<br>网络药理学和体内研究揭示了芍药苷对阿尔茨海默病的神经保护作用,Heliyon

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网络药理学和体内研究揭示了芍药苷对阿尔茨海默病的神经保护作用
Heliyon ( IF 3.4 ) Pub Date : 2023-10-31 , DOI: 10.1016/j.heliyon.2023.e21800
Mengyuan Zhang ₁ , Haoran Zheng ₁ , Jiale He ₁ , Mei Zhang ₁

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阿尔茨海默病（AD）是一种进行性神经退行性疾病，至今仍未得到有效治疗。芍药苷是一种中药，对脑损伤具有潜在的神经保护作用;然而，AD 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，筛选了芍药苷抗 AD 的关键靶点，即 Nrf2 （由 NFE2L2 编码）和 TLR4，发现与氧化应激和炎症密切相关。随后的体内实验表明，芍药苷处理通过改善氧化应激和神经炎症来改善 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。总的来说，本研究表明，芍药苷通过调节氧化应激和神经炎症来缓解 AD 患者的认知障碍，并且 Nrf2 、 HO1 和 TLR4 可能是关键靶点。

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Network pharmacology and in vivo studies reveal the neuroprotective effects of paeoniflorin on Alzheimer's disease

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 in vivo 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.

更新日期：2023-10-31

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