title: Phaleria macrocarpa (Scheff.) Boerl fruit aqueous extract enhances LDL receptor and PCSK9 expression in vivo and in vitro.
abstract: BACKGROUND
  Phaleria macrocarpa (Scheff.) Boerl (Pm) has been shown to reduce cholesterol level in vitro and in vivo experiment.
  
  
  OBJECTIVE
  This study investigated the effects of Pm fruit on weight control and mechanistic basis of its anti-hypercholesterolemic effect in both in vivo and in vitro.
  
  
  METHODS
  In the in vivo study, thirty six male Sprague Dawley were randomized to six groups. Five groups were induced into hypercholesterolemia by giving 3% cholesterol enriched-diet for 52 days while one group acted as control. The rats were then treated with Pm extract (0, 20, 30 and 40 mg/ml) or simvastatin for 84 days. The following parameters were determined: (1) body weight, (2) blood lipid profile (total cholesterol, triglyceride, HDL and LDL) and (3) hepatic LDL receptor (160 kDa and 120 kDa) and PCSK9 proteins. In the in vitro study, HepG2 cells were cultured in serum-free RPMI supplemented with 0.2% BSA with or without LDL and in the presence of Pm extract (0, 0.1, 2, 40 and 1,000 μg/ml) or simvastatin (4.60 μg/ml) for 24h. The abundance of both LDL receptor and PCSK9 proteins and mRNA were investigated.
  
  
  RESULTS
  Pm extract significantly (P<0.05) reduced body weight gain, total cholesterol, triglycerides, HDL LDL levels and upregulated hepatic LDL receptor as well as PCSK9 proteins of hypercholesterolemic rats. These results were supported by studies in HepG2 cells whereby Pm extract also significantly upregulated both LDL receptor and PCSK9 at protein and mRNA levels.
  
  
  CONCLUSIONS
  This study enhances the potential usage of Pm fruit for controlling the body weight of obese people and for treating hypercholesterolemia.
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
authors.forename: Soo Ching
authors.initials: SC
authors.lastname: Chong
authors.forename: Mohamad Aziz
authors.initials: MA
authors.lastname: Dollah
authors.forename: Pei Pei
authors.initials: PP
authors.lastname: Chong
authors.forename: Abdullah
authors.initials: A
authors.lastname: Maha
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D056945:Hep G2 Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry; D029645:Thymelaeaceae / Q000737:chemistry; D013997:Time Factors; D015854:Up-Regulation; D014867:Water / Q000737:chemistry; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D010936:Plant Extracts; D012333:RNA, Messenger; D011973:Receptors, LDL; D012997:Solvents; D014867:Water; D019821:Simvastatin; C472125:PCSK9 protein, human; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases