Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice
2016
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by
aggregation of amyloid-β (Aβ) peptide in the hippocampus and cortex of brain. Neuroinflammation is
considered a driving force of the progression of cognitive decline in AD. During the neuroinflammatory
process, activated astrocytes and microglia induced by Aