Hepatoprotective Effect of Taxiresinol and (7′R)-7′-Hydroxylariciresinol on D-Galactosamine and Lipopolysaccharide-Induced Liver Injury in Mice

Abstract

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-α) 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-α-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-α production by activated macrophages and a direct inhibition of apoptosis induced by TNF-α in D-GalN/LPS-treated mice.

Key words

Taxiresinol - (7′R)-7′-hydroxylariciresinol - apoptosis - hepatoprotective effect - Taxus yunnanensis - Taxaceae - lignans

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