taap.1996.0018","article-title":"Protective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in mice","volume":"136","author":"Wang","year":"1996","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1041S","DOI":"10.1093\/jn\/131.3.1041S","article-title":"Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic","volume":"131","author":"Yang","year":"2001","journal-title":"J. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.toxlet.2012.08.005","article-title":"Dioscin, a natural steroid saponin, shows remarkable protective effect against acetaminophen-induced liver damage in vitro and in vivo","volume":"214","author":"Zhao","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.patbio.2004.01.001","article-title":"The flavonoids effect against vinblastine, cyclophosphamide and paracetamol toxicity by inhibition of lipid-peroxydation and increasing liver glutathione concentration","volume":"52","author":"Lahouel","year":"2004","journal-title":"Pathol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15","DOI":"10.7603\/s40681-015-0015-8","article-title":"Protective effects of (-)-epigallocatechin-3-gallate against acetaminophen-induced liver injury in rats","volume":"5","author":"Yao","year":"2015","journal-title":"Biomedicine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1006\/phrs.1997.0262","article-title":"Esculetin prevents liver damage induced by paracetamol and CCL4","volume":"37","author":"Gilani","year":"1998","journal-title":"Pharmacol. Res."},{"key":"ref_74","first-page":"81","article-title":"Sodium ferulate alleviated paracetamol-induced liver toxicity in mice","volume":"15","author":"Wang","year":"1994","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"ref_75","first-page":"4205","article-title":"Ferulic acid attenuated acetaminophen-induced hepatotoxicity though down-regulating the cytochrome P 2E1 and inhibiting toll-like receptor 4 signaling-mediated inflammation in mice","volume":"8","author":"Yuan","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_76","first-page":"209","article-title":"Protective effects of fulvotomentosides on acetaminophen-induced hepatotoxicity","volume":"13","author":"Liu","year":"1992","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0378-8741(94)90084-1","article-title":"The effect of Chinese hepatoprotective medicines on experimental liver injury in mice","volume":"42","author":"Liu","year":"1994","journal-title":"J. Ethnopharmacol."},{"key":"ref_78","first-page":"311","article-title":"Protective effect of the fulvotomentosides on paracetamol-induced hepatotoxicity in mice","volume":"30","author":"Shi","year":"1995","journal-title":"Yao Xue Xue Bao"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1089\/jmf.2014.3328","article-title":"Galangin Prevents Acute Hepatorenal Toxicity in Novel Propacetamol-Induced Acetaminophen-Overdosed Mice","volume":"18","author":"Tsai","year":"2015","journal-title":"J. Med. Food"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1211\/jpp.62.05.0012","article-title":"Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice","volume":"62","author":"Rasool","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.fct.2013.01.003","article-title":"Genistein protection against acetaminophen-induced liver injury via its potential impact on the activation of UDP-glucuronosyltransferase and antioxidant enzymes","volume":"55","author":"Fan","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1124\/dmd.31.7.924","article-title":"Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones","volume":"31","author":"Hu","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1211\/002235703765344540","article-title":"The effects of phytoestrogenic isoflavones on the formation and disposition of paracetamol sulfate in the isolated perfused rat liver","volume":"55","author":"Lucas","year":"2003","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1039\/C6FO00889E","article-title":"Genistein promotes the metabolic transformation of acetaminophen to glucuronic acid in human L-O2, HepG2 and Hep3b cells via the Nrf2\/Keap1 pathway","volume":"7","author":"Fan","year":"2016","journal-title":"Food Funct."