State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang 621000, China.
Molecules. 2022 Jul 12;27(14):4463. doi: 10.3390/molecules27144463.
Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that strikes millions worldwide. Herein, we demonstrate a new approach based on network target to identify anti-AD compounds from Danshen. Network pharmacology and molecular docking were employed to establish the DS-AD network, which mainly involved apoptosis of neuron cells. Then network scoring was confirmed via Connectivity Map analysis. M308 (Danshenxinkun D) was an anti-AD candidate with a high score (p < 0.01). Furthermore, we conducted ex vivo experiments with H2O2-treated PC12 cells to verify the neuroprotective effect of Salvia miltiorrhiza-containing plasma (SMP), and UPLC-Q-TOF/MS and RT-qPCR were performed to demonstrate the anti-AD activity of M308 from SMP. Results revealed that SMP could enhance cell viability and level of acetylcholine. AO/EB staining and Mitochondrial membrane potential (MMP) analysis showed that SMP significantly suppressed apoptosis, which may be due to anti-oxidative stress activity. Moreover, the effects of M308 and SMP on expressions of PSEN1, DRD2, and APP mRNA were consistent, and M308 can significantly reverse the expression of PSEN1 and DRD2 mRNA in H2O2-treated PC12 cells. The strategy based on the network could be employed to identify anti-AD compounds from Chinese herbs. Notably, M308 stands out as a promising anti-AD candidate for development.
阿尔茨海默病（AD）是一种常见的与年龄相关的神经退行性疾病，影响着全球数百万人。在此，我们展示了一种基于网络靶点的新方法，用于从丹参中筛选抗 AD 化合物。采用网络药理学和分子对接建立 DS-AD 网络，主要涉及神经元细胞凋亡。然后通过连通性映射分析对网络评分进行验证。M308（丹参心坤 D）是一种具有高评分（p < 0.01）的抗 AD 候选药物。此外，我们进行了用 H2O2 处理的 PC12 细胞的离体实验，以验证含丹参血浆（SMP）的神经保护作用，并进行 UPLC-Q-TOF/MS 和 RT-qPCR 以证明 M308 从 SMP 中具有抗 AD 活性。结果表明，SMP 可以提高细胞活力和乙酰胆碱水平。AO/EB 染色和线粒体膜电位（MMP）分析表明，SMP 显著抑制细胞凋亡，这可能是由于其抗氧化应激活性。此外，M308 和 SMP 对 PSEN1、DRD2 和 APP mRNA 表达的影响一致，M308 可显著逆转 H2O2 处理的 PC12 细胞中 PSEN1 和 DRD2 mRNA 的表达。基于网络的策略可用于从中药中筛选抗 AD 化合物。值得注意的是，M308 是一种很有前途的抗 AD 候选药物。
