Gentiana manshurica Kitagawa prevents acetaminophen-induced acute hepatic injury in mice via inhibiting JNK/ERK MAPK pathway.
OBJECTIVE
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.


CONCLUSIONS
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.
Wang
Ai-Yan
AY
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.
Lian
Li-Hua
LH
Jiang
Ying-Zi
YZ
Wu
Yan-Ling
YL
Nan
Ji-Xing
JX
D000082:Acetaminophen / Q000009:adverse effects* / Q000494:pharmacology; D000410:Alanine Transaminase / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D030012:Gentiana; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction / Q000502:physiology
D000447:Aldehydes; D061945:Caspase Inhibitors; D004365:Drugs, Chinese Herbal; D000082:Acetaminophen; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D053148:Caspase 3; D005978:Glutathione; C027576:4-hydroxy-2-nonenal