机构：[a]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神经疾病高创中心（北京学者工作室）科技平台老年认知障碍疾病北京市重点实验室科技平台[b]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[c]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[d]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China
Dysfunction of microglia has been increasingly recognized as a causative factor in Alzheimer's disease (AD); thus, developing medicines capable of restoring microglial functions is critically important and constitutes a promising therapeutic strategy. Honokiol is a natural neuroprotective compound extracted from Magnolia officinalis, which may play roles in AD therapy.This study aimed to evaluate the role and the underlying mechanisms of honokiol in microglial phagocytosis.MTT and flow cytometry were used to assess the cell viability and apoptosis, respectively. Phagocytic capacity, mitochondrial reactive oxygen species production, and membrane potential were evaluated using fluorescence microscopy. Seahorse XF24 extracellular flux analyzer was for cell glycolysis and oxidative phosphorylation (OXPHOS) detection. Mass spectrometry was applied for metabolites measurement. Quantitative real-time polymerase chain reaction and western blotting were performed to detect the mRNA and protein level of PPARγ and PGC1α, respectively.Honokiol alleviated Aβ 42-induced BV2 neurotoxicity. Honokiol promoted phagocytic efficiency of BV2 cells through reversing a metabolic switch from OXPHOS to anaerobic glycolysis and enhancing ATP production. Meanwhile, honokiol reduced mitochondrial reactive oxygen species (ROS) production and elevated mitochondrial membrane potential. Moreover, honokiol increased the expression of PPARγ and PGC1α, which might play positive roles in energy metabolism and microglial phagocytosis.In this study, honokiol was identified as an effect natural product capable of enhancing mitochondrial function thus promoting microglial phagocytic function.
基金：
This study was supported by the Key Project of
the National Natural Science Foundation of China
(81530036); the National Key Scientific Instrument
and Equipment Development Project (31627803);
the Key Project of the National Natural Science
Foundation of China (U20A20354); Beijing Scholars Program; Beijing Brain Initiative from Beijing Municipal Science & Technology Commission (Z201100005520016, Z201100005520017); the
National Natural Science Foundation of China
(81801048).
第一作者机构：[a]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：[a]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China[b]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China[c]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[d]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China[*1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
推荐引用方式(GB/T 7714)：
Wenwen Li,Shiyuan Wang,Heng zhang,et al.Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming.[J].JOURNAL OF ALZHEIMERS DISEASE.2021,82(4):1475-1485.doi:10.3233/JAD-210177.
APA：
Wenwen Li,Shiyuan Wang,Heng zhang,Bingqiu Li,Lingzhi Xu...&Jianping Jia.(2021).Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming..JOURNAL OF ALZHEIMERS DISEASE,82,(4)
MLA：
Wenwen Li,et al."Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming.".JOURNAL OF ALZHEIMERS DISEASE 82..4(2021):1475-1485
