Protective effect of wedelolactone against CCl sub(4)-induced acute liver injury in mice

• Published in: International immunopharmacology 2016-05, Vol.34, p.44-52
• Main Authors: Lua, Yang, Hua, DongMei, Mab, ShanBo, Zhaoa, Xian, Wanga, Shan, Weia, Guo, Wangb, XiFang, Wena, AiDong, Wanga, JingWen
• Format: Article
• Language: English
• Subjects: Eclipta
• ISSN: 1567-5769
• DOI: 10.1016/j.intimp.2016.02.003

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 CCl sub(4)-induced acute liver injury (ALI). Our data showed that WEL markedly decreased the CCl sub(4)-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- alpha , IL-1 beta 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- Kappa B p65 from cytoplasm to nucleus and enhanced the phosphorylation of c-Jun. N-terminal kinase (JNK). Moreover, results showed that WEL significantly inhibited CCl sub(4)-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 CCl sub(4)-induced ALI in mice by enhancing the antioxidative defense system, suppressing the inflammatory response and cell apoptosis of liver.