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.tox.2005.11.018","article-title":"Geranylgeranylacetone protects against acetaminophen-induced hepatotoxicity by inducing heat shock protein 70","volume":"219","author":"Nishida","year":"2006","journal-title":"Toxicology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.3736\/jcim20111116","article-title":"6-gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice","volume":"9","author":"Sabina","year":"2011","journal-title":"Zhong Xi Yi Jie He Xue Bao"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.taap.2006.09.005","article-title":"Ginkgolide A contributes to the potentiation of acetaminophen toxicity by Ginkgo biloba extract in primary cultures of rat hepatocytes","volume":"217","author":"Rajaraman","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1055\/s-2006-957625","article-title":"Effect of Glycyrrhiza glabra roots and glycyrrhizin on the glucuronidation in rats","volume":"63","author":"Moon","year":"1997","journal-title":"Planta Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0378-8741(97)00026-3","article-title":"Hepatoprotective effect of the fractions of Ban-zhi-lian on experimental liver injuries in rats","volume":"56","author":"Lin","year":"1997","journal-title":"J. Ethnopharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.4314\/ahs.v15i3.42","article-title":"The protection of glycyrrhetinic acid (GA) towards acetaminophen (APAP)-induced toxicity partially through fatty acids metabolic pathway","volume":"15","author":"Yang","year":"2015","journal-title":"Afr. Health Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cbi.2009.04.013","article-title":"Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine","volume":"181","author":"Wan","year":"2009","journal-title":"Chem. Biol. Interact."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/0006-2952(93)90674-L","article-title":"Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats","volume":"46","author":"Yamada","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"ref_93","first-page":"141","article-title":"Rapid induction of hepatocyte growth factor mRNA after administration of gomisin A, a lignan component of shizandra fruits","volume":"94","author":"Shiota","year":"1996","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1021\/acs.orglett.5b03117","article-title":"Guajavadimer A, a Dimeric Caryophyllene-Derived Meroterpenoid with a New Carbon Skeleton from the Leaves of Psidium guajava","volume":"18","author":"Li","year":"2016","journal-title":"Org. Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.toxlet.2011.10.023","article-title":"Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation","volume":"208","author":"Ahmad","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1515\/jbcpp-2014-0095","article-title":"Effect of homopterocarpin, an isoflavonoid from Pterocarpus erinaceus, on indices of liver injury and oxidative stress in acetaminophen-provoked hepatotoxicity","volume":"26","author":"Akinmoladun","year":"2015","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cbi.2016.01.004","article-title":"Protective effect of hyperoside against acetaminophen (APAP) induced liver injury through enhancement of APAP clearance","volume":"246","author":"Xie","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.lfs.2016.04.002","article-title":"Hepatoprotective effect of isoquercitrin against acetaminophen-induced liver injury","volume":"152","author":"Xie","year":"2016","journal-title":"Life Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"931","DOI":"10.3109\/00498254.2016.1140847","article-title":"3,4-Dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin, attenuates acetaminophen (APAP)-induced liver injury through activation of Nrf-2","volume":"46","author":"Xue","year":"2016","journal-title":"Xenobiotica"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.jep.2005.08.038","article-title":"Effect of Cistus laurifolius L. leaf extracts and flavonoids on acetaminophen-induced hepatotoxicity in mice","volume":"103","author":"Kupeli","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_101","first-page":"19","article-title":"A new flavonoid C-glycoside from Solanum elaeagnifolium with hepatoprotective and curative activities against paracetamol-induced liver injury in mice","volume":"68","author":"Hawas","year":"2013","journal-title":"Z. Naturforsch. C"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/jbt.21814","article-title":"Lophirones B and C Attenuate Acetaminophen-Induced Liver Damage in Mice: Studies on Hepatic, Oxidative Stress and Inflammatory Biomarkers","volume":"30","author":"Ajiboye","year":"2016","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/j.fct.2012.02.042","article-title":"Lupeol protects against acetaminophen-induced oxidative stress and cell death in rat primary hepatocytes","volume":"50","author":"Kumari","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.intimp.2015.05.009","article-title":"Protective effects of luteolin against acetaminophen-induced acute liver failure in mouse","volume":"27","author":"Tai","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1515\/znc-2012-7-805","article-title":"Digalacturonide flavones from Egyptian Lantana camara flowers with in vitro antioxidant and in vivo hepatoprotective activities","volume":"67","author":"Mohammed","year":"2012","journal-title":"Z. Naturforsch. C"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1142\/S0192415X14500876","article-title":"Hepatoprotective and anti-oxidant activities of Glossogyne tenuifolia against acetaminophen-induced hepatotoxicity in mice","volume":"42","author":"Tien","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s12272-009-1139-8","article-title":"Antioxidative and hepatoprotective effects of magnolol on acetaminophen-induced liver damage in rats","volume":"32","author":"Chen","year":"2009","journal-title":"Arch. Pharm. Res."