The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs.
Wild Panax ginseng C.A. Meyer (WG) is a well-known medicinal herb. In this study, the protective effects of a water extract from the root of WG on benzo[alpha]pyrene (BP)-induced hepatotoxicity and the mechanism of these effects were investigated for the first time. The effects of WG on liver toxicities induced by BP were assessed by blood biochemical and histopathological analyses. BP caused severe liver injury in rats, as indicated by elevated plasma ALT, AST and LPO levels. Pretreatment with WG for 4 weeks completely abrogated increases in the ALT, AST and LPO levels when challenged with BP. Reductions in GSH content and GST activity by BP were reversed by WG. These protective effects of WG against BP-induced toxicity were consistent with the results of histopathological examinations. We next examined the effects of WG on the gene expression of the enzymes that metabolize BP in H4IIE cells. CYP1A1 mRNA and protein expression were increased by BP. WG moderately inhibited BP-induced CYP1A1 gene expression. Moreover, GSTA2, GSTA3 and GSTM2 gene expressions were significantly increased by WG through the Nrf2/antioxidant responsive element pathway for enzyme induction. In summary, WG is efficacious in protecting against BP-induced hepatotoxicity as results of metabolic regulations through both the inhibition of metabolic enzyme activation and the enhancement of electrophilic detoxification, implying that WG should be considered a potential chemopreventive agent.
Gum
Sang Il
SI
College of Oriental Medicine and Research Institute of Oriental Medicine, Dongguk University, Kyungju 780-714, Republic of Korea.
Jo
Sung Jun
SJ
Ahn
Sang Hyun
SH
Kim
Sang Geon
SG
Kim
Jin-Taek
JT
Shin
Heung Mook
HM
Cho
Min Kyung
MK
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity; D015153:Blotting, Western; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000517:prevention & control*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D010936:Plant Extracts; D012333:RNA, Messenger; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2; C119995:glutathione S-transferase alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase