title: Palmiwon attenuates hepatic lipid accumulation and hyperlipidemia in a menopausal rat model.
abstract: OBJECTIVE
  We examined the phytoestrogenic effects of palmiwon on breast carcinoma, lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells, and lipid-related diseases in a rat model of menopausal hyperlipidemia.
  
  
  METHODS
  E-Screen assay was used to screen for phytoestrogens, especially those with antiestrogenic activity, in MCF-7 cells. Oil Red O staining and intracellular cholesterol analyses were used to quantify cellular cholesterol levels. 3-Hydroxy-3-methyl glutaryl coenzyme A reductase assay was used to measure enzyme activity. The levels of phosphorylated adenosine monophosphate-activated protein kinases and products of genes involved in cholesterol synthesis were measured by Western blot analysis. Thirty rats were either ovariectomized or sham-operated and randomly assigned to four groups (n = 5)-Sham, OVX, OVX-SV, or OVX-PMW (50, 150, or 450 mg/kg) group-for 8 weeks. A number of targets associated with lipid-related diseases were examined to confirm the estrogenic effects of palmiwon.
  
  
  RESULTS
  Palmiwon showed antiestrogenic activity in MCF-7 cells. Palmiwon decreased lipid accumulation, total cholesterol levels, and low-density lipoprotein/very-low-density lipoprotein levels in HepG2 cells. Moreover, palmiwon reversed the effects of methyl-β-cyclodextrin on cholesterol synthesis regulators and inhibited the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase. Phosphorylation of adenosine monophosphate-activated protein kinase was stimulated by palmiwon. In ovariectomized rats, palmiwon reduced retroperitoneal and perirenal fat accumulation, serum lipids, atherogenic index, cardiac risk factor score, intima-media thickness, and nonalcoholic steatohepatitis scores.
  
  
  CONCLUSIONS
  These results indicate that palmiwon inhibits lipid accumulation without estrogenic activity in the breast. Therefore, palmiwon may have potential as a therapeutic agent for the treatment of hyperlipidemia in postmenopausal women.
authors.affiliation: From the KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Go
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Ryuk
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Byoung Seob
authors.initials: BS
authors.lastname: Ko
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D056945:Hep G2 Cells / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000209:etiology; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D061986:MCF-7 Cells / Q000378:metabolism; D008593:Menopause; D023421:Models, Animal; D010766:Phosphorylation / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins
chemical_list: D004365:Drugs, Chinese Herbal; D004967:Estrogens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008077:Lipoproteins, LDL; D048789:Phytoestrogens; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C000606987:palmiwon; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D017868:Cyclic AMP-Dependent Protein Kinases