{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:12:32Z","timestamp":1793045552229,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFC1600305"],"award-info":[{"award-number":["2017YFC1600305"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This study investigates the protective effect of baicalein on carbon tetrachloride (CCl4)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg\/kg\/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg\/kg was i.p. injected in mice at 2 and 24 h prior to CCl4 injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl4 exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-\u03baB) pathway, activated the erythroid 2-related factor 2 (Nrf2)\/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl4-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl4. In vitro, baicalein treatment improved CCl4 -induced decreases of cell viabilities and knockdown of Nrf2 and arachidonate 12-lipoxygenase (ALOX12) genes partly abolished the protective effect of baicalein on CCl4 -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl4-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-\u03baB pathways.<\/jats:p>","DOI":"10.3390\/antiox10060976","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T11:19:20Z","timestamp":1624015160000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Inhibition of Oxidative Stress and ALOX12 and NF-\u03baB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4677-0524","authenticated-orcid":false,"given":"Chongshan","family":"Dai","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusheng","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0017-7952","authenticated-orcid":false,"given":"Tony","family":"Velkov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2019.03.004","article-title":"Global liver disease burdens and research trends: Analysis from a chinese perspective","volume":"71","author":"Xiao","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_2","first-page":"363","article-title":"Drug-induced liver toxicity and prevention by herbal antioxidants: An overview","volume":"6","author":"Singh","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1111\/j.1478-3231.2010.02262.x","article-title":"Acute liver failure: Mechanisms of immune-mediated liver injury","volume":"30","author":"Wu","year":"2010","journal-title":"Liver Int."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Niu, L., Cui, X., Qi, Y., Xie, D., Wu, Q., Chen, X., Ge, J., and Liu, Z. (2016). Involvement of tgf-beta1\/smad3 signaling in carbon tetrachloride-induced acute liver injury in mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156090"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3892\/ijmm.2017.3028","article-title":"Protective effect of human serum amyloid p on ccl4-induced acute liver injury in mice","volume":"40","author":"Cong","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.taap.2016.11.006","article-title":"Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation","volume":"314","author":"Zhang","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/toxsci\/kfu244","article-title":"Cyclooxygenase-1 serves a vital hepato-protective function in chemically induced acute liver injury","volume":"143","author":"Xiao","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1042\/BJ20111451","article-title":"Autophagy, mitochondria and oxidative stress: Cross-talk and redox signalling","volume":"441","author":"Lee","year":"2012","journal-title":"Biochem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1111\/jcmm.13048","article-title":"Emerging role of hmgb1 in lung diseases: Friend or foe","volume":"21","author":"Ding","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.biopha.2017.07.074","article-title":"Rac2 deficiency attenuates ccl4-induced liver injury through suppressing inflammation and oxidative stress","volume":"94","author":"Zou","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jep.2017.02.018","article-title":"Protective effect of a polysaccharide from anoectochilus roxburghii against carbon tetrachloride-induced acute liver injury in mice","volume":"200","author":"Zeng","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.fct.2016.09.009","article-title":"Pequi (caryocar brasiliense camb.) almond oil attenuates carbon tetrachloride-induced acute hepatic injury in rats: Antioxidant and anti-inflammatory effects","volume":"97","author":"Torres","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, M., Niu, J., Ou, L., Deng, B., Wang, Y., and Li, S. (2019). Zerumbone protects against carbon tetrachloride (ccl4)-induced acute liver injury in mice via inhibiting oxidative stress and the inflammatory response: Involving the tlr4\/nf-kappab\/cox-2 pathway. Molecules, 24.","DOI":"10.3390\/molecules24101964"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Peng, X., Dai, C., Liu, Q., Li, J., and Qiu, J. (2018). Curcumin attenuates on carbon tetrachloride-induced acute liver injury in mice via modulation of the nrf2\/ho-1 and tgf-beta1\/smad3 pathway. Molecules, 23.","DOI":"10.3390\/molecules23010215"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1038\/s41419-018-1136-2","article-title":"Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis","volume":"9","author":"Dai","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.tox.2010.11.005","article-title":"Hepatoprotective activity of berberine is mediated by inhibition of tnf-alpha, cox-2, and inos expression in ccl(4)-intoxicated mice","volume":"280","author":"Domitrovic","year":"2011","journal-title":"Toxicology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.biopha.2018.02.041","article-title":"Sesquiterpenoids from the root of panax ginseng protect ccl4-induced acute liver injury by anti-inflammatory and anti-oxidative capabilities in mice","volume":"102","author":"Wang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8390","DOI":"10.1073\/pnas.1821277116","article-title":"Mechanistic basis for impaired ferroptosis in cells expressing the african-centric s47 variant of p53","volume":"116","author":"Leu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","first-page":"8655","article-title":"N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the nrf2\/ho-1 pathway","volume":"8","author":"Cai","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/1440-1681.12591","article-title":"Deferoxamine alleviates liver fibrosis induced by ccl4 in rats","volume":"43","author":"Mohammed","year":"2016","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"850","DOI":"10.14336\/AD.2017.0829","article-title":"The effects of baicalin and baicalein on cerebral ischemia: A review","volume":"8","author":"Liang","year":"2017","journal-title":"Aging Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sahu, B.D., Kumar, J.M., and Sistla, R. (2015). Baicalein, a bioflavonoid, prevents cisplatin-induced acute kidney injury by up-regulating antioxidant defenses and down-regulating the mapks and nf-kappa b pathways. