title: Aralia cordata inhibits triacylglycerol biosynthesis in HepG2 cells.
abstract: Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first committed step in triacylglycerol (TAG) and phospholipid biosynthesis, and has been considered as one of the drug targets for treating hepatic steatosis, insulin resistance, and other metabolic disorders. The aim of this study was to investigate the GPAT inhibitors from natural products and to evaluate their effects. The methanol extract of Aralia cordata roots showed a strong inhibitory effect on the human GPAT1 activity. A further bioactivity-guided approach led to the isolation of ent-pimara-8(14),15-dien-19-oic acid, (PA), one of the major compounds of A. cordata, which suppressed the GPAT1 activity with IC50 value of 60.5 μM. PA markedly reduced de novo lysophosphatidic acid synthesis through inhibition of GPAT activity and therefore significantly decreased synthesis of TAG in the HepG2 cells. These results suggest that PA as well as A. cordata root extract could be beneficial in controlling lipid metabolism.
authors.affiliation: 1 Targeted Medicine Research Center , Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongwon-Gun, Korea.
authors.forename: Mun Ock
authors.initials: MO
authors.lastname: Kim
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Jee Hee
authors.initials: JH
authors.lastname: Seo
authors.forename: Il Soon
authors.initials: IS
authors.lastname: Kim
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Han
authors.forename: Dong Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
authors.forename: Long
authors.initials: L
authors.lastname: Cui
authors.forename: Jungwoo
authors.initials: J
authors.lastname: Kim
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Lee
mesh_terms: D027983:Aralia / Q000737:chemistry*; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D010936:Plant Extracts; D014280:Triglycerides; C008911:pimaric acid; D005992:Glycerol-3-Phosphate O-Acyltransferase; C032881:lysophosphatidic acid