A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related Neuroinflammation

Background/Objectives: Heparan sulfate (HS) is a polysaccharide that is found on the surface of cells and has various biological functions in the body. Methods: The purpose of this study was to predict the pharmacological effects and molecular mechanisms of HS on Alzheimer’s disease (AD) and neuroin...

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Main Authors: Dong-Uk Kim, Bitna Kweon, Jinyoung Oh, Yebin Lim, Gyeongran Noh, Jihyun Yu, Hyang-Rin Kang, Tackmin Kwon, Kwang youll Lee, Gi-Sang Bae
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/103
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Summary:Background/Objectives: Heparan sulfate (HS) is a polysaccharide that is found on the surface of cells and has various biological functions in the body. Methods: The purpose of this study was to predict the pharmacological effects and molecular mechanisms of HS on Alzheimer’s disease (AD) and neuroinflammation (NI) through a network pharmacology analysis and to experimentally verify them. Results: We performed functional enrichment analysis of common genes between HS target genes and AD-NI gene sets and obtained items such as the “Cytokine-Mediated Signaling Pathway”, “Positive Regulation Of MAPK Cascade”, and “MAPK signaling pathway”. To confirm the predicted results, the anti-inflammatory effect of HS was investigated using lipopolysaccharide (LPS)-stimulated BV2 microglia cells. HS inhibited the production of nittic oxide, interleukin (IL)-6, and tumor necrosis factor-α in LPS-stimulated BV2 cells, but not IL-1β. In addition, HS inactivated P38 in the MAPK signaling pathway. Conclusions: These findings suggest the potential for HS to become a new treatment for AD and NI.
ISSN:2227-9059