Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice

The purpose of this study was to investigate the protective effects of the saponins isolated from the root of Platycodi Radix (Changkil saponins: CKS) on carbon tetrachloride (CCl4)-induced hepatotoxicities in mice. Pretreatment with CKS prior to the administration of CCl4 significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities and hepatic lipid peroxidation formation. In addition, CKS prevented CCl4-induced apoptosis and necrosis, as indicated by a liver histopathologic study and DNA laddering. To determine whether Fas/Fas ligand (FasL) pathway involved in CCl4-induced acute liver injury, Fas and FasL proteins and caspase-3, -8 activities were tested by western blotting and ELISA. CKS markedly decreased CCl4-induced Fas/FasL protein expression levels and in turn attenuated CCl4-induced caspase-3, -8 activities in mouse livers. Additionally, CKS protected the CCl4-induced depletion of hepatic glutathione levels. The effect of CKS on CYP2E1, the major isozyme involved in CCl4 bioactivation, was investigated. Treatment with CKS resulted in a significant decrease in the CYP2E1-dependent hydroxylation of aniline. In addition, CKS exhibited antioxidant effects on FeCl2-ascorbate induced lipid peroxidation in liver homogenates, and on superoxide radical scavenging activity. These findings suggest that the protective effects of CKS against CCl4-induced acute liver injury possibly involve mechanisms related to its ability to block CYP2E1-mediated CCl4 bioactivation and its free radical scavenging effects, and that is also protects against Fas/FasL pathway mediated apoptosis. (c) 2008 Elsevier Ltd. All rights reserved.