Kim Sang Chan, Byun Sung Hui, Yang Chae Ha, Kim Chul Young, Kim Jin Woong, Kim Sang Geon
College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Toxicology. 2004 May 3;197(3):239-51. doi: 10.1016/j.tox.2004.01.010.
Glycyrrhizae radix has been popularly used as one of the oldest and most frequently employed botanicals in herbal medicine in Asian countries, and currently occupies an important place in food products. Cadmium (Cd) induces both apoptotic and non-apoptotic cell death, in which alterations in cellular sulfhydryls participate. In the present study, we determined the effects of G. radix extract (GRE) and its representative active components on cell death induced by Cd and explored the mechanistic basis of cytoprotective effects of G. radix. Incubation of H4IIE cells with GRE inhibited cell death induced by 10 microM Cd. Also, GRE effectively blocked Cd (1 microM)-induced cell death potentiated by buthionine sulfoximine (BSO) without restoration of cellular GSH. GRE prevented both apoptotic and non-apoptotic cell injury induced by Cd (10 microM) or Cd (0.3-1 microM) + BSO. Inhibition of Cd-induced cell injury by pretreatment of cells with GRE suggested that the cytoprotective effect result from alterations in the levels of the protein(s) responsible for cell viability. GRE inhibited mitochondrial Bad translocation by Cd or CD+BSO, and caused restoration of mitochondrial Bcl(xL) and cytochrome c levels. Cd-induced poly(ADP-ribose)polymerase cleavage in control cells or in cells deprived of sulfhydryls was prevented by GRE treatment. Among the major components present in GRE, liquiritigenin, but not liquiritin, isoliquiritigenin or glycyrrhizin, exerted cytoprotective effect. These results demonstrated that GRE blocked Cd-induced cell death by inhibiting the apoptotic processes involving translocation of Bad into mitochondria, decreases in mitochondrial Bcl(xL) and cytochrome c, and poly(ADP-ribose)polymerase cleavage.
甘草根作为亚洲国家草药医学中最古老且最常用的植物药之一，一直广受欢迎，目前在食品中也占据重要地位。镉（Cd）可诱导凋亡性和非凋亡性细胞死亡，其中细胞巯基的改变参与其中。在本研究中，我们测定了甘草根提取物（GRE）及其代表性活性成分对Cd诱导的细胞死亡的影响，并探讨了甘草根细胞保护作用的机制基础。用GRE孵育H4IIE细胞可抑制10微摩尔Cd诱导的细胞死亡。此外，GRE有效地阻断了丁硫氨酸亚砜胺（BSO）增强的1微摩尔Cd诱导的细胞死亡，而细胞内谷胱甘肽（GSH）并未恢复。GRE可预防10微摩尔Cd或0.3 - 1微摩尔Cd + BSO诱导的凋亡性和非凋亡性细胞损伤。用GRE预处理细胞对Cd诱导的细胞损伤的抑制作用表明，细胞保护作用是由负责细胞活力的蛋白质水平的改变所致。GRE可抑制Cd或Cd + BSO诱导的线粒体Bad转位，并使线粒体Bcl(xL)和细胞色素c水平恢复。GRE处理可防止对照细胞或缺乏巯基的细胞中Cd诱导的聚（ADP - 核糖）聚合酶裂解。在GRE中的主要成分中，甘草素而非甘草苷、异甘草素或甘草酸发挥了细胞保护作用。这些结果表明，GRE通过抑制涉及Bad转位到线粒体、线粒体Bcl(xL)和细胞色素c减少以及聚（ADP - 核糖）聚合酶裂解的凋亡过程，阻断了Cd诱导的细胞死亡。
