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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2025-01-01
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author | Dong-Uk Kim Bitna Kweon Jinyoung Oh Yebin Lim Gyeongran Noh Jihyun Yu Hyang-Rin Kang Tackmin Kwon Kwang youll Lee Gi-Sang Bae |
author_facet | Dong-Uk Kim Bitna Kweon Jinyoung Oh Yebin Lim Gyeongran Noh Jihyun Yu Hyang-Rin Kang Tackmin Kwon Kwang youll Lee Gi-Sang Bae |
author_sort | Dong-Uk Kim |
collection | DOAJ |
description | 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. |
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institution | Kabale University |
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language | English |
publishDate | 2025-01-01 |
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spelling | doaj-art-aff39b19cbba4e73a0feb0b3555ef8c52025-01-24T13:24:01ZengMDPI AGBiomedicines2227-90592025-01-0113110310.3390/biomedicines13010103A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related NeuroinflammationDong-Uk Kim0Bitna Kweon1Jinyoung Oh2Yebin Lim3Gyeongran Noh4Jihyun Yu5Hyang-Rin Kang6Tackmin Kwon7Kwang youll Lee8Gi-Sang Bae9Department of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of KoreaDepartment of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of KoreaDepartment of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of KoreaDepartment of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of KoreaDepartment of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of KoreaDepartment of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of KoreaWoori B&B Life Science Laboratory, Jeonju 54853, Republic of KoreaWoori B&B Life Science Laboratory, Jeonju 54853, Republic of KoreaWoori B&B Life Science Laboratory, Jeonju 54853, Republic of KoreaDepartment of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of KoreaBackground/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.https://www.mdpi.com/2227-9059/13/1/103heparan sulfateneuroinflammationAlzheimer’s diseasenetwork pharmacologyBV2 |
spellingShingle | Dong-Uk Kim Bitna Kweon Jinyoung Oh Yebin Lim Gyeongran Noh Jihyun Yu Hyang-Rin Kang Tackmin Kwon Kwang youll Lee Gi-Sang Bae A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related Neuroinflammation Biomedicines heparan sulfate neuroinflammation Alzheimer’s disease network pharmacology BV2 |
title | A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related Neuroinflammation |
title_full | A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related Neuroinflammation |
title_fullStr | A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related Neuroinflammation |
title_full_unstemmed | A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related Neuroinflammation |
title_short | A Network Pharmacology Study and Experimental Validation to Identify the Potential Mechanism of Heparan Sulfate on Alzheimer’s Disease-Related Neuroinflammation |
title_sort | network pharmacology study and experimental validation to identify the potential mechanism of heparan sulfate on alzheimer s disease related neuroinflammation |
topic | heparan sulfate neuroinflammation Alzheimer’s disease network pharmacology BV2 |
url | https://www.mdpi.com/2227-9059/13/1/103 |
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