title: Anti-adipogenic activity of 2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone from Rubia cordifolia L.
abstract: To examine anti-adipogenic activity of 2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone (CMEP-NQ) isolated from the roots of Rubia cordifolia L., its effects on cell viability, apoptosis, and adipogenesis in 3T3-L1 preadipocytes were investigated. The inhibitory effect of CMEP-NQ on cell viability was more significant in differentiated mature adipocytes than in 3T3-L1 preadipocytes. In 3T3-L1 cells, the cytotoxicity of CMEP-NQ (20-40 μM) was accompanied by apoptotic events such as mitochondrial membrane potential loss, caspase-3 activation, poly(ADP-ribose) polymerase degradation, and terminal deoxynucleotidyl transferase-meidated dUTP nick-end labeling-positive apoptotic DNA fragmentation. Although the presence of 10 μM CMEP-NQ during induced adipocytic differentiation of 3T3-L1 cells for 6 days failed to influence the cell viability, it did reduce the differentiation-associated accumulation of intracellular lipid by approximately 48.5%. A similar level of inhibition was observed when 10 μM CMEP-NQ was present during the early stage (Days 0-2) of the differentiation period. At the same time, the expressions of CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor γ1, peroxisome proliferator-activated receptor γ2, and adiponectin were down-regulated. However, the presence of 10 μM CMEP-NQ during either the middle (Days 2-4) or late (Days 4-6) stage of the differentiation period caused the inhibition to a lesser extent. These results indicated that CMEP-NQ at high concentrations (20-40 μM) exerted cytotoxicity via inducing apoptosis, whereas CMEP-NQ at a low concentration (10 μM) suppressed adipocytic differentiation without exerting cytotoxicity in 3T3-L1 preadipocytes.
authors: Laboratory of Immunobiology, School of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors: Do Youn
authors: DY
authors: Jun
authors: Cho Rong
authors: CR
authors: Han
authors: Ji Young
authors: JY
authors: Lee
authors: Wan
authors: W
authors: Park
authors: Myung Sook
authors: MS
authors: Choi
authors: Mi Hee
authors: MH
authors: Woo
authors: Young Ho
authors: YH
authors: Kim
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D015536:Down-Regulation; D051379:Mice; D051336:Mitochondrial Membranes / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D045470:Rubia / Q000737:chemistry*
chemical_list: C560543:2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone; D052242:Adiponectin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D009285:Naphthoquinones; D047495:PPAR gamma; D010936:Plant Extracts; D011065:Poly(ADP-ribose) Polymerases; D004253:DNA Nucleotidylexotransferase; C505409:Casp3 protein, mouse; D053148:Caspase 3