5-Hydroxyferulic acid methyl ester isolated from wasabi leaves inhibits 3T3-L1 adipocyte differentiation

Phytother Res. 2018 Jul;32(7):1304-1310. doi: 10.1002/ptr.6060. Epub 2018 Feb 26.

Abstract

To investigate the compounds present in wasabi leaves (Wasabia japonica Matsumura) that inhibit the adipocyte differentiation, activity-guided fractionation was performed on these leaves. 5-Hydroxyferulic acid methyl ester (1: 5-HFA ester), one of the phenylpropanoids, was isolated from wasabi leaves as a compound that inhibits the adipocyte differentiation. Compound 1 suppressed the intracellular lipid accumulation of 3T3-L1 cells without significant cytotoxicity. Gene expression analysis revealed that 1 suppressed the mRNA expression of 2 master regulators of adipocyte differentiation, PPARγ and C/EBPα. Furthermore, 1 downregulated the expression of adipogenesis-related genes, GLUT4, LPL, SREBP-1c, ACC, and FAS. Protein expression analysis revealed that 1 suppressed PPARγ protein expression. Moreover, to investigate the relationship between the structure and activity of inhibiting the adipocyte differentiation, we synthesized 12 kinds of phenylpropanoid analog. Comparison of the activity among 1 and its analogs suggested that the compound containing the substructure that possess a common functional group at the ortho position such as a catechol group exhibits the activity of inhibiting the adipocyte differentiation. Taken together, our findings suggest that 1 from wasabi leaves inhibits adipocyte differentiation via the downregulation of PPARγ.

Keywords: 3T3-L1; 5-hydroxyferulic acid methyl ester; Wasabia japonica Matsumura; adipocyte differentiation; leaf; phenylpropanoid.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / physiology
  • Adipogenesis / drug effects*
  • Adipogenesis / genetics
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Coumaric Acids / chemistry
  • Coumaric Acids / isolation & purification*
  • Coumaric Acids / pharmacology*
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Esters / chemistry
  • Esters / isolation & purification
  • Esters / pharmacology*
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Plant Leaves / chemistry*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Wasabia / chemistry*

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Coumaric Acids
  • Esters
  • PPAR gamma
  • Sterol Regulatory Element Binding Protein 1
  • 5-hydroxyferulic acid