},{"key":"ref_108","first-page":"44","article-title":"Hepato-protective potential of carotenoid meso-zeaxanthin against paracetamol, CCl4 and ethanol induced toxicity","volume":"49","author":"Firdous","year":"2011","journal-title":"Indian J. Exp. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.3748\/wjg.v18.i18.2197","article-title":"Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice","volume":"18","author":"Liu","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_110","first-page":"896","article-title":"Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats","volume":"16","author":"Bohlooli","year":"2013","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1007\/s10495-015-1160-y","article-title":"Morin mitigates acetaminophen-induced liver injury by potentiating Nrf2 regulated survival mechanism through molecular intervention in PHLPP2-Akt-Gsk3beta axis","volume":"20","author":"Rizvi","year":"2015","journal-title":"Apoptosis"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1006\/taap.1993.1240","article-title":"Acetaminophen hepatotoxicity: Influence of phenobarbital and beta-naphthoflavone treatment in obese and lean Zucker rats","volume":"123","author":"Tuntaterdtum","year":"1993","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1039\/C2FO30213F","article-title":"Protective effect of naringenin against acetaminophen-induced acute liver injury in metallothionein (MT)-null mice","volume":"4","author":"Lv","year":"2013","journal-title":"Food Funct."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0300-483X(99)00136-5","article-title":"Effects of phenolic antioxidants and flavonoids on DNA synthesis in rat liver, spleen, and testis in vitro","volume":"139","author":"Wong","year":"1999","journal-title":"Toxicology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S0090-9556(25)07515-4","article-title":"Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes","volume":"22","author":"Li","year":"1994","journal-title":"Drug Metab. Dispos."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/S0022-3565(25)39456-5","article-title":"Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice","volume":"266","author":"Liu","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/S0022-3565(25)12127-7","article-title":"Effect of oleanolic acid on hepatic toxicant-activating and detoxifying systems in mice","volume":"275","author":"Liu","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tox.2007.02.014","article-title":"Role of nitric oxide and reduced glutathione in the protective effects of aminoguanidine, gadolinium chloride and oleanolic acid against acetaminophen-induced hepatic and renal damage","volume":"234","author":"Hafez","year":"2007","journal-title":"Toxicology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.bcp.2008.07.021","article-title":"New insights into generalized hepatoprotective effects of oleanolic acid: Key roles of metallothionein and Nrf2 induction","volume":"76","author":"Liu","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.bcp.2008.12.028","article-title":"Oleanolic acid activates Nrf2 and protects from acetaminophen hepatotoxicity via Nrf2-dependent and Nrf2-independent processes","volume":"77","author":"Reisman","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1016\/S0960-894X(98)00479-X","article-title":"Design and synthesis of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, a novel and highly active inhibitor of nitric oxide production in mouse macrophages","volume":"8","author":"Honda","year":"1998","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Ding, Y., Li, Q., Xu, Y., Chen, Y., Deng, Y., Zhi, F., and Qian, K. (2016). Attenuating Oxidative Stress by Paeonol Protected against Acetaminophen-Induced Hepatotoxicity in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154375"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1248\/bpb.27.1555","article-title":"The inhibitory effect of intestinal bacterial metabolite of ginsenosides on CYP3A activity","volume":"27","author":"Liu","year":"2004","journal-title":"Biol. Pharm. Bull."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1111\/liv.12329","article-title":"Panaxatriol saponin ameliorated liver injury by acetaminophen via restoring thioredoxin-1 and pro-caspase-12","volume":"34","author":"Wang","year":"2014","journal-title":"Liver Int."