Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice.
OBJECTIVE
Although Artemisia sacrorum Ledeb. (Compositae) has long been used as one kind of oriental folk medicine to treat some liver diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. This study was designed to investigate the hepatoprotective effects of 50% ethanol eluate precipitation of Artemisia sacrorum Ledeb. (EEP) on acetaminophen (APAP)-induced toxicity in mice.


METHODS
The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-alpha) levels in mouse sera, and glutathione (GSH), malondialdehyde (MDA) in mouse liver tissues were measured. In addition, apoptosis and necrosis were evaluated by liver histopathological analysis and DNA laddering. Moreover, caspase-3 and -8 protein expressions in mouse livers were observed by Western blot analysis.


RESULTS
Pretreated with EEP prior to the administration of APAP significantly prevented the increases of AST, ALT, and TNF-alpha levels in sera, and suppressed the GSH depletion, MDA accumulation in liver tissues markedly. In addition, EEP prevented APAP-induced apoptosis and necrosis, as indicated by liver histopathological analysis, immunohistochemical analysis, and DNA laddering. Furthermore, according to the results from Western blot analysis, EEP decreased APAP-induced caspase-3 and caspase-8 protein expressions in mouse livers markedly.


CONCLUSIONS
All these results suggest that the protective effects of EEP against APAP-induced liver injury may involve mechanisms associated with its inhibitive effects of lipid peroxidation and the down-regulation of TNF-alpha mediated apoptosis. In a word, EEP could be a valuable candidate for further development for prevention and treatment of hepatic injury.
Yuan
Hai-Dan
HD
College of Pharmacy, Yan-Bian University, Yanji, Jilin Province 133000, China.
Jin
Guang-Zhu
GZ
Piao
Guang-Chun
GC
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D019306:Artemisia; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*
D010936:Plant Extracts; D000082:Acetaminophen