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

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• 作者：Kyung Jin Lee ; Jae Ho Choi ; Hyung Gyun Kim ; Eun Hee Han ; Yong Pil Hwang ; Young Chun Lee ; Young Chul Chung ; Hye Gwang Jeong
• 关键词：Platycodon grandiflorum ; Carbon tetrachloride ; Hepatotoxicity ; Fas/FasL pathway ; CYP2E1
• 刊名：Food and Chemical Toxicology
• 出版年：2008
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：May 2008
• 卷：46
• 期：5
• 页码：1778-1785
• 文件大小：488 K

摘要

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 CYP2El-mediated CCl₄ bioactivation and its free radical scavenging effects, and that is also protects against Fas/FasL pathway mediated apoptosis.