Dual Role of Phenyl Amides from Hempseed on BACE 1, PPARγ, and PGC-1α in N2a-APP Cells

J Nat Prod. 2021 Sep 24;84(9):2447-2453. doi: 10.1021/acs.jnatprod.1c00435. Epub 2021 Aug 30.

Abstract

In Alzheimer's disease (AD) the accumulation of amyloid β (Aβ) plaques in the brain leads to neuroinflammation, neuronal cell dysfunction, and progressive memory loss. Therefore, blocking the formation of Aβ plaques has emerged as one of the most promising strategies to develop AD treatments. Hempseed is widely used as a food, and recently its compounds have shown beneficial effects on neuroinflammation. The objective of this study was to investigate whether a fraction rich in phenyl amide compounds, N-trans-caffeoyltyramine (CAFT) and N-trans-coumaroyltyramine (CUMT), can affect gene expression: β-site amyloid-precursor-protein-cleaving enzyme 1 (BACE 1), peroxisome proliferator-activated receptor gamma (PPAR γ), and PPARγ-coactivator-1α (PGC-1α) in N2a-APP cells. The mRNA levels were measured using RT-qPCR. The ethyl acetate fraction and CAFT were found to reduce BACE1 gene expression and are promissory PPARγ and PGC-1α natural agonists. The results show that hempseed compounds can inhibit the expression of BACE 1, which is involved in the accumulation of Aβ plaques and positively affect transcription factors involved in complex and diverse biological functions.

MeSH terms

  • Alzheimer Disease
  • Amides / pharmacology*
  • Amyloid Precursor Protein Secretases*
  • Amyloid beta-Peptides
  • Animals
  • Aspartic Acid Endopeptidases*
  • Cannabis / chemistry*
  • Cell Line
  • Gene Expression / drug effects
  • Mice
  • Molecular Structure
  • PPAR gamma*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha*
  • Phytochemicals / pharmacology
  • Seeds / chemistry
  • Spain
  • Tyramine / pharmacology

Substances

  • Amides
  • Amyloid beta-Peptides
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Phytochemicals
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse
  • Tyramine