title: Curcumin inhibits Aβ-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways.
abstract: Amyloid β (Aβ) plays an important role in Alzheimer's disease (AD) by inducing microglia activation. Once activated, microglial cells promote the release of reactive species and cytokines that are known to enhance immune responses in AD brain. Thus, negative regulators of microglia activation are considered as potential therapeutic candidates for AD. Curcumin, the major yellow pigment in turmeric (Curcuma longa), is proposed for its anti-inflammatory properties. Several studies have indicated the suppressive effects of curcumin on LPS-induced microglia activation and MAPK activities. However, the effects of curcumin on Aβ-treated microglia and the possible mechanisms are still not fully understood. In the present study, we found that curcumin improved microglial viability against Aβ42 in a time- and dose-dependent manner and remarkably suppressed Aβ42-induced CD68 expression. Moreover, curcumin concentration-dependently abolished Aβ42-induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in mRNA and protein levels in microglia. Besides, curcumin exerted an inhibitory effect on phosphorylation of ERK1/2 and p38 in Aβ42-activated microglia. Further experiments indicated that blockage of ERK1/2 and p38 pathways reduced inflammatory cytokines production from microglia. These results show that curcumin suppresses ERK1/2 and p38 signaling, thus, attenuating inflammatory responses of brain microglia.
authors.affiliation: Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China.
authors.forename: Zhenyang
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Zengcheng People's Hospital, No. 1 Guangming East Road, Zengcheng 511300, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qi
authors.affiliation: Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China.
authors.forename: Aiwu
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China. Electronic address: wuqi8733@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China. Electronic address: fyn2012@126.com.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Fang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: Aβ; Curcumin; Inflammation; Microglia