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"957947","DOI":"10.1155\/2013\/957947","article-title":"The amelioration of N-acetyl-p-benzoquinone imine toxicity by ginsenoside Rg3: The role of Nrf2-mediated detoxification and Mrp1\/Mrp3 transports","volume":"2013","author":"Gum","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8668","DOI":"10.1021\/jf5027247","article-title":"Antioxidant defense and hepatoprotection by procyanidins from almond (Prunus amygdalus) skins","volume":"62","author":"Truong","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/jbt.21604","article-title":"Protective effects of pterostilbene against acetaminophen-induced hepatotoxicity in rats","volume":"29","author":"Mansour","year":"2015","journal-title":"J. Biochem. Mol. Toxicol"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/ptr.816","article-title":"Antioxidant and hepatoprotective effects of punicalagin and punicalin on acetaminophen-induced liver damage in rats","volume":"15","author":"Lin","year":"2001","journal-title":"Phytother. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"S619","DOI":"10.1042\/bst025s619","article-title":"Quercetin exhibits hepatoprotective activity in rats","volume":"25","author":"Gilani","year":"1997","journal-title":"Biochem. Soc. Trans."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3109\/03602532.2012.713969","article-title":"Inhibition and induction of glutathione S-transferases by flavonoids: Possible pharmacological and toxicological consequences","volume":"44","author":"Bousova","year":"2012","journal-title":"Drug Metab. Rev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.pathophys.2014.12.002","article-title":"Quercetin protects against acetaminophen-induced hepatorenal toxicity by reducing reactive oxygen and nitrogen species","volume":"22","author":"Mohamadin","year":"2015","journal-title":"Pathophysiology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/jps.23834","article-title":"Design and optimization of self-nanoemulsifying delivery system to enhance quercetin hepatoprotective activity in paracetamol-induced hepatotoxicity","volume":"103","author":"Ahmed","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.freeradbiomed.2015.03.035","article-title":"The involvement of p62-Keap1-Nrf2 antioxidative signaling pathway and JNK in the protection of natural flavonoid quercetin against hepatotoxicity","volume":"85","author":"Ji","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"S477","DOI":"10.33549\/physiolres.933205","article-title":"Sirtuin 1 modulation in rat model of acetaminophen-induced hepatotoxicity","volume":"64","author":"Wojnarova","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.toxlet.2015.05.001","article-title":"Hepato-protective effect of resveratrol against acetaminophen-induced liver injury is associated with inhibition of CYP-mediated bioactivation and regulation of SIRT1-p53 signaling pathways","volume":"236","author":"Wang","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.fct.2015.04.014","article-title":"Resveratrol prevents protein nitration and release of endonucleases from mitochondria during acetaminophen hepatotoxicity","volume":"81","author":"Du","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cbi.2008.10.028","article-title":"Th1\/Th2 cytokine balance as a determinant of acetaminophen-induced liver injury","volume":"179","author":"Masubuchi","year":"2009","journal-title":"Chem. Biol. Interact."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.hepres.2006.02.005","article-title":"Protective effects of resveratrol against acetaminophen-induced toxicity in mice","volume":"35","author":"Sener","year":"2006","journal-title":"Hepatol. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.fct.2015.11.003","article-title":"Critical review of resveratrol in xenobiotic-induced hepatotoxicity","volume":"86","author":"McGill","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/j.1478-3231.2010.02295.x","article-title":"Resveratrol and liver disease: From bench to bedside and community","volume":"30","author":"Bishayee","year":"2010","journal-title":"Liver Int."