title: 4-Hydroxyderricin and xanthoangelol from Ashitaba (Angelica keiskei) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways.
abstract: METHODS
  Adipocytes differentiation is deeply involved in the onset of obesity. 4-Hydroxyderricin (4HD) and xanthoangelol (XAG) are the chalcones that are derived from Ashitaba (Angelica keiskei). In this study, we demonstrated the inhibitory effects of these chalcones on adipocytes differentiation.
  
  
  RESULTS
  4HD and XAG suppressed intracellular lipid accumulation by Oil red O staining at 5 μM without cytotoxicity. They inhibited adipocytes differentiation accompanied by down-expression of adipocyte-specific transcription factors, CCAAT/enhancer-binding protein-β (C/EBP-β), C/EBP-α, and peroxisome proliferator-activated receptor gamma (PPAR-γ) using RT-PCR and Western blotting analysis. To obtain insights into the underlying mechanism, the activation of AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase pathways was investigated. These two chalcones promoted phosphorylation of AMPK and acetyl CoA carboxylase during differentiation of 3T3-L1 adipocytes accompanied by a decrease in glycerol-3-phosphate acyl transferase-1 and an increase in carnitine palmitoyltransferase-1 mRNA expression. These chalcones also promoted phosphorylation of extracellular signal-regulated kinases and Jun aminoterminal kinases, but not p38. Moreover, the inhibitors for AMPK and extracellular signal-regulated kinases abolished the chalcones-caused down-expression of C/EBP-β, C/EBP-α, and PPAR-γ. Treatment with Jun aminoterminal kinases inhibitor abolished the down-expression of C/EBP-α and PPAR-γ, but not C/EBP-β.
  
  
  CONCLUSIONS
  4HD and XAG inhibit adipocytes differentiation through AMPK and mitogen-activated protein kinase pathways, resulting in the down-expression of adipocyte-specific transcription factors.
authors.affiliation: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe, Japan.
authors.forename: Tianshun
authors.initials: T
authors.lastname: Zhang
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sawada
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C545013:Cebpb protein, mouse; D047495:PPAR gamma; D010936:Plant Extracts; D014157:Transcription Factors; C068243:4-hydroxyderricin; D002599:Chalcone; C068244:xanthoangelol; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Ashitaba chalcones; CCAAT/enhancer-binding proteins; Mitogen-activated protein kinases; Peroxisome proliferator-activated receptor gamma