Hepatoprotective effect of taxiresinol and (7'R)-7'-hydroxylariciresinol on D-galactosamine and lipopolysaccharide-induced liver injury in mice.
The hepatoprotective effect of taxiresinol ( 1) and (7' R)-7'-hydroxylariciresinol ( 2), two tetrahydrofuran-type lignans isolated from the wood of Taxus yunnanensis, were investigated on D-galactosamine ( D-GalN)/lipopolysaccharide (LPS)-induced hepatic liver injury in mice. Pre-administration of 1 or 2 at doses of 50 and 10 mg/kg ( i. p.) at 12 and 1 h before D-GalN/LPS injection significantly inhibited hepatocyte DNA fragmentation and apoptotic body formation. Pre-treatment of these two lignans further suppressed hepatic necrosis which occur at later stage of D-GalN/LPS intoxication as demonstrated by the significant and dose-dependent reduction in serum glutamic pyruvic transaminase (sGPT) and serum glutamic oxaloacetic transaminase (sGOT) at 8 h after intoxication. The elevation of serum tumor necrosis factor-alpha (TNF- alpha) level by D-GalN/LPS toxication was significantly inhibited by 1 or 2 at doses of 50 and 10 mg/kg. Moreover, both of these lignans significantly protected hepatocytes from D-GalN/TNF- alpha-induced cell death in primary cultured mouse hepatocytes. These results suggested that 1 and 2 had protected the hepatocytes from apoptosis via an inhibition of TNF- alpha production by activated macrophages and a direct inhibition of apoptosis induced by TNF- alpha in D-GalN/LPS-treated mice.
Nguyen
Nhan Trung
NT
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
Banskota
Arjun H
AH
Tezuka
Yasuhiro
Y
Le Tran
Quan
Q
Nobukawa
Takahiro
T
Kurashige
Youichi
Y
Sasahara
Masakiyo
M
Kadota
Shigetoshi
S
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005688:Galactosamine; D017705:Lignans; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010946:Plants, Medicinal; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014197:Trees
D005663:Furans; D017705:Lignans; D008070:Lipopolysaccharides; D010936:Plant Extracts; D020011:Protective Agents; C483062:taxiresinol; D005688:Galactosamine