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1016\/j.fct.2011.04.011","article-title":"Rhein protects against acetaminophen-induced hepatic and renal toxicity","volume":"49","author":"Zhao","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0367-326X(02)00217-4","article-title":"Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents","volume":"73","author":"Janbaz","year":"2002","journal-title":"Fitoterapia"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cbi.2014.09.012","article-title":"Saikosaponin d protects against acetaminophen-induced hepatotoxicity by inhibiting NF-kappaB and STAT3 signaling","volume":"223","author":"Liu","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1248\/bpb.31.1523","article-title":"Protective effects of salidroside against acetaminophen-induced toxicity in mice","volume":"31","author":"Wu","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3109\/13880209.2013.863946","article-title":"An LC-MS\/MS method for the determination of salidroside and its metabolite p-tyrosol in rat liver tissues","volume":"52","author":"Guo","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/jphp.12381","article-title":"Danshen (Salvia miltiorrhiza) water extract inhibits paracetamol-induced toxicity in primary rat hepatocytes via reducing CYP2E1 activity and oxidative stress","volume":"67","author":"Zhou","year":"2015","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jphs.2014.12.010","article-title":"Salvianolic acid B protects against acetaminophen hepatotoxicity by inducing Nrf2 and phase II detoxification gene expression via activation of the PI3K and PKC signaling pathways","volume":"127","author":"Lin","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"757126","DOI":"10.1155\/2013\/757126","article-title":"Hepatoprotective and antioxidant effects of saponarin, isolated from Gypsophila trichotoma Wend. on paracetamol-induced liver damage in rats","volume":"2013","author":"Simeonova","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1248\/bpb.26.1428","article-title":"Sauchinone, a lignan from Saururus chinensis, inhibits staurosporine-induced apoptosis in C6 rat glioma cells","volume":"26","author":"Song","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1111\/j.1476-5381.2010.01095.x","article-title":"Nrf2-mediated liver protection by sauchinone, an antioxidant lignan, from acetaminophen toxicity through the PKCdelta-GSK3beta pathway","volume":"163","author":"Kay","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cbi.2015.02.022","article-title":"Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation","volume":"231","author":"Jiang","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/toxsci\/kfu216","article-title":"Schisandrol B protects against acetaminophen-induced hepatotoxicity by inhibition of CYP-mediated bioactivation and regulation of liver regeneration","volume":"143","author":"Jiang","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/aps.2015.120","article-title":"Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2\/ARE signaling pathway","volume":"37","author":"Jiang","year":"2016","journal-title":"Acta pharmacol. Sin."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/SHK.0b013e31818ede6f","article-title":"The protective effect of sesamol against mitochondrial oxidative stress and hepatic injury in acetaminophen-overdosed rats","volume":"32","author":"Chandrasekaran","year":"2009","journal-title":"Shock"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1177\/0960327110394226","article-title":"Anti-hepatotoxic effects of 3,4-methylenedioxyphenol and N-acetylcysteine in acutely acetaminophen-overdosed mice","volume":"30","author":"Chandrasekaran","year":"2011","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_156","first-page":"375","article-title":"Acetaminophen hepatotoxicity in rats is attenuated by silybin dihemisuccinate","volume":"280","author":"Campos","year":"1988","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1055\/s-2006-962055","article-title":"Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver","volume":"55","author":"Campos","year":"1989","journal-title":"Planta Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-0773.1991.tb00400.x","article-title":"Acetaminophen does not induce oxidative stress in isolated rat hepatocytes: Its probable antioxidant effect is potentiated by the flavonoid silybin","volume":"69","author":"Garrido","year":"1991","journal-title":"Pharmacol. Toxicol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1254\/jjp.60.315","article-title":"Protective activity of silipide on liver damage in rodents","volume":"60","author":"Conti","year":"1992","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1248\/cpb.57.79","article-title":"Determination of sweroside in rat plasma and bile for oral bioavailability and hepatobiliary excretion","volume":"57","author":"Luo","year":"2009","journal-title":"Chem. Pharm. Bull."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/jms.3429","article-title":"Characterization of metabolites of sweroside in rat urine using ultra-high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry and NMR spectroscopy","volume":"49","author":"Han","year":"2014","journal-title":"J. Mass Spectrom."