title: Hepatotoxicity of kaurene glycosides from Xanthium strumarium L. fruits in mice.
abstract: The fruit of Xanthium strumarium L. (Cang-Er-Zi) is a traditional Chinese medicine that is used in curing nasal diseases and headache according to the Chinese Pharmacopoeia. However, clinical utilization of Xanthium strumarium is relatively limited because of its toxicity. The present investigation was carried out to evaluate the toxic effects on acute liver injury in mice of the two kaurene glycosides (atractyloside and carbxyatractyloside), which are main toxic constituents isolated from Fructus Xanthii on acute liver injury in mice. Histopathological examinations revealed that there were not obviously visible injury in lungs, heart, spleen, and the central nervous system in the mice by intraperitoneal injection of atractyloside (ATR, at the doses 50,125 and 200 mg/kg) and carbxyatractyloside (CATR, at the doses 50,100 and 150 mg/kg) for 5 days. However, it revealed extensive liver injuries compared with the normal group. In the determination of enzyme levels in serum, intraperitoneal injection of ATR and CATR resulted in significantly elevated serum alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP) activities compared to controls. In the hepatic oxidative stress level, antioxidant-related enzyme activity assays showed that ATR and CATR administration significantly increased hepatic malondialdehyde (MDA) concentration, as well as decreased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) concentration, and this was in good agreement with the results of serum aminotransferase activity and histopathological examinations. Taken together, our results demonstrate that kaurene glycosides induce hepatotoxicity in mice by way of its induction of oxidative stress as lipid peroxidation in liver, which merited further studies. Therefore, these toxic constituents explain, at least in part, the hepatotoxicity of X. strumarium L. in traditional medicine.
authors.affiliation: Department of Pharmacognosyl, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Xue
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.forename: Qiao-Yan
authors.initials: QY
authors.lastname: Zhang
authors.forename: Bao-Kang
authors.initials: BK
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Qian-Liang
authors.initials: QL
authors.lastname: Ming
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Qin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001278:Atractyloside / Q000031:analogs & derivatives / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D045786:Diterpenes, Kaurane / Q000633:toxicity*; D005260:Female; D005638:Fruit / Q000737:chemistry* / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism; D006027:Glycosides / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D031210:Xanthium / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D045786:Diterpenes, Kaurane; D006027:Glycosides; D001278:Atractyloside; C002627:kaurene; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C003853:carboxyatractyloside