Protective effect of Nelumbo nucifera extracts on beta amyloid protein induced apoptosis in PC12 cells, in vitro model of Alzheimer's disease

J Food Drug Anal. 2018 Jan;26(1):172-181. doi: 10.1016/j.jfda.2017.01.007. Epub 2017 Mar 17.

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. β-Amyloid (Aβ) has been proposed to play a role in the pathogenesis of AD. Deposits of insoluble Aβ are found in the brains of patients with AD and are one of the pathological hallmarks of the disease, but the underlying signaling pathways are poorly understood. In order to develop antidementia agents with potential therapeutic value, we examined the inhibitory effect of the Nelumbo nucifera seed embryo extracts on to the aggregated amyloid β peptide (agg Aβ1-40)-induced damage of differentiated PC-12 cells (dPC-12), a well-known cell model for AD. In the present study, seed embryos of N. nucifera were extracted with 70% methanol in water and then separated into hexane, ethyl acetate, n-butanol, and water layers. Among them, only the n-butanol layer showed strong activity and was therefore subjected to separation on Sephadex LH-20 chromatography. Two fractions showing potent activity were found to significantly inhibit Aβ1-40 toxicity on dPC-12 cells in increasing order of concentration (10-50 μg/mL). Further purification and characterization of these active fractions identified them to be flavonoids such as rutin, orientin, isoorientin, isoquercetrin, and hyperoside. 2,2-Diphenyl-1-picrylhydrazyl hydrate scavenging activity of the extracts was also carried out to ascertain the possible mechanism of the activity.

Keywords: Alzheimer's disease; Nelumbo nucifera; antioxidant effect; flavonoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Chromatography, High Pressure Liquid
  • Molecular Structure
  • Nelumbo / chemistry*
  • PC12 Cells
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Protein Aggregates / drug effects
  • Protein Aggregation, Pathological
  • Rats
  • Reactive Oxygen Species

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Plant Extracts
  • Protein Aggregates
  • Reactive Oxygen Species

Grants and funding

This study was supported by grant DOH93-TD-113-025 from the Department of Health, Executive Yuan, Taiwan.