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134139"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.phrs.2015.08.021","article-title":"The effects of baicalein and baicalin on mitochondrial function and dynamics: A review","volume":"100","author":"Nabavi","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1021\/jf301511m","article-title":"Baicalein protects against 6-ohda-induced neurotoxicity through activation of keap1\/nrf2\/ho-1 and involving pkcalpha and pi3k\/akt signaling pathways","volume":"60","author":"Zhang","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","first-page":"181","article-title":"Baicalein, a component of scutellaria baicalensis, attenuates kidney injury induced by myocardial ischemia and reperfusion","volume":"82","author":"Lai","year":"2016","journal-title":"Planta Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbrc.2020.11.109","article-title":"Baicalein attenuates acute liver injury by blocking nlrp3 inflammasome","volume":"534","author":"Xiao","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1093\/jac\/dkx185","article-title":"Baicalein acts as a nephroprotectant that ameliorates colistin-induced nephrotoxicity by activating the antioxidant defence mechanism of the kidneys and down-regulating the inflammatory response","volume":"72","author":"Dai","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhou, H.C., Wang, H., Shi, K., Li, J.M., Zong, Y., and Du, R. (2018). Hepatoprotective effect of baicalein against acetaminophen-induced acute liver injury in mice. Molecules, 24.","DOI":"10.3390\/molecules24010131"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41419-020-2334-2","article-title":"Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure","volume":"11","author":"Yamada","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Popovi\u0107, D., Koci\u0107, G., Kati\u0107, V., Zarubica, A., Veli\u010dkovi\u0107, L.J., Ni\u010dkovi\u0107, V.P., Jovi\u0107, A., Veljkovi\u0107, A., Petrovi\u0107, V., and Raki\u0107, V. (2019). Anthocyanins protect hepatocytes against ccl(4)-induced acute liver injury in rats by inhibiting pro-inflammatory mediators, polyamine catabolism, lipocalin-2, and excessive proliferation of kupffer cells. Antioxidants, 8.","DOI":"10.3390\/antiox8100451"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s10620-014-3422-x","article-title":"Hepatic decompensation likely attributable to simeprevir in patients with advanced cirrhosis","volume":"60","author":"Stine","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1016\/j.bbagen.2013.02.008","article-title":"Natural products: A continuing source of novel drug leads","volume":"1830","author":"Cragg","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0002-9440(10)65594-0","article-title":"Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride","volume":"153","author":"Shi","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1089\/jmf.2007.555","article-title":"Curcumin or saikosaponin a improves hepatic antioxidant capacity and protects against ccl4-induced liver injury in rats","volume":"11","author":"Wu","year":"2008","journal-title":"J. Med. Food"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4075","DOI":"10.1128\/AAC.00070-14","article-title":"Colistin-induced nephrotoxicity in mice involves the mitochondrial, death receptor, and endoplasmic reticulum pathways","volume":"58","author":"Dai","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1080\/0886022X.2018.1532910","article-title":"Baicalein protects renal tubular epithelial cells againsthypoxia-reoxygenation injury","volume":"40","author":"Chen","year":"2018","journal-title":"Ren. Fail."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.lfs.2015.11.018","article-title":"Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice","volume":"144","author":"Sahu","year":"2016","journal-title":"Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jinorgbio.2008.11.003","article-title":"Iron-binding and anti-fenton properties of baicalein and baicalin","volume":"103","author":"Perez","year":"2009","journal-title":"J. Inorg. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.fct.2016.06.025","article-title":"Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of nrf2\/ho-1 and nf-kb pathway in human hepatocyte l02 cells","volume":"95","author":"Dai","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.cbi.2010.09.008","article-title":"Baicalein inhibits nuclear factor-kappab and apoptosis via c-flip and mapk in d-galn\/lps induced acute liver failure in murine models","volume":"188","author":"Wu","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1080\/08923970802709197","article-title":"Biochemical and cellular toxicology of peroxynitrite: Implications in cell death and autoimmune phenomenon","volume":"31","author":"Ahmad","year":"2009","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"798","DOI":"10.3892\/ijmm.2016.2460","article-title":"Baicalein protects c6 glial cells against hydrogen peroxide-induced oxidative stress and apoptosis through regulation of the nrf2 signaling pathway","volume":"37","author":"Choi","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1128\/AAC.03925-14","article-title":"Lycopene attenuates colistin-induced nephrotoxicity in mice via activation of the nrf2\/ho-1 pathway","volume":"59","author":"Dai","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/s41417-020-0170-2","article-title":"Transcription factors in ferroptotic cell death","volume":"27","author":"Dai","year":"2020","journal-title":"Cancer Gene Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1002\/jcp.24900","article-title":"Baicalein decreases hydrogen peroxide-induced damage to ng108-15 cells via