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

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.

Phosphatidylserine, inflammation, and central nervous system diseases

“…Thirdly, PS reduces the production of Aβ in CHO-APP/PS1 cells and Aβ-induced toxicity to primary hippocampal neurons ( Xu et al, 2021 ). In addition, PS could combine with others drugs or function as a drug carrier to improve AD symptoms, for example, PS combines with ferulic acid and curcumin significantly to inhibit Aβ production, phosphorylated tau, and IL1β release, and increase brain-derived neurotrophic factor and acetylcholine ( Okuda et al, 2019 ). PS also serves as drug delivery approach for metformin and nicotinamide to ameliorate the cognitive function and inflammation ( Vakilinezhad et al, 2018 ; Saffari et al, 2020 ).…”

Action Mechanisms of Curcumin in Alzheimer’s Disease and Its Brain Targeted Delivery

“…Both soluble and insoluble Aβ plaques decreased with co-administration of the antioxidants. Moreover, the pro-inflammatory marker IL-1β decreased further [ 142 ].…”

Regulation of Membrane Phospholipid Homeostasis in Neurodegenerative Diseases

“…PL containing ether bonds particularly in PE (PE-plasmalogens) are deficient in PD patients and can be rescued by oral supplementation of PE plasmalogens [181]. PS combined with ferulic acid and curcumin significantly improved cognitive function in an AD-like mouse model with a reduced Aβ load, reduced neuroinflammation and an increased acetylcholine level [182]. Lastly, PL lipid vesicle for drug-delivery across the blood-brain barrier (BBB) are also a form of lipid molecule for increased n-3 PUFA brain availability [183].…”