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1515\/JBCPP.2010.21.4.369","article-title":"Protective effects of syringic acid against acetaminophen-induced hepatic damage in albino rats","volume":"21","author":"Ramachandran","year":"2010","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.intimp.2017.03.027","article-title":"Multi-targeted protection of acetaminophen-induced hepatotoxicity in mice by tannic acid","volume":"47","author":"Zhang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.fct.2010.05.072","article-title":"Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver","volume":"48","author":"Nagi","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.bcp.2015.07.024","article-title":"Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice","volume":"97","author":"Jadeja","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.fitote.2014.11.006","article-title":"Penthorin A and B, two unusual 2,4\u2032-epoxy-8,5\u2032-neolignans from Penthorum chinese","volume":"100","author":"He","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"15440","DOI":"10.3390\/molecules191015440","article-title":"A new isoflavonoid from seeds of Lepidium sativum L. and its protective effect on hepatotoxicity induced by paracetamol in male rats","volume":"19","author":"Sakran","year":"2014","journal-title":"Molecules"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1177\/0960327115627688","article-title":"The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2)","volume":"35","author":"Palabiyik","year":"2016","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/j.1472-8206.2009.00722.x","article-title":"Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice","volume":"23","author":"Girish","year":"2009","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.intimp.2017.01.028","article-title":"Astaxanthin pretreatment attenuates acetaminophen-induced liver injury in mice","volume":"45","author":"Zhang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1142\/S0192415X17500082","article-title":"ERK Signaling Pathway Plays a Key Role in Baicalin Protection Against Acetaminophen-Induced Liver Injury","volume":"45","author":"Liao","year":"2017","journal-title":"Am. J. Chin. Med."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Liao, C.C., Day, Y.J., Lee, H.C., Liou, J.T., Chou, A.H., and Liu, F.C. (2016). Baicalin Attenuates IL-17-Mediated Acetaminophen-Induced Liver Injury in a Mouse Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166856"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1016\/j.jnutbio.2013.05.007","article-title":"Chlorogenic acid, a dietary polyphenol, protects acetaminophen-induced liver injury and its mechanism","volume":"24","author":"Ji","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.freeradbiomed.2016.11.009","article-title":"Nrf2-mediated liver protection by esculentoside A against acetaminophen toxicity through the AMPK\/Akt\/GSK3beta pathway","volume":"101","author":"Wang","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1124\/dmd.116.069419","article-title":"Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor alpha-Mediated Apoptosis","volume":"44","author":"Yan","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.biopha.2016.08.044","article-title":"Effects of luteolin and quercetin 3-beta-d-glucoside identified from Passiflora subpeltata leaves against acetaminophen induced hepatotoxicity in rats","volume":"83","author":"Shanmugam","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cbi.2016.12.011","article-title":"Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL\/6 mice","volume":"263","author":"Bandeira","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.bmc.2016.12.018","article-title":"Lycopene pretreatment improves hepatotoxicity induced by acetaminophen in C57BL\/6 mice","volume":"25","author":"Bandeira","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Truong, V.L., Ko, S.Y., Jun, M., and Jeong, W.S. (2016). Quercitrin from Toona sinensis (Juss.) M.Roem. Attenuates Acetaminophen-Induced Acute Liver Toxicity in HepG2 Cells and Mice through Induction of Antioxidant Machinery and Inhibition of Inflammation. Nutrients, 8.","DOI":"10.3390\/nu8070431"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.biopha.2016.12.014","article-title":"Acetaminophen-induced hepatotoxicity: Preventive effect of trans anethole","volume":"86","author":"Ritter","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.freeradbiomed.2016.10.003","article-title":"Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms","volume":"101","author":"Palliyaguru","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"12538","DOI":"10.1016\/j.cbi.2006.03.008","article-title":"Liquiritigenin, an aglycone of liquiritin in Glycyrrhizae radix, prevents acute liver injuries in rats induced by acetaminophen with or without buthionine