upregulation of nrf2","volume":"230","author":"Yeh","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bcp.2018.01.026","article-title":"Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating nrf2 antioxidative pathway: The involvement of erk1\/2 and pkc","volume":"150","author":"Shi","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"145","DOI":"10.7150\/ijms.27005","article-title":"Activation of the nrf2\/ho-1 signaling pathway contributes to the protective effects of baicalein against oxidative stress-induced DNA damage and apoptosis in hei193 schwann cells","volume":"16","author":"Jeong","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/hep.28251","article-title":"Activation of the p62-keap1-nrf2 pathway protects against ferroptosis in hepatocellular carcinoma cells","volume":"63","author":"Sun","year":"2016","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3109\/15376516.2012.754533","article-title":"Effect of colistin exposure on calcium homeostasis and mitochondria functions in chick cortex neurons","volume":"23","author":"Dai","year":"2013","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.redox.2015.09.040","article-title":"Critical role of c-jun n-terminal protein kinase in promoting mitochondrial dysfunction and acute liver injury","volume":"6","author":"Jang","year":"2015","journal-title":"Redox Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/s10495-020-01608-2","article-title":"A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis","volume":"25","author":"Yu","year":"2020","journal-title":"Apoptosis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4149\/gpb_2019014","article-title":"Activation of the nrf2\/ho-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in hacat keratinocytes","volume":"38","author":"Choi","year":"2019","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.fct.2012.12.041","article-title":"Protection of the flavonoid fraction from rosa laevigata michx fruit against carbon tetrachloride-induced acute liver injury in mice","volume":"55","author":"Zhang","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12637","DOI":"10.18632\/oncotarget.14478","article-title":"Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting autophagy in mice","volume":"8","author":"Shi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1208\/s12248-017-0133-1","article-title":"Dibenzoylmethane protects against ccl4-induced acute liver injury by activating nrf2 via jnk, ampk, and calcium signaling","volume":"19","author":"Cao","year":"2017","journal-title":"AAPS J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12250","DOI":"10.3390\/molecules200712250","article-title":"Protective effect of procyanidin b2 against ccl4-induced acute liver injury in mice","volume":"20","author":"Yang","year":"2015","journal-title":"Molecules"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and nf-kappab signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3389\/fphar.2018.00793","article-title":"Semi-mechanism-based pharmacodynamic model for the anti-inflammatory effect of baicalein in lps-stimulated raw264.7 macrophages","volume":"9","author":"Xiang","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ejphar.2010.01.002","article-title":"Antifibrotic effects of chronic baicalein administration in a ccl4 liver fibrosis model in rats","volume":"631","author":"Sun","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6605","DOI":"10.3748\/wjg.v18.i45.6605","article-title":"Hepatoprotective effects of baicalein against ccl(4)-induced acute liver injury in mice","volume":"18","author":"Huang","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"G546","DOI":"10.1152\/ajpgi.00431.2011","article-title":"Hepatocyte-specific ablation of spermine\/spermidine-n1-acetyltransferase gene reduces the severity of ccl4-induced acute liver injury","volume":"303","author":"Zahedi","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_64","first-page":"480714","article-title":"Hispolon protects against acute liver damage in the rat by inhibiting lipid peroxidation, proinflammatory cytokine, and oxidative stress and downregulating the expressions of inos, cox-2, and mmp-9","volume":"2012","author":"Huang","year":"2012","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.bbrc.2016.03.052","article-title":"Identification of baicalein as a ferroptosis inhibitor by natural product library screening","volume":"473","author":"Xie","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by gpx4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1073\/pnas.1821022116","article-title":"Ferroptosis as a target for protection against cardiomyopathy","volume":"116","author":"Fang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"638","DOI":"10.3389\/fphar.2019.00638","article-title":"Baicalein exerts neuroprotective effects in fecl3-induced posttraumatic epileptic seizures via suppressing ferroptosis","volume":"10","author":"Li","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5355","DOI":"10.1158\/0008-5472.CAN-19-0369","article-title":"Stearoyl-coa desaturase 1 protects ovarian cancer cells from ferroptotic cell death","volume":"79","author":"Tesfay","year":"2019","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s00395-014-0414-0","article-title":"Hypoxic preconditioning protects rat hearts against ischemia-reperfusion injury via the arachidonate12-lipoxygenase\/transient receptor potential vanilloid 1 pathway","volume":"109","author":"Lu","year":"2014","journal-title":"Basic Res. Cardiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"22265","DOI":"10.1038\/s41598-020-79400-0","article-title":"Gigantol ameliorates ccl4-induced liver injury via preventing activation of jnk\/cpla2\/12-lox inflammatory pathway","volume":"10","author":"Xue","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jep.2014.08.031","article-title":"Safety, tolerability, and pharmacokinetics of a single ascending dose of baicalein chewable tablets in healthy subjects","volume":"156","author":"Li","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s40261-016-0418-7","article-title":"Multiple-ascending-dose pharmacokinetics and safety evaluation of baicalein chewable tablets in healthy chinese volunteers","volume":"36","author":"Pang","year":"2016","journal-title":"Clin. 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