Codonopsis pilosula Polysaccharides Alleviate Aβ _1-40-Induced PC12 Cells Energy Dysmetabolism via CD38/NAD+ Signaling Pathway

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 Aβ_1-40-induced PC12 cells model to study the protective effects of Codonopsis pilosula polysaccharides and their potential mechanisms in improving energy metabolism dysfunction.

Results: The results showed that Aβ_1-40 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 Aβ_1-40 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 Aβ_1-40-induced damage, suggesting that these components of the Codonopsis pilosula herb may represent an early treatment option for AD patients.