title: Protective effect of wedelolactone against CCl4-induced acute liver injury in mice.
abstract: Eclipta, a traditional Chinese medicine, has been used to treat liver disease for centuries. However, the chemical basis and biological mechanisms of Eclipta remain elusive. The current study aims to investigate the hepatoprotective effect of wedelolactone (WEL), a major coumarin in Eclipta, using C57BL/6 mice with carbon tetrachloride CCl4-induced acute liver injury (ALI). Our data showed that WEL markedly decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and improved hepatic histopathology changes. WEL also significantly decreased the content of MDA in liver tissues, meanwhile increased the activities of antioxidant enzymes SOD and GSH-Px. In addition, WEL reduced the protein expression of TNF-α, IL-1β and IL-6, as well as mRNA expression. Western blot results revealed that WEL repressed phosphorylation of extracellular signal-regulated kinase (ERK) and translocation of NF-κB p65 from cytoplasm to nucleus and enhanced the phosphorylation of c-Jun. N-terminal kinase (JNK). Moreover, results showed that WEL significantly inhibited CCl4-induced hepatocytes apoptosis, markedly suppressed the down-regulation of Bax and active Caspase-3 expression and accelerated the expression of Bcl-2. Overall, the findings indicate that WEL exhibits a protective effect against CCl4-induced ALI in mice by enhancing the antioxidative defense system, suppressing the inflammatory response and cell apoptosis of liver.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Shaanxi University of Traditional Chinese Medicine, Xian Yang 712046, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: DongMei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Shaanxi University of Traditional Chinese Medicine, Xian Yang 712046, China.
authors.forename: ShanBo
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: Shaanxi University of Traditional Chinese Medicine, Xian Yang 712046, China.
authors.forename: XiFang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: AiDong
authors.initials: A
authors.lastname: Wen
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: wangjingwen8021@163.com.
authors.forename: JingWen
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000517:prevention & control*; D003374:Coumarins / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D036601:Eclipta / Q000276:immunology; D006505:Hepatitis / Q000276:immunology / Q000517:prevention & control*; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D003374:Coumarins; D016207:Cytokines; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; C051122:wedelolactone; D002251:Carbon Tetrachloride; D000072105:Superoxide Dismutase-1
keywords: Acute liver injury; Apoptosis; Hepatoprotective action; Inflammatory response; Oxidative stress; Wedelolactone