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Tripchlorolide protects neuronal cells from microglia‐mediated β‐amyloid neurotoxicity through inhibiting NF‐κB and JNK signaling
Author(s) -
Pan XiaoDong,
Chen XiaoChun,
Zhu YuanGui,
Chen LiMin,
Zhang Jing,
Huang TianWen,
Ye QinYong,
Huang HuaPin
Publication year - 2009
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20844
Subject(s) - microglia , neuroinflammation , neurotoxicity , p38 mitogen activated protein kinases , biology , nitric oxide , microbiology and biotechnology , nf κb , phosphorylation , nitric oxide synthase , mapk/erk pathway , tumor necrosis factor alpha , signal transduction , inflammation , pharmacology , immunology , endocrinology , medicine , toxicity
Recent research has focused on soluble oligomeric assemblies of β‐amyloid peptides (Aβ) as the proximate cause of neuroinflammation, synaptic loss, and the eventual dementia associated with Alzheimer's disease (AD). In this study, tripchlorolide (T 4 ), an extract of Tripterygium wilfordii Hook. F (TWHF), was studied as a novel agent to suppress neuroinflammatory process in microglial cells and to protect neuronal cells against microglia‐mediated oligomeric Aβ toxicity. T 4 significantly attenuated oligomeric Aβ(1‐42)‐induced release of inflammatory productions such as tumor necrosis factor‐α, interleukin‐1β, nitric oxide (NO), and prostaglandin E 2 . It also downregulated the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in microglial cells. Further molecular mechanism study demonstrated that T 4 inhibited the nuclear translocation of nuclear factor‐κB (NF‐κB) without affecting I‐κBα phosphorylation. It repressed Aβ‐induced JNK phosphorylation but not ERK or p38 MAPK. The inhibition of NF‐κB and JNK by T 4 is correlated with the suppression of inflammatory mediators in Aβ‐stimulated microglial cells. These results suggest that T 4 protects neuronal cells by blocking inflammatory responses of microglial cells to oligomeric Aβ(1‐42) and that T 4 acts on the signaling of NF‐κB and JNK, which are involved in the modulation of inflammatory response. Therefore, T 4 may be an effective agent in modulating neuroinflammatory process in AD. © 2009 Wiley‐Liss, Inc.