Cytoprotective effects of Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage).
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.
Kim
Sang Chan
SC
College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Byun
Sung Hui
SH
Yang
Chae Ha
CH
Kim
Chul Young
CY
Kim
Jin Woong
JW
Kim
Sang Geon
SG
D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D044950:Flavanones; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C494821:Bad protein, rat; C494813:Bcl2l1 protein, rat; D002352:Carrier Proteins; D044950:Flavanones; D005419:Flavonoids; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D019256:Cadmium Chloride; C083152:liquiritigenin