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.

背景：阿尔茨海默病（AD）是最常见的痴呆类型，发病机制复杂，尚无有效治疗方法。能量代谢紊乱作为AD的早期病理事件，作为AD研究的一个有前景的领域而受到关注。党参多糖是党参的主要有效成分，已被证明具有调节能量代谢的作用。

方法：为进一步研究党参多糖在AD中的作用和机制，本研究采用_Aβ1-40诱导的PC12细胞模型研究党参多糖的保护作用及其改善能量代谢障碍的潜在机制。

结果：结果显示，Aβ _1-40诱导 PC12 细胞活力、能量代谢分子（ATP、NAD+ 和 NAD+/NADH）和线粒体膜电位 (MMP) 的降低和 ROS 的增加。此外，还发现 Aβ _1-40增加了与 NAD+ 稳态相关的 CD38 表达，而沉默信息调节 2 同源物 1（SIRT1、SIRT3）、过氧化物酶体增殖物激活受体 γ 辅激活因子 1-α（PGC-1α）和 SIRT3 活性降低. 党参多糖增加NAD+、NAD+/NADH、SIRT3、SIRT1和与NAD+相关的PGC-1α，从而部分恢复ATP。

结论：我们的研究结果表明党参多糖保护 PC12 细胞免受 Aβ _1-40诱导的损伤，表明党参药草的这些成分可能代表 AD 患者的早期治疗选择。