title: Increased effects of ginsenosides on the expression of cholesterol 7α-hydroxylase but not the bile salt export pump are 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 have various actions on physiological functions. The mechanisms by which RGE promotes cholesterol metabolism in the liver are unclear, but RGE decreases the plasma levels of cholesterol. We investigated whether RGE affected the mRNA expression of cholesterol metabolism-related proteins such as cytochrome P450 (CYP)7A1 and bile salt export pump (BSEP) in the liver in hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed the upregulation of CYP7A1 mRNA in hypercholesterolemic rats treated with RGE. Treatment with RGE exhibited decreased ratios of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol compared with hypercholesterolemia without RGE. In-vitro studies also showed the upregulation of CYP7A1 mRNA and protein levels by the addition of RGE to rat primary hepatocytes. The mRNA levels of BSEP exhibited few changes. The sustained levels of the liver X receptor (LXR) in vivo and the increased levels of LXR in vitro on RGE treatment could be involved in the upregulation of CYP7A1. To clarify the effects of 11 ginsenosides including RGE on the mRNA levels of CYP7A1 and BSEP, we performed in-vitro experiments using rat primary hepatocytes. The ginsenosides Ro, Rg3, Re, Rg1, and Rg2 exhibited increased mRNA levels of CYP7A1. These results suggest that several ginsenosides including RGE promoted cholesterol metabolism due to upregulation of CYP7A1.
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: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000187:drug effects / Q000378:metabolism; D005894:Panax / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots; D010946:Plants, Medicinal; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490548:Abcb11 protein, rat; D000924:Anticholesteremic Agents; D036145:Ginsenosides; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010936:Plant Extracts; D012333:RNA, Messenger; D002784:Cholesterol; C532838:CYP7A1 protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase