Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice.
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 (CCl(4))-induced hepatotoxicities in mice. Pretreatment with CKS prior to the administration of CCl(4) significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities and hepatic lipid peroxidation formation. In addition, CKS prevented CCl(4)-induced apoptosis and necrosis, as indicated by a liver histopathologic study and DNA laddering. To determine whether Fas/Fas ligand (FasL) pathway involved in CCl(4)-induced acute liver injury, Fas and FasL proteins and caspase-3, -8 activities were tested by western blotting and ELISA. CKS markedly decreased CCl(4)-induced Fas/FasL protein expression levels and in turn attenuated CCl(4)-induced caspase-3, -8 activities in mouse livers. Additionally, CKS protected the CCl(4)-induced depletion of hepatic glutathione levels. The effect of CKS on CYP2E1, the major isozyme involved in CCl(4) 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 FeCl(2)-ascorbate induced lipid peroxidation in liver homogenates, and on superoxide radical scavenging activity. These findings suggest that the protective effects of CKS against CCl(4)-induced acute liver injury possibly involve mechanisms related to its ability to block CYP2El-mediated CCl(4) bioactivation and its free radical scavenging effects, and that is also protects against Fas/FasL pathway mediated apoptosis.
Lee
Kyung Jin
KJ
BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Gwangju, South Korea.
Choi
Jae Ho
JH
Kim
Hyung Gyun
HG
Han
Eun Hee
EH
Hwang
Yong Pil
YP
Lee
Young Chun
YC
Chung
Young Chul
YC
Jeong
Hye Gwang
HG
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D029422:Campanulaceae / Q000737:chemistry*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology*; D002712:Chlorides; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000096:biosynthesis; D005290:Ferric Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012503:Saponins / Q000032:analysis / Q000627:therapeutic use*
D002712:Chlorides; D053222:Fas Ligand Protein; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D012503:Saponins; D004247:DNA; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione; D001205:Ascorbic Acid; C024555:ferric chloride