Brief Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Jan 21, 2010; 16(3): 384-391
Published online Jan 21, 2010. doi: 10.3748/wjg.v16.i3.384
Gentiana manshurica Kitagawa prevents acetaminophen-induced acute hepatic injury in mice via inhibiting JNK/ERK MAPK pathway
Ai-Yan Wang, Li-Hua Lian, Ying-Zi Jiang, Yan-Ling Wu, Ji-Xing Nan
Ai-Yan Wang, Li-Hua Lian, Ying-Zi Jiang, Yan-Ling Wu, Ji-Xing Nan, Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China
Author contributions: Wang AY and Lian LH contributed equally to this work; Wang AY, Lian LH and Nan JX designed the research; Wang AY, Lian LH, Jiang YZ and Wu YL preformed the research; Lian LH and Nan JX wrote the paper.
Supported by National Natural Science Foundation of China, No. 30660225 and No. 30960511
Correspondence to: Ji-Xing Nan, Professor, Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China. jxnanybu@gmail.com
Telephone: +86-433-2660603 Fax: +86-433-2660631
Received: October 23, 2009
Revised: December 4, 2009
Accepted: December 11, 2009
Published online: January 21, 2010
Abstract

AIM: To investigate the in vivo hepatoprotective effects and mechanisms of Gentiana manshurica Kitagawa (GM) in acetaminophen (APAP)-induced liver injury in mice.

METHODS: GM (200, 150 or 50 mg/kg body weight) or N-acetyl-L-cysteine (NAC; 300 mg/kg body weight) was administrated orally with a single dose 2 h prior to APAP (300 mg/kg body weight) injection in mice.

RESULTS: APAP treatment significantly depleted hepatic glutathione (GSH), increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malonyldialdehyde (MDA) and 4-hydroxynonenal levels, and decreased hepatic activity of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD). However, the pretreatment of GM significantly alleviated APAP-induced oxidative stress by increasing GSH content, decreasing serum ALT, AST and MDA, and retaining the activity of GSH-px and SOD in the liver. Furthermore, GM pretreatment can inhibit caspase-3 activation and phosphorylation of c-Jun-NH2-terminal protein kinase 2 (JNK1/2) and extracellular signal-regulated kinase (ERK). GM also remarkably attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling method.

CONCLUSION: Hepatoprotective effects of GM against APAP-induced acute toxicity are mediated either by preventing the decline of hepatic antioxidant status or its direct anti-apoptosis capacity. These results support that GM is a potent hepatoprotective agent.

Keywords: Gentiana manshurica Kitagawa, Acetaminophen, Oxidative stress, Caspase-3, JNK/ERK MAPK