title: Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression by thymoquinone-rich fraction and thymoquinone in HepG2 cells.
abstract: OBJECTIVE
  Nigella sativa and its active constituent thymoquinone (TQ) have been exploited for their various health benefits. This work was aimed to investigate the regulatory effects of TQ-rich fraction (TQRF) and commercial TQ on the low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) genes in HepG2 cells.
  
  
  RESULTS
  TQRF was extracted from N. sativa seeds using supercritical fluid extraction. The regulatory effects of TQRF at 80 microg/ml and TQ at 2 microg/ml on LDLR and HMGCR gene expression were investigated in HepG2 cells using quantitative real-time PCR. The TQ content in TQRF was 2.77% (w/w) and was obtained at a temperature of 40 degrees C and a pressure of 600 bar. Treatment of cells with TQRF and TQ resulted in a 7- and 2-fold upregulation of LDLR mRNA level, respectively, compared with untreated cells. The mRNA level of HMGCR was downregulated by 71 and 12%, respectively, compared with untreated cells.
  
  
  CONCLUSIONS
  TQRF and TQ regulated genes involved in cholesterol metabolism by two mechanisms, the uptake of low-density lipoprotein cholesterol via the upregulation of the LDLR gene and inhibition of cholesterol synthesis via the suppression of the HMGCR gene.
authors.affiliation: Nutraceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia.
authors.forename: Ghanya
authors.initials: G
authors.lastname: Al-Naqeep
authors.forename: Maznah
authors.initials: M
authors.lastname: Ismail
authors.forename: Zeenathul
authors.initials: Z
authors.lastname: Allaudin
mesh_terms: D016227:Benzoquinones / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000235:genetics*; D031881:Nigella sativa; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011973:Receptors, LDL / Q000187:drug effects / Q000235:genetics*
chemical_list: D016227:Benzoquinones; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011973:Receptors, LDL; D006903:Hydroxymethylglutaryl CoA Reductases; C003466:thymoquinone