A diterpenoid acanthoic acid from Acanthopanax koreanum protects against D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice.
The hepatoprotective effects of a diterpenoid acanthoic acid isolated from Acanthopanax koreanum NAKAI were evaluated in a D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure mouse model. Mice were pretreated orally with acanthoic acid 12 and 1 h before intraperitoneal injection of D-galactosamine and lipopolysaccharide. Pretreatment with the compound markedly reduced lethal liver injury in experimental animals. The effects were likely associated with a significant decrease in serum tumor necrosis factor (TNF)-alpha levels, which are correlated not only with those of alanine aminotransferase and aspartate aminotransferase but also with the reduced number of apoptotic hepatocytes in the liver as confirmed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay. These results suggest that acanthoic acid protects against D-galactosamine/lipopolysaccharide-induced fulminant liver failure at least in part by a mechanism associated with the down-regulation of TNF-alpha secretion.
Nan
Ji-Xing
JX
Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education and College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China. jjlee@kribb.re.kr
Jin
Xue-Jun
XJ
Lian
Li-Hua
LH
Cai
Xing Fu
XF
Jiang
Ying-Zi
YZ
Jin
Hong Ri
HR
Lee
Jung Joon
JJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D028001:Eleutherococcus / Q000737:chemistry*; D005688:Galactosamine; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018517:Plant Roots / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C099958:acanthoic acid; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase