1. Curcumin inhibits Aβ-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways.
- Author
-
Shi X, Zheng Z, Li J, Xiao Z, Qi W, Zhang A, Wu Q, and Fang Y
- Subjects
- Amyloid beta-Peptides metabolism, Animals, Animals, Newborn, Cells, Cultured, Interleukin-1beta biosynthesis, Interleukin-1beta genetics, Interleukin-6 biosynthesis, Interleukin-6 genetics, MAP Kinase Signaling System, Mice, Inbred BALB C, Microglia immunology, Microglia metabolism, Peptide Fragments metabolism, Phosphorylation, RNA, Messenger metabolism, Tumor Necrosis Factor-alpha biosynthesis, Tumor Necrosis Factor-alpha genetics, Amyloid beta-Peptides toxicity, Anti-Inflammatory Agents pharmacology, Curcumin pharmacology, Microglia drug effects, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Peptide Fragments toxicity, p38 Mitogen-Activated Protein Kinases metabolism
- 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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF