Hepatoprotective constituents of the seeds of Combretum quadrangulare

Abstract

Hepatoprotective effect of MeOH, MeOH-H2O (1:1) and H2O extracts of Combretum quadrangulare seeds were examined on D-galactosamine (D-GalN)/tumor necrosis factor-α (TNF-α)-induced cell death in primary cultured mouse hepatocytes. The MeOH extract showed the strongest inhibitory effect on D-GalN/TNF-α-induced cell death (IC50, 56.4 μg/ml). Moreover, the MeOH extract also significantly lowered the serum glutamic pyruvic transaminase (sGPT) level on D-GalN/lipopolysaccharide (LPS)-induced liver injury in mice. Bioguided separation of the MeOH extract led to the isolation of 38 compounds of various classes including triterpene glucosides, lignans and catechin derivatives. Among the isolated triterpene glucosides, lupane-type (1 - 3; IC50, 63.1, 59.8 and 76.2 μM, respectively) and ursane-type (11, mixture of 12 and 14; IC50, 30.2 and 34.6 μM, respectively) compounds exhibited strong hepatoprotective activity. 1-O-Galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl-β-D-glucose (26; IC50, 7.2 μM), methyl gallate (28; IC50, 19.9 μM), and (-)-epicatechin (31; IC50, 71.2 μM) also had a potent hepatoprotective effect on D-GalN/TNF-α-induced cell death in primary cultured mouse hepatocytes.