Saponins isolated from the root of Platycodon grandiflorum protect against acute ethanol-induced hepatotoxicity in mice.
The protective effects of saponins isolated from the root of Platycodon grandiflorum (Changkil saponins: CKS) against alcoholic steatosis in liver injury induced by acute ethanol administration were investigated. Pretreatment with CKS prior to ethanol administration significantly prevented the increases in serum alanine aminotransferase activity, hepatic TNF-alpha level, hepatic lipid peroxidation and hepatic triglyceride level. CKS prevented ethanol-induced steatosis and necrosis, as indicated by liver histopathological studies. Additionally, CKS protected against ethanol-induced depletion of hepatic glutathione levels. CYP2E1 has been suggested as a major contributor to ethanol-induced oxidative stress and liver injury. The concurrent administration of CKS efficaciously abrogated the CYP2E1 induction and CYP2E1-dependents hydroxylation of aniline as compared to the individual treatment at higher doses. These findings suggest that CKS may prevent ethanol-induced acute liver injury, possibly through its ability to block CYP2El-mediated ethanol bioactivation and its free radical scavenging effects.
Khanal
Tilak
T
BK 21 Project Team, Department of Pharmacy, College of Pharmacy, Chosun University, 375 Seosuk-dong, Gwangju 501-759, Republic of Korea.
Choi
Jae Ho
JH
Hwang
Yong Pil
YP
Chung
Young Chul
YC
Jeong
Hye Gwang
HG
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000378:metabolism; D004790:Enzyme Induction; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006900:Hydroxylation; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D031238:Platycodon / Q000737:chemistry*; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012503:Saponins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D000410:Alanine Transaminase; D005978:Glutathione