The Additive Effects of Low Dose Intake of Ferulic Acid, Phosphatidylserine and Curcumin, Not Alone, Improve Cognitive Function in APPswe/PS1dE9 Transgenic Mice

Biol Pharm Bull. 2019;42(10):1694-1706. doi: 10.1248/bpb.b19-00332.

Abstract

Alzheimer's disease (AD) is the most common form of dementia and its prevention and treatment is a worldwide issue. Many natural components considered to be effective against AD have been identified. However, almost all clinical trials of these components for AD reported inconclusive results. We thought that multiple factors such as amyloid β (Aβ) and tau progressed the pathology of AD and that a therapeutic effect would be obtained by using multiple active ingredients with different effects. Thus, in this study, we treated ferulic acid (FA), phosphatidylserine (PS) and curcumin (Cur) in combination or alone to APPswe/PS1dE9 transgenic mice and evaluated cognitive function by Y-maze test. Consequently, only the three-ingredient group exhibited a significant improvement in cognitive function compared to the control group. In addition, we determined the amounts of Aβ, brain-derived neurotrophic factor (BDNF), interleukin (IL)-1β, acetylcholine and phosphorylated tau in the mouse brains after the treatment. In the two-ingredient (FA and PS) group, a significant decrease in IL-1β and an increasing trend in acetylcholine were observed. In the Cur group, significant decreases in Aβ and phosphorylated tau and an increasing trend in BDNF were observed. In the three-ingredient group, all of them were observed. These results indicate that the intake of multiple active ingredients with different mechanisms of action for the prevention and treatment of AD.

Keywords: Alzheimer’s disease; curcumin; ferulic acid; phosphatidylserine.

MeSH terms

  • Acetylcholine / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition / drug effects
  • Coumaric Acids / pharmacology
  • Coumaric Acids / therapeutic use*
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Drug Therapy, Combination
  • Interleukin-1beta / metabolism
  • Mice, Transgenic
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Phosphatidylserines / pharmacology
  • Phosphatidylserines / therapeutic use*
  • Presenilin-1 / genetics
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Coumaric Acids
  • Interleukin-1beta
  • Mapt protein, mouse
  • Neuroprotective Agents
  • Phosphatidylserines
  • Presenilin-1
  • tau Proteins
  • ferulic acid
  • Curcumin
  • Acetylcholine