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Phenylethanoid Glycosides of Cistanche Improve Learning and Memory Disorders in APP/PS1 Mice by Regulating Glial Cell Activation and Inhibiting TLR4/NF-κB Signaling Pathway

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Abstract

Phenylethanoid Glycosides of Cistanche (PhGs) have a certain curative effect on AD animal model, Echinacea (ECH) and verbascoside (ACT), as the quality control standard of Cistanche deserticola Y. C. Ma and the main representative compounds of PhGs have been proved to have neuroprotective effects, but the specific mechanism needs to be further explored. This study explored the mechanisms of PhGs, ECH, and ACT in the treatment of Alzheimer's disease (AD) from the perspectives of glial cell activation, TLR4/NF-κB signaling pathway, and synaptic protein expression. We used APP/PS1 mice as AD models. After treatment with PhGs, ECH, and ACT, the learning and memory abilities of APP/PS1 mice were enhanced, and the pathological changes in brain tissue were alleviated. The expression of pro-inflammatory M1 microglia markers (CD11b, iNOS, and IL-1β) was decreased; the expression of M2 microglia markers (Arg-1 and TGF-β1) was increased, which promoted the transformation of microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. In addition, PhGs, ECH, and ACT could down-regulate the expression of proteins related to the TLR4/NF-κB signaling pathway and up-regulate the expression of synaptic proteins. The results indicated that PhGs, ECH, and ACT played a neuroprotective role by regulating the activation of glial cells and inhibiting the TLR4/NF-κB inflammatory pathway, and improving the expression levels of synapse-related proteins.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Department of Pharmacology, Shihezi University, Shihezi, 832000, Xinjiang, People’s Republic of China

    Chunhui Wang, Hongxia Ye, Yanjie Zheng, Yanqiang Qi, Mengyu Zhang & Yanli Hu

  2. Central Laboratory, Shenzhen Sami Medical Center, Shenzhen, China

    Yan Long

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  1. Chunhui Wang
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  2. Hongxia Ye
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  3. Yanjie Zheng
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  4. Yanqiang Qi
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  5. Mengyu Zhang
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  6. Yan Long
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  7. Yanli Hu
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Contributions

CW and YH conceived and designed research. CW conducted experiments. HY, YZ, YQ, and MZ analyzed data. CW wrote the manuscript; YH and YL revised the manuscript. YH acquired the funding and financial support for the project. All authors read and approved the manuscript for publication.

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Correspondence to Yanli Hu.

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Research Involving Animals: The animals were treated according to the guidelines of the Animal Management Rules of the Ministry of Health of the People’s Republic of China (documentation Number 55, 2001, Ministry of Health of PR China). The experiments were approved by the Committee of Experimental Animal Administration of Shihezi University.

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Wang, C., Ye, H., Zheng, Y. et al. Phenylethanoid Glycosides of Cistanche Improve Learning and Memory Disorders in APP/PS1 Mice by Regulating Glial Cell Activation and Inhibiting TLR4/NF-κB Signaling Pathway. Neuromol Med 25, 75–93 (2023). https://doi.org/10.1007/s12017-022-08717-y

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