机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China神经科系统神经内科首都医科大学宣武医院[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China
Aims: We aimed to explore the role and molecular mechanism of polygalacic acid (PA) extracted from traditional Chinese medicine Polygala tenuifolia in the treatment of Alzheimer's disease (AD). Methods: The network pharmacology analysis was used to predict the potential targets and pathways of PA. Molecular docking was applied to analyze the combination between PA and core targets. A beta 42 oligomer-induced AD mice model and microglia were used to detect the effect of PA on the release of pro-inflammatory mediators and its further mechanism. In addition, a co-culture system of microglia and neuronal cells was constructed to assess the effect of PA on activating microglia-mediated neuronal apoptosis. Results: We predict that PA might regulate inflammation by targeting PPAR gamma-mediated pathways by using network pharmacology. In vivo study, PA could attenuate cognitive deficits and inhibit the expression levels of inflammation-related factors. In vitro study, PA can also decrease the production of activated microglia-mediated inflammatory cytokines and reduce the apoptosis of N2a neuronal cells. PPAR gamma inhibitor GW9662 inversed the neuroprotective effect of PA. Both in vivo and in vitro studies showed PA might attenuate the inflammation through the PPAR gamma/NF-kappa B pathway. Conclusions: PA is expected to provide a valuable candidate for new drug development for AD in the future.
基金：
National Key Scientific Instrument and
Equipment Development Projects of
China, Grant/Award Number: 31627803;
Beijing Scholars Program; Beijing Brain
Initiative from Beijing Municipal Science
and Technology Commission, Grant/
Award Number: Z201100005520017 and
Z201100005520016; Key Project of the
National Natural Science Foundation of
China, Grant/Award Number: 81530036
and U20A20354
第一作者机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
通讯作者：
通讯机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China
推荐引用方式(GB/T 7714)：
Zhao Tan,Jia Jianping.Polygalacic acid attenuates cognitive impairment by regulating inflammation through PPARγ/NF-κB signaling pathway[J].CNS NEUROSCIENCE & THERAPEUTICS.2024,30(2):e14581.doi:10.1111/cns.14581.
APA：
Zhao, Tan&Jia, Jianping.(2024).Polygalacic acid attenuates cognitive impairment by regulating inflammation through PPARγ/NF-κB signaling pathway.CNS NEUROSCIENCE & THERAPEUTICS,30,(2)
MLA：
Zhao, Tan,et al."Polygalacic acid attenuates cognitive impairment by regulating inflammation through PPARγ/NF-κB signaling pathway".CNS NEUROSCIENCE & THERAPEUTICS 30..2(2024):e14581
