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Neuroprotective Effects of Dammarane Sapogenins Against lipopolysaccharide-induced Cognitive Impairment, Neuroinflammation and Synaptic Dysfunction

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Abstract

Neuroinflammation is a critical driver in the pathogenesis and progression of neurodegenerative disorders. Dammarane sapogenins (DS), a deglycosylated product of ginsenoside, possess a variety of potent biological activities. The present study aimed to explore the neuroprotective effects of DS in a rat model of neuroinflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS). Our study revealed that DS pretreatment effectively improved LPS-induced associative learning and memory impairments in the active avoidance response test and spatial learning and memory in Morris water maze test. DS also remarkably inhibited LPS-induced neuroinflammation by suppressing microglia overactivation, pro-inflammatory cytok ine release (TNF‐α and IL‐1β) and reducing neuronal loss in the CA1 and DG regions of the hippocampus. Importantly, pretreatment with DS reversed LPS-induced upregulation of HMGB1 and TLR4 and inhibited their downstream NF-κB signaling activation, as evidenced by increased IκBα and decreased p-NF‐κB p65 levels. Furthermore, DS ameliorated LPS-induced synaptic dysfunction by decreasing MMP-9 and increasing NMDAR1 expression in the hippocampus. Taken together, this study suggests that DS could be a promising treatment for preventing cognitive impairments caused by neuroinflammation.

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Data availability

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

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Funding

This work was supported by Beijing Tongren Hospital, Capital Medical University (2020-YJJ-ZZL-050), Bethune Public Welfare Foundation (B-19-H-20200622) and Chinese Academy of Medical Sciences and Peking Union Medical College (2016-I2M-2-006).

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Authors and Affiliations

  1. Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Liming Dong, Jie Bai, Yiman Li, Zhihui Song & Chao Zhang

  2. Research Center for Pharmacology & Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China

    Liming Dong, Ning Jiang & Xinmin Liu

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  1. Liming Dong
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Contributions

Liming Dong performed the experiments and prepared the manuscript. Ning Jiang and Jie Bai provided experimental technical support. Yiman Li and Zhihui Song performed the data analysis. Xinmin Liu and Chao Zhang conceived the experiments and revised the manuscript. All authors checked and approved the final manuscript.

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Correspondence to Chao Zhang.

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This study was performed in line with the guidelines for the Animal Care and Use Committee of the Institute of Medical Plant Development, Chinese Academy of Medical Sciences, and Peking Union Medical College.

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Dong, L., Jiang, N., Bai, J. et al. Neuroprotective Effects of Dammarane Sapogenins Against lipopolysaccharide-induced Cognitive Impairment, Neuroinflammation and Synaptic Dysfunction. Neurochem Res 48, 3525–3537 (2023). https://doi.org/10.1007/s11064-023-03997-7

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