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 DGalN/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.