title: Water extracts of immature Rubus coreanus regulate lipid metabolism in liver cells.
abstract: Hyperlipidemia is a major contributor for atherosclerosis and hypolipidemic drugs such as statin are highly prescribed to treat elevated lipid level in plasma. Rubus coreanus, which is widely cultivated in south eastern Asia, have been reported to show significant cholesterol lowering action in hyperlipidemic subjects. Our objective was to determine the cellular effect of Rubus coreanus extract (RCE) on cholesterol biosynthesis in human hepatic cells (HepG2) and to elucidate the molecular mechanism by which it causes change in cholesterol metabolism. RCE treatment lowered cholesterol biosynthesis as well as secretion from HepG2 cells. This effect was associated with lowering the release of apolipoproteins from hepatic cells. RCE treatment also showed an increase in phosphorylation of foxhead box protein 01 (FoXo-1) and 5-adenosine monophosphate-activated protein kinase (AMPK), thus lowering expression of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase, which might be a major pathway for cholesterol biosynthesis inhibition. Apart from this; RCE also lowered sterol regulatory element-binding protein-1 (SREBP-1) expression in HepG2 cells, showing a long term regulation of cholesterol biosynthesis activity. These results indicate that one of the anti-hyperlipidemic actions of RCE is due to inhibition of cholesterol biosynthesis in hepatic cells and provides first documentation of a hypolipidemic bio-molecular action of Rubus coreanus.
authors.affiliation: Department of Pharmacology, Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Jeonju 561–180, Republic of Korea.
authors.forename: Bidur
authors.initials: B
authors.lastname: Bhandary
authors.forename: Geum-Hwa
authors.initials: GH
authors.lastname: Lee
authors.forename: Anu
authors.initials: A
authors.lastname: Marahatta
authors.forename: Hak-Yong
authors.initials: HY
authors.lastname: Lee
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: So
authors.forename: Ji-Wung
authors.initials: JW
authors.lastname: Kwon
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Song
authors.forename: Hee-Kwon
authors.initials: HK
authors.lastname: Lee
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D000960:Hypolipidemic Agents / Q000032:analysis / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D027824:Rosaceae; D012997:Solvents / Q000737:chemistry; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; C085126:FOXO1 protein, human; D005227:Fatty Acids; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D000960:Hypolipidemic Agents; D010936:Plant Extracts; C497387:SREBF1 protein, human; D012997:Solvents; D051780:Sterol Regulatory Element Binding Protein 1; D014867:Water; D002784:Cholesterol; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005952:Glucose-6-Phosphatase