Isobavachalcone and bavachinin from Psoraleae Fructus modulate Aβ42 aggregation process through different mechanisms in vitro

FEBS Lett. 2013 Sep 17;587(18):2930-5. doi: 10.1016/j.febslet.2013.07.037. Epub 2013 Jul 29.

Abstract

Spontaneous aggregation of Aβ is a key factor in the development of Alzheimer's disease. In searching for Aβ aggregation inhibitors from traditional Chinese herbal medicines, we identified two active compounds from Psoraleae Fructus, namely isobavachalcone and bavachinin. We further demonstrated that the two compounds modulate Aβ42 aggregation process through different mechanisms. Isobavachalcone significantly inhibits both oligomerization and fibrillization of Aβ42, whereas bavachinin inhibits fibrillization and leads to off-pathway aggregation. Both of the compounds attenuated Aβ42-induced toxicity in a SH-SY5Y cell model. These findings may provide valuable information for new drug development and Alzheimer's therapy in the future.

Keywords: AD; Aggregation inhibitor; Alzheimer’s disease; Amyloid beta; Aβ; BC; BCN; BKC; Bavachinin; IBC; IPL; Isobavachalcone; NBIF; PFE; PL; PLD; Psoraleae Fructus; ThT; amyloid-beta peptide; bakuchiol; bavachin; bavachinin; isobavachalcone; isopsoralen; methanol extract of Psoraleae Fructus; neobavaisoflavone; psoralen; psoralidin; thioflavin T.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / chemical synthesis
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Chalcones / chemistry*
  • Chalcones / isolation & purification
  • Chalcones / pharmacology
  • Drugs, Chinese Herbal / chemistry*
  • Flavonoids / chemistry*
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology
  • Fruit / chemistry*
  • Humans
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacology
  • Protein Multimerization / drug effects
  • Psoralea / chemistry*

Substances

  • Amyloid beta-Peptides
  • Chalcones
  • Drugs, Chinese Herbal
  • Flavonoids
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • bavachinin
  • isobavachalcone