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 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.