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...

Full description

Saved in:
Bibliographic Details
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
Subjects:
Online Access:https://www.mdpi.com/2227-9059/13/1/103
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832589000953561088
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.
format Article
id doaj-art-aff39b19cbba4e73a0feb0b3555ef8c5
institution Kabale University
issn 2227-9059
language English
publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Biomedicines
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
work_keys_str_mv AT dongukkim anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT bitnakweon anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT jinyoungoh anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT yebinlim anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT gyeongrannoh anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT jihyunyu anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT hyangrinkang anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT tackminkwon anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT kwangyoulllee anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT gisangbae anetworkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT dongukkim networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT bitnakweon networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT jinyoungoh networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT yebinlim networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT gyeongrannoh networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT jihyunyu networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT hyangrinkang networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT tackminkwon networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT kwangyoulllee networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation
AT gisangbae networkpharmacologystudyandexperimentalvalidationtoidentifythepotentialmechanismofheparansulfateonalzheimersdiseaserelatedneuroinflammation