Dracunculin Inhibits Adipogenesis in Human Bone Marrow-Derived Mesenchymal Stromal Cells by Activating AMPK and Wnt/β-Catenin Signaling

Int J Mol Sci. 2022 Jan 7;23(2):653. doi: 10.3390/ijms23020653.

Abstract

Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/β-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/β-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of β-catenin compared with diminished nuclear PPARγ levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the β-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.

Keywords: AMPK; Wnt/β-catenin; adipogenesis; dracunculin; hBM-MSC.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adipogenesis / drug effects*
  • Artemisia / chemistry*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Molecular Structure
  • PPAR gamma / genetics
  • Phosphorylation / drug effects
  • Wnt Signaling Pathway / drug effects*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Coumarins
  • PPAR gamma
  • PPARG protein, human
  • AMP-Activated Protein Kinases