Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice
Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice
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DOI：
10.1016/j.fct.2008.01.017
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发表时间：
2008-05-01
影响因子：
4.3
通讯作者：
Jeong, Hye Gwang
中科院分区：
文献类型：
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作者：
Lee, Kyung Jin;Choi, Jae Ho;Jeong, Hye Gwang
本研究旨在探讨桔梗皂苷对四氯化碳（CCl 4）致小鼠肝损伤的保护作用。在CCl 4给药前用CKS预处理显著防止血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶活性的增加和肝脏脂质过氧化形成。此外，CKS防止四氯化碳诱导的细胞凋亡和坏死，所示的肝组织病理学研究和DNA梯状。为探讨Fas/Fas配体（FasL）通路是否参与了四氯化碳（CCl 4）诱导的急性肝损伤，采用Western blotting和ELISA法检测Fas、FasL蛋白和caspase-3、-8活性。CKS可显著降低CCl_4诱导的小鼠肝脏Fas/FasL蛋白表达水平，进而减弱CCl_4诱导的caspase-3，-8活性。此外，CKS保护CCl 4诱导的肝脏谷胱甘肽水平的耗竭。研究了CKS对CCl_4生物激活的主要同工酶CYP2E_1的影响。CKS处理导致苯胺的CYP 2 E1依赖性羟基化显著降低。此外，CKS对FeCl 2-抗坏血酸诱导的肝匀浆脂质过氧化反应和超氧自由基清除活性具有抗氧化作用。提示CKS对CCl 4诱导的急性肝损伤的保护作用可能与其阻断CCl 4介导的CYP 2 E1的生物激活和清除自由基的作用有关，并可能与其对Fas/FasL通路介导的细胞凋亡的保护作用有关。(c)2008爱思唯尔有限公司保留所有权利。
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.