sulfoximine","volume":"161","author":"Kim","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.lfs.2012.01.012","article-title":"Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax\/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade","volume":"90","author":"Kumari","year":"2012","journal-title":"Life Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"74","DOI":"10.14202\/vetworld.2017.74-80","article-title":"Protective effect of rutin in comparison to silymarin against induced hepatotoxicity in rats","volume":"10","author":"Reddy","year":"2017","journal-title":"Vet. World"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0300-483X(03)00256-7","article-title":"Antioxidants protect primary rat hepatocyte cultures against acetaminophen-induced DNA strand breaks but not against acetaminophen-induced cytotoxicity","volume":"191","author":"Lewerenz","year":"2003","journal-title":"Toxicology"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1006\/taap.1995.1175","article-title":"Suppression of liver cytochrome P450 by alpha-hederin: Relevance to hepatoprotection","volume":"134","author":"Liu","year":"1995","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Iorga, A., Dara, L., and Kaplowitz, N. (2017). Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051018"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1586\/17474124.2015.1060855","article-title":"Sterile inflammation in acute liver injury: Myth or mystery?","volume":"9","author":"Woolbright","year":"2015","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.phymed.2008.12.018","article-title":"Synergy research: Approaching a new generation of phytopharmaceuticals","volume":"16","author":"Wagner","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_190","first-page":"13","article-title":"Hepatoprotective activity of Ocimum sanctum alcoholic leaf extract against paracetamol-induced liver damage in Albino rats","volume":"3","author":"Lahon","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jep.2007.01.008","article-title":"Hepatoprotective potential of Aloe barbadensis Mill. against carbon tetrachloride induced hepatotoxicity","volume":"111","author":"Chandan","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jep.2009.10.019","article-title":"Hepatoprotective activity of ethanolic extracts of bark of Zanthoxylum armatum DC in CCl4 induced hepatic damage in rats","volume":"127","author":"Ranawat","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jep.2009.09.009","article-title":"The hepatoprotective and antifibrotic effects of Saururus chinensis against carbon tetrachloride induced hepatic fibrosis in rats","volume":"126","author":"Wang","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jep.2008.02.023","article-title":"Hepatoprotective effects of Ganoderma lucidum peptides against D-galactosamine-induced liver injury in mice","volume":"117","author":"Shi","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1021\/jf020946n","article-title":"Hepatoprotective effect of myristicin from nutmeg (Myristica fragrans) on lipopolysaccharide\/d-galactosamine-induced liver injury","volume":"51","author":"Morita","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1055\/s-2006-957596","article-title":"Preventive effect of lithospermate B from Salvia miltiorhiza on experimental hepatitis induced by carbon tetrachloride or D-galactosamine\/lipopolysaccharide","volume":"63","author":"Hase","year":"1997","journal-title":"Planta Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3390\/antiox4010204","article-title":"Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives","volume":"4","author":"Surai","year":"2015","journal-title":"Antioxidants"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4254\/wjh.v6.i3.144","article-title":"Hepatoprotective effect of silymarin","volume":"6","year":"2014","journal-title":"World J. Hepatol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"538317","DOI":"10.1155\/2015\/538317","article-title":"Hepatoprotective Effect of Silymarin (Silybum marianum) on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats","volume":"2015","author":"Freitag","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1124\/dmd.107.017004","article-title":"Hepatobiliary excretion of silibinin in normal and liver cirrhotic rats","volume":"36","author":"Wu","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.annemergmed.2006.12.015","article-title":"Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model","volume":"50","author":"Tong","year":"2007","journal-title":"Ann. Emerg. Med."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Papackova, Z., Heczkova, M., Dankova, H., Sticova, E., Lodererova, A., Bartonova, L., Poruba, M., and Cahova, M. (2018). Silymarin prevents acetaminophen-induced hepatotoxicity in mice. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191353"},{"key":"ref_203","first-page":"222","article-title":"Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent","volume":"15","author":"Lirussi","year":"2002","journal-title":"Diabetes Nutr. Metab."