{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T08:12:10Z","timestamp":1782029530450,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species\u2014including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)\u2014and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography\u2013photodiode array detector (HPLC-DAD). We further evaluated the hepatoprotective effects of these extracts on CCl4-induced acute liver damage in C57BL\/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG) contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl4. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic necrosis caused by CCl4. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA) levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu\/Zn-superoxide dismutase (Cu\/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and glutathione S-transferase (GST) proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (\u03b1 and \u03b2). Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl4-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.<\/jats:p>","DOI":"10.3390\/ijms19051329","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T03:45:49Z","timestamp":1525059949000},"page":"1329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL\/6 Mice"],"prefix":"10.3390","volume":"19","author":[{"given":"Zi-Wei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"Taichung Armed Forces General Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"The School of Chinese Medicines for Post-Baccalaureate, I-Shou University, Kaohsiung County 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan-Hsuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"The School of Chinese Medicines for Post-Baccalaureate, I-Shou University, Kaohsiung County 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Chi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Golden-Ager Industry Management, College of Management, Chaoyang University of Technology, Taichung 41394, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7036-5035","authenticated-orcid":false,"given":"Chi-Rei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.7326\/0003-4819-137-12-200212170-00007","article-title":"Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States","volume":"137","author":"Ostapowicz","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, W., Dong, Z., Chang, X., Zhang, C., Rong, G., Gao, X., Zeng, Z., Wang, C., Chen, Y., and Rong, Y. (2018). Protective effect of the total flavonoids from Apocynum venetum L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo. J. Physiol. Biochem.","DOI":"10.1007\/s13105-018-0618-0"},{"key":"ref_3","first-page":"2228","article-title":"Hepatoprotective effect of methyl ferulic acid against carbon tetrachloride-induced acute liver injury in rats","volume":"15","author":"Yang","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1177\/0960327117693066","article-title":"Molecular hepatoprotective effects of lipoic acid against carbon tetrachloride-induced liver fibrosis in rats: Hepatoprotection at molecular level","volume":"37","author":"Sadek","year":"2018","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_5","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-\u03b21\/Smad3 pathway. Molecules, 23.","DOI":"10.3390\/molecules23010215"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0163-7258(89)90050-8","article-title":"Mechanisms of carbon tetrachloride toxicity","volume":"43","author":"Recknagel","year":"1989","journal-title":"Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/713611034","article-title":"Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model","volume":"33","author":"Weber","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.biopha.2018.02.126","article-title":"In renal hypertension, Cirsium japonicum strengthens cardiac function via the intermedin\/nitric oxide pathway","volume":"101","author":"Yang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.biopha.2017.01.022","article-title":"The hemostatic effect study of Cirsium setosum on regulating \u03b11-ARs via mediating norepinephrine synthesis by enzyme catalysis","volume":"87","author":"Chang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"66","DOI":"10.15430\/JCP.2016.21.1.66","article-title":"Ethanol extract of Cirsium japonicum var. ussuriense Kitamura exhibits the activation of nuclear factor erythroid 2-related factor 2-dependent antioxidant response element and protects human keratinocyte HaCaT cells against oxidative DNA damage","volume":"21","author":"Yoo","year":"2016","journal-title":"J. Cancer Prev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1039\/C6FO00068A","article-title":"Hepatoprotective effect of flavonoids from Cirsium japonicum DC on hepatotoxicity in comparison with silymarin","volume":"7","author":"Ma","year":"2016","journal-title":"Food Funct."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1080\/14786419.2015.1084304","article-title":"Hepatoprotective phenylethanoid glycosides from Cirsium setosum","volume":"30","author":"Ma","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3892\/etm.2014.1698","article-title":"Ethanol extract of Cirsium japonicum attenuates hepatic lipid accumulation via AMPK activation in human HepG2 cells","volume":"8","author":"Wan","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s12272-013-0229-9","article-title":"Luteolin mediates the antidepressant-like effects of Cirsium japonicum in mice, possibly through modulation of the GABAA receptor","volume":"37","author":"Kim","year":"2014","journal-title":"Arch. Pharm. Res."},{"key":"ref_15","first-page":"18","article-title":"The ethanol extract of Cirsium japonicum increased chloride ion influx through stimulating GABAA receptor in human neuroblastoma cells and exhibited anxiolytic-like effects in mice","volume":"7","author":"Lee","year":"2013","journal-title":"Drug Discov. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.4162\/nrp.2008.2.4.247","article-title":"Antioxidant and antidiabetic activities of extracts from Cirsium japonicum roots","volume":"2","author":"Yin","year":"2008","journal-title":"Nutr. Res. