Zhang Mengyuan, Zheng Haoran, He Jiale, Zhang Mei
Department of Neurology, The First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People's Hospital), Anhui, China.
Heliyon. 2023 Oct 31;9(11):e21800. doi: 10.1016/j.heliyon.2023.e21800. eCollection 2023 Nov.
Alzheimer's disease (AD) is a progressive neurodegenerative disease that has still not been effectively treated. Paeoniflorin is a traditional Chinese medicine with potential neuroprotective effects against brain injury; however, the beneficial effects and mechanisms of action in AD have not been clarified. We aimed to explore the mechanisms of action of paeoniflorin in AD using network pharmacology and experimental validation. Network pharmacology analysis revealed 30 candidate targets through the intersection of the targets of paeoniflorin and related genes in AD, which were mainly enriched in oxidative stress and inflammation. Moreover, key targets of paeoniflorin against AD, namely Nrf2 (encoded by NFE2L2) and TLR4, were screened and found to be closely related to oxidative stress and inflammation. Subsequent experiments revealed that paeoniflorin treatment improved the cognition of APP/PS1 mice by ameliorating oxidative stress and neuroinflammation, which were associated with the upregulation of Nrf2 and HO1, and the downregulation of TLR4. Collectively, the present study demonstrates that paeoniflorin alleviates cognitive impairment in AD by regulating oxidative stress and neuroinflammation, and that Nrf2, HO1, and TLR4 could be key targets.
阿尔茨海默病（AD）是一种仍未得到有效治疗的进行性神经退行性疾病。芍药苷是一种对脑损伤具有潜在神经保护作用的传统中药；然而，其在AD中的有益作用和作用机制尚未阐明。我们旨在通过网络药理学和实验验证来探索芍药苷在AD中的作用机制。网络药理学分析通过芍药苷靶点与AD相关基因的交集揭示了30个候选靶点，这些靶点主要富集于氧化应激和炎症。此外，筛选出了芍药苷抗AD的关键靶点，即由NFE2L2编码的Nrf2和TLR4，发现它们与氧化应激和炎症密切相关。随后的实验表明，芍药苷治疗通过改善氧化应激和神经炎症来提高APP/PS1小鼠的认知能力，这与Nrf2和HO1的上调以及TLR4的下调有关。总体而言，本研究表明芍药苷通过调节氧化应激和神经炎症来减轻AD中的认知障碍，并且Nrf2、HO1和TLR4可能是关键靶点。
