Background: Alzheimer's disease (AD) is the most common type of dementia and has a
complex pathogenesis with no effective treatment. Energy metabolism disorders, as an early pathological
event of AD,have attracted attention as a promising area of AD research. Codonopsis pilosula
Polysaccharides are the main effective components of Codonopsis pilosula, which have been
demonstrated to regulate energy metabolism.
Methods: In order to further study the roles and mechanisms of Codonopsis pilosula
polysaccharides in AD, this study used an Aβ1-40-induced PC12 cells model to study the protective
effects of Codonopsis pilosula polysaccharides and their potential mechanisms in improving energy
Results: The results showed that Aβ1-40 induced a decrease in PC12 cells viability, energy
metabolism molecules (ATP, NAD+, and NAD+/NADH) and Mitochondrial Membrane Potential
(MMP) and an increase in ROS. Additionally, it was found that Aβ1-40 increased CD38 expression
related to NAD+ homeostasis, whereas Silent Information Regulation 2 homolog1 (SIRT1,
SIRT3), Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and SIRT3 activity
were decreased. Codonopsis pilosula polysaccharides increased NAD+, NAD+/NADH, SIRT3,
SIRT1, and PGC-1α related to NAD+, thus partially recovering ATP.
Conclusion: Our findings reveal that Codonopsis pilosula polysaccharides protected PC12 cells
from Aβ1-40-induced damage, suggesting that these components of the Codonopsis pilosula herb
may represent an early treatment option for AD patients.