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 cellula...
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| Published in | Toxicology (Amsterdam) Vol. 197; no. 3; pp. 239 - 251 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
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Elsevier Ireland Ltd
03.05.2004
Amsterdam Elsevier Science |
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| Abstract | 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
μM Cd. Also, GRE effectively blocked Cd (1
μM)-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
μM) or Cd (0.3–1
μM) + 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. |
|---|---|
| AbstractList | 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. 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 μM Cd. Also, GRE effectively blocked Cd (1 μM)-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 μM) or Cd (0.3–1 μM) + 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. |
| Author | Kim, Chul Young Byun, Sung Hui Kim, Sang Geon Kim, Sang Chan Yang, Chae Ha Kim, Jin Woong |
| Author_xml | – sequence: 1 givenname: Sang Chan surname: Kim fullname: Kim, Sang Chan organization: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea – sequence: 2 givenname: Sung Hui surname: Byun fullname: Byun, Sung Hui organization: College of Oriental Medicine, Research Center for Biomedical Resources of Oriental Medicine, Daegu Hanny University, Daegu 706-060, South Korea – sequence: 3 givenname: Chae Ha surname: Yang fullname: Yang, Chae Ha organization: College of Oriental Medicine, Research Center for Biomedical Resources of Oriental Medicine, Daegu Hanny University, Daegu 706-060, South Korea – sequence: 4 givenname: Chul Young surname: Kim fullname: Kim, Chul Young organization: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea – sequence: 5 givenname: Jin Woong surname: Kim fullname: Kim, Jin Woong organization: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea – sequence: 6 givenname: Sang Geon surname: Kim fullname: Kim, Sang Geon email: sgk@snu.ac.kr organization: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea |
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| Keywords | Cd Cadmium MEM Bad Liquiritigenin Glycyrrhizae radix PARP GRE MTT GSH BSO Apoptosis Translocation Toxicity Extract Heavy metal Medicinal plant Cytochrome c Prevention Leguminosae Dicotyledones Angiospermae Plant origin Cytogenetics Cleavage Spermatophyta |
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| SubjectTerms | Animals Apoptosis Bad bcl-Associated Death Protein bcl-X Protein Biological and medical sciences Cadmium Cadmium Chloride - toxicity Carrier Proteins - metabolism Cell Line Cell Survival - drug effects Chemical and industrial products toxicology. Toxic occupational diseases Cytochromes c - metabolism Cytoprotection - drug effects Flavanones Flavonoids - isolation & purification Flavonoids - pharmacology Glycyrrhiza - chemistry Glycyrrhizae radix Hepatocytes - drug effects Hepatocytes - enzymology Hepatocytes - metabolism Liquiritigenin Medical sciences Metals and various inorganic compounds Mitochondria, Liver - drug effects Mitochondria, Liver - enzymology Mitochondria, Liver - metabolism Plant Extracts - isolation & purification Plant Extracts - pharmacology Poly(ADP-ribose) Polymerases - metabolism Proto-Oncogene Proteins c-bcl-2 - metabolism Rats Toxicology |
| Title | 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) |
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