Wedelolactone inhibits adipogenesis through the ERK pathway in human adipose tissue-derived mesenchymal stem cells

J Cell Biochem. 2012 Nov;113(11):3436-45. doi: 10.1002/jcb.24220.

Abstract

Wedelolactone is an herbal medicine that is used to treat septic shock, hepatitis and venom poisoning. Although in differentiated and cancer cells, wedelolactone has been identified as anti-inflammatory, growth inhibitory, and pro-apoptotic, the effects of wedelolactone on stem cell differentiation remain largely unknown. Here, we report that wedelolactone inhibits the adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Wedelolactone reduced the formation of lipid droplets and the expression of adipogenesis-related proteins, such as CCAAT enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein aP2 (aP2). Wedelolactone mediated this process by sustaining ERK activity. In addition, inhibition of ERK activity with PD98059 resulted in reversion of the wedelolactone-mediated inhibition of adipogenic differentiation. Taken together, these results indicate that wedelolactone inhibits adipogenic differentiation through ERK pathway and suggest a novel inhibitory effect of wedelolactone on adipogenic differentiation in hAMSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adult
  • Anti-Obesity Agents / pharmacology*
  • CCAAT-Enhancer-Binding Protein-alpha / antagonists & inhibitors
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • Cell Differentiation
  • Coumarins / pharmacology*
  • Fatty Acid-Binding Proteins / antagonists & inhibitors
  • Fatty Acid-Binding Proteins / genetics
  • Female
  • Flavonoids / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Lipoprotein Lipase / antagonists & inhibitors
  • Lipoprotein Lipase / genetics
  • MAP Kinase Signaling System / drug effects*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics
  • Primary Cell Culture
  • Subcutaneous Fat / cytology
  • Subcutaneous Fat / drug effects*
  • Subcutaneous Fat / metabolism

Substances

  • Anti-Obesity Agents
  • CCAAT-Enhancer-Binding Protein-alpha
  • Coumarins
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • Flavonoids
  • PPAR gamma
  • wedelolactone
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Lipoprotein Lipase
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one