title: Protective mechanism of andrographolide against carbon tetrachloride-induced acute liver injury in mice.
abstract: The aim of this study was to investigate the protective effects of andrographolide (AP), a bioactive component isolated from Andrographis paniculata, on carbon tetrachloride (CCl(4))-induced liver injury as well as the possible mechanisms involved in this protection in mice. Acute liver injury was induced by CCl(4) intoxication in mice. Serum biological analysis, lipid peroxides and antioxidant estimation, histopathological studies, reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were carried out. CCl(4) treatment resulted in severe hepatic injury, as evidenced by significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and typical histopathological changes, such as hepatocyte necrosis. Additionally, CCl(4) administration led to oxidative stress in mice, as indicated by a remarkable increase in the hepatic malondialdehyde (MDA) level, together with a significant decrease in liver reduced glutathione (GSH) content. However, CCl(4)-induced hepatotoxicity was significantly attenuated by pretreatment with AP, as demonstrated by significant reduction of serum ALT, AST levels and hepatic MDA activity, along with a remarkable increase in hepatic GSH content. Histopathological changes induced by CCl(4) were also ameliorated by AP pretreatment. The marked increase of tumor necrosis factor-α (TNF-α) induced by CCl(4) was attenuated by AP, and the dramatic elevation of heme oxygenase-1 (HO-1) at transcriptional and protein levels was augmented following AP pretreatment. AP can effectively prevent liver injury induced by CCl(4), which may be due to inhibition of oxidative stress and inflammatory responses.
authors: Experimental Teaching Center of Preventive Medicine, School of Public Health and Tropical Medicine, Southern Medical University, P.R. China.
authors: Ju-Feng
authors: JF
authors: Ye
authors: Hang
authors: H
authors: Zhu
authors: Zhi-Feng
authors: ZF
authors: Zhou
authors: Ri-Bo
authors: RB
authors: Xiong
authors: Xi-Wen
authors: XW
authors: Wang
authors: Li-Xian
authors: LX
authors: Su
authors: Bing-De
authors: BD
authors: Luo
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004224:Diterpenes; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C030419:andrographolide; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione