Walnut polyphenols prevent liver damage induced by carbon tetrachloride and D-galactosamine: Hepatoprotective hydrolyzable tannins in the kernel pellicles of walnut

The polyphenol-rich fraction (WP, 45% polyphenol) prepared from the kernel pellicles of walnuts was assessed for its hepatoprotective effect in mice. A single oral administration of WP (200 mg/kg) significantly suppressed serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) elevation in liver injury induced by carbon tetrachloride (CCl₄), while it did not suppress D-galactosamine (GalN)-induced liver injury. In order to identify the active principles in WP, we examined individual constituents for the protective effect on cell damage induced by CCl₄ and D-GalN in primary cultured rat hepatocytes. WP was effective against both CCl₄- and D-GalN-induced hepatocyte damages. Among the constituents, only ellagitannins with a galloylated glucopyranose core, such as tellimagrandins I, II, and rugosin C, suppressed CCl₄-induced hepatocyte damage significantly. Most of the ellagitannins including tellimagrandin I and 2,3-O-hexahydroxydiphenoyl-glucose exhibited remarkable inhibitory effect against D-GalN-induced damage. Telliamgrandin I especially completely suppressed both CCl₄- and D-GalN-induced cell damage, and thus is likely the principal constituent for the hepatoprotective effect of WP.