Bacoside-A, an Indian Traditional-Medicine Substance, Inhibits β-Amyloid Cytotoxicity, Fibrillation, and Membrane Interactions

ACS Chem Neurosci. 2017 Apr 19;8(4):884-891. doi: 10.1021/acschemneuro.6b00438. Epub 2017 Jan 30.

Abstract

Bacoside-A, a family of compounds extracted from the Bacopa monniera plant, is a folk-medicinal substance believed to exhibit therapeutic properties, particularly enhancing cognitive functions and improving memory. We show that bacoside-A exerted significant inhibitory effects upon cytotoxicity, fibrillation, and particularly membrane interactions of amyloid-beta (1-42) (Aβ42), the peptide playing a prominent role in Alzeheimer's disease progression and toxicity. Specifically, preincubation of bacoside-A with Aβ42 significantly reduced cell toxicity and inhibited fibril formation both in buffer solution and, more significantly, in the presence of membrane vesicles. In parallel, spectroscopic and microscopic analyses reveal that bacoside-A blocked membrane interactions of Aβ42, while formation of Aβ42 oligomers was not disrupted. These interesting phenomena suggest that inhibition of Aβ42 oligomer assembly into mature fibrils, and blocking membrane interactions of the oligomers are likely the underlying factors for ameliorating amyloid toxicity by bacoside-A and its putative physiological benefits.

Keywords: amyloid−membrane interactions; bacoside-A; fibrillation inhibitors; fluorescence anisotropy; giant vesicles; β-Amyloid; β-amyloid oligomers.

MeSH terms

  • Amyloid beta-Peptides / drug effects*
  • Amyloid beta-Peptides / metabolism*
  • Cell Line
  • Cell Membrane / drug effects*
  • Humans
  • Immunoblotting
  • India
  • Medicine, Traditional / methods
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Neurons / drug effects*
  • Peptide Fragments / drug effects*
  • Peptide Fragments / metabolism*
  • Protein Aggregation, Pathological*
  • Saponins / pharmacology*
  • Triterpenes / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Saponins
  • Triterpenes
  • amyloid beta-protein (1-42)
  • bacoside A