Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice.
The protective effect of a diterpenoid acanthoic acid (AA) isolated from Acanthopanax koreanum Nakai was investigated in acetaminophen (APAP)-induced hepatic toxicity. Drug-induced hepatotoxicity induced by an intraperitoneal (i.p.) injection of 300mg/kg (sub-lethal dose) of APAP. Pretreatment with AA (50 and 100mg/kg) orally 2h before the APAP administration attenuated the APAP-induced acute increase in serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activites, replenished the depleted hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities, decreased malondialdehyde (MDA) level and considerably reduced the histopathological alterations in a manner similar to silymarin (Sily). Immunohistochemical analyses also demonstrated that AA could reduce the appearance of necrosis regions as well as caspase-3 and hypoxia inducible factor-1alpha (HIF-1alpha) expression in liver tissue. Our results indicated that AA protected liver tissue from the oxidative stress elicites by APAP-induced liver damage and suggestes that the hepatic protection mechanism of AA would relate to antioxidation and hypoxia factor on APAP-induced hepatotoxicity.
Wu
Yan-Ling
YL
Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002 Jilin Province, China.
Jiang
Ying-Zi
YZ
Jin
Xue-Jun
XJ
Lian
Li-Hua
LH
Piao
Juan-Yu
JY
Wan
Ying
Y
Jin
Hong-Ri
HR
Joon Lee
Jung
J
Nan
Ji-Xing
JX
D000082:Acetaminophen; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D028001:Eleutherococcus / Q000737:chemistry*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots
D000975:Antioxidants; D004224:Diterpenes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; C099958:acanthoic acid; D000082:Acetaminophen; D008315:Malondialdehyde; D053148:Caspase 3