title: Effects of ginsenosides on the expression of cytochrome P450s and transporters involved in cholesterol metabolism.
abstract: An extract from red ginseng (steamed and dried roots of Panax ginseng C.A. Meyer; RGE) has been shown to promote cholesterol metabolism in the liver. We have reported that RGE induced the hepatic expression of cytochrome P450 (CYP)7A1, involved in cholesterol metabolism. Other cholesterol metabolism-related proteins, such as CYP8B1, CYP27A1, multidrug resistance-associated protein (MRP)2, MRP3, and Na(+) taurocholate cotransporting polypeptide (NTCP), are involved in cholesterol metabolism. The purpose of this study was to clarify whether RGE affected mRNA expression of cholesterol metabolism-related CYPs and transporters in the liver of hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed little differences in CYP8B1, CYP27A1, MRP2, MRP3, and NTCP mRNA expression levels between hypercholesterolemic rats with or without RGE treatments. However, the disruption of the membrane localization of MRP2 was suppressed by RGE treatments in hypercholesterolemic rats. In-vitro studies using rat primary hepatocytes showed upregulation of CYP8B1 and MRP2 mRNA by the addition of RGE (100 and 500 μg/mL). We further examined which ginsenosides contributed to the upregulation of CYP8B1 and MRP2 mRNA levels. Ginsenoside Re enhanced the mRNA level of CYP8B1, whereas ginsenosides Rb2 and Rg2 enhanced MRP2 mRNA levels. These results suggest that the in-vitro exposure of hepatocytes to RGE or some ginsenosides could lead to upregulation of CYP8B1 and MRP2, resulting in the alteration of biosynthesis and disposition of bile acids.
authors.affiliation: Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawase
authors.forename: Ayano
authors.initials: A
authors.lastname: Yamada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Gamou
authors.forename: Chika
authors.initials: C
authors.lastname: Tahara
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takeshita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Murata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Samukawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwaki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D036145:Ginsenosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism
chemical_list: D002784:Cholesterol; D003577:Cytochrome P-450 Enzyme System; D036145:Ginsenosides; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D010936:Plant Extracts; D027981:Symporters; C071908:sodium-bile acid cotransporter