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/ptr.1988","article-title":"The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: A randomized, double-blind, placebo-controlled, clinical trial","volume":"20","author":"Huseini","year":"2006","journal-title":"Phytother. Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3109\/19390211.2013.859217","article-title":"Hepatoprotective action of Echinophora platyloba DC leaves against acute toxicity of acetaminophen in rats","volume":"11","author":"Heidarian","year":"2014","journal-title":"J. Diet. Suppl."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"5004","DOI":"10.3748\/wjg.v23.i27.5004","article-title":"Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis","volume":"23","author":"Pereira","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_207","first-page":"3046373","article-title":"Potential Effects of Silymarin and Its Flavonolignan Components in Patients with beta-Thalassemia Major: A Comprehensive Review in 2015","volume":"2016","author":"Salehifar","year":"2016","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"941085","DOI":"10.1155\/2014\/941085","article-title":"Effects and tolerance of silymarin (milk thistle) in chronic hepatitis C virus infection patients: A meta-analysis of randomized controlled trials","volume":"2014","author":"Yang","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.phymed.2004.10.003","article-title":"The efficacy of Liv-52 on liver cirrhotic patients: A randomized, double-blind, placebo-controlled first approach","volume":"12","author":"Huseini","year":"2005","journal-title":"Phytomedicine"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"3876040","DOI":"10.1155\/2017\/3876040","article-title":"Antioxidants of Phyllanthus emblica L. Bark Extract Provide Hepatoprotection against Ethanol-Induced Hepatic Damage: A Comparison with Silymarin","volume":"2017","author":"Chaphalkar","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1080\/14786419.2014.971795","article-title":"Evaluation of hepatoprotective activity of aqueous extracts of leaves of Basella alba in albino rats","volume":"29","author":"Das","year":"2015","journal-title":"Nat. Prod. Res."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Zakaria, Z.A., Yahya, F., Mamat, S.S., Mahmood, N.D., Mohtarrudin, N., Taher, M., Hamid, S.S., Teh, L.K., and Salleh, M.Z. (2016). Hepatoprotective action of various partitions of methanol extract of Bauhinia purpurea leaves against paracetamol-induced liver toxicity: Involvement of the antioxidant mechanisms. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1110-4"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/aps.2013.202","article-title":"Inhibitory effects of phytochemicals on metabolic capabilities of CYP2D6(*)1 and CYP2D6(*)10 using cell-based models in vitro","volume":"35","author":"Qu","year":"2014","journal-title":"Acta pharmacol. Sin."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.taap.2015.11.016","article-title":"Experimental models of hepatotoxicity related to acute liver failure","volume":"290","author":"Maes","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00204-013-1078-5","article-title":"Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME","volume":"87","author":"Godoy","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1517\/17425255.2015.1071353","article-title":"Pathophysiological significance of c-jun N-terminal kinase in acetaminophen hepatotoxicity","volume":"11","author":"Du","year":"2015","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1002\/hep.24132","article-title":"HepaRG cells: A human model to study mechanisms of acetaminophen hepatotoxicity","volume":"53","author":"McGill","year":"2011","journal-title":"Hepatology"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.taap.2014.05.010","article-title":"Mechanisms of acetaminophen-induced cell death in primary human hepatocytes","volume":"279","author":"Xie","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.lfs.2011.01.025","article-title":"Current issues with acetaminophen hepatotoxicity\u2014A clinically relevant model to test the efficacy of natural products","volume":"88","author":"Jaeschke","year":"2011","journal-title":"Life Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/12\/3776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:41:43Z","timestamp":1775284903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/12\/3776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,28]]},"references-count":219,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["ijms19123776"],"URL":"https:\/\/doi.org\/10.3390\/ijms19123776","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,28]]}}}