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.2165\/00063030-200115070-00005","article-title":"Silymarin: A review of its clinical properties in the management of hepatic disorders","volume":"15","author":"Wellington","year":"2001","journal-title":"BioDrugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.2165\/00003495-200161140-00003","article-title":"The use of silymarin in the treatment of liver diseases","volume":"61","author":"Saller","year":"2001","journal-title":"Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s12020-012-9677-0","article-title":"Anti-oxidant therapy in non-alcoholic fatty liver disease: The role of silymarin","volume":"42","author":"Abenavoli","year":"2012","journal-title":"Endocrine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/00004836-200310000-00013","article-title":"Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons","volume":"37","author":"Lieber","year":"2003","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_21","first-page":"903","article-title":"Cirsium","volume":"Volume 4","author":"Huang","year":"2000","journal-title":"Flora of Taiwan"},{"key":"ref_22","first-page":"951","article-title":"Triterpene compounds from Cirsium setosum","volume":"37","author":"Li","year":"2012","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/pca.846","article-title":"Differentiation of Cirsium japonicum and C. setosum by TLC and HPLC-MS","volume":"16","author":"Ganzera","year":"2005","journal-title":"Phytochem. Anal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1080\/10286020.2016.1194831","article-title":"Cytotoxic phenylpropanoid glycosides from Cirsium japonicum","volume":"18","author":"Shang","year":"2016","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1021\/np500233t","article-title":"Bioactive constituents of Cirsium japonicum var. australe","volume":"77","author":"Lai","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"215","DOI":"10.7150\/thno.7868","article-title":"Quantitative liver-specific protein fingerprint in blood: A signature for hepatotoxicity","volume":"4","author":"Hu","year":"2014","journal-title":"Theranostics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1142\/S0192415X08005825","article-title":"Hepatoprotective effect of Cirsium arisanense Kitamura in tacrine-treated hepatoma Hep 3B cells and C57BL mice","volume":"36","author":"Ku","year":"2008","journal-title":"Am. J. Chin. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.foodchem.2011.01.041","article-title":"Evaluation of the antioxidant activity of five endemic Ligustrum species leaves from Taiwan flora in vitro","volume":"127","author":"Wu","year":"2011","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1530-0277.2006.00063.x","article-title":"Silymarin protects against acute ethanol-induced hepatotoxicity in mice","volume":"30","author":"Song","year":"2006","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1016\/0006-2952(90)90625-U","article-title":"Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant","volume":"39","author":"Letteron","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"ref_32","first-page":"193","article-title":"A review of the bioavailability and clinical efficacy of milk thistle phytosome: A silybin-phosphatidylcholine complex (Siliphos)","volume":"10","author":"Kidd","year":"2005","journal-title":"Altern. Med. Rev."},{"key":"ref_33","first-page":"160","article-title":"Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside","volume":"15","author":"Arauz","year":"2016","journal-title":"Ann. Hepatol."},{"key":"ref_34","first-page":"121","article-title":"Free radicals in tissue damage in liver diseases and therapeutic approach","volume":"11 Suppl","author":"Feher","year":"1986","journal-title":"Tokai J. Exp. Clin. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7369","DOI":"10.1038\/sj.onc.1206940","article-title":"The role of glutathione-S-transferase in anti-cancer drug resistance","volume":"22","author":"Townsend","year":"2003","journal-title":"Oncogene"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1089\/ars.2011.3999","article-title":"Superoxide dismutases: Role in redox signaling, vascular function, and diseases","volume":"15","author":"Fukai","year":"2011","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1152\/physrev.00061.2009","article-title":"Hepatocyte death: A clear and present danger","volume":"90","author":"Malhi","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2017.08.020","article-title":"Effects of diosmetin on nine cytochrome P450 isoforms, UGTs and three drug transporters in vitro","volume":"334","author":"Chen","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30723","DOI":"10.18632\/oncotarget.15413","article-title":"Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice","volume":"8","author":"Yang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.bbrc.2012.05.022","article-title":"Protective effect of l-theanine on carbon tetrachloride-induced acute liver injury in mice","volume":"422","author":"Jiang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1039\/C4FO00219A","article-title":"Protective effects of Drynaria fortunei against 6-hydroxydopamine-induced oxidative damage in B35 cells via the PI3K\/AKT pathway","volume":"5","author":"Kuo","year":"2014","journal-title":"Food Funct."},{"key":"ref_42","first-page":"124","article-title":"Extraction of silymarin from milk thistle (Silybum marianum) seeds\u2014A comparison of conventional and microwave-assisted extraction methods","volume":"51","author":"Saleh","year":"2017","journal-title":"J. Microw. Power Electromagn. Energy"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/5\/1329\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:02:41Z","timestamp":1760194961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/5\/1329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,30]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["ijms19051329"],"URL":"https:\/\/doi.org\/10.3390\/ijms19051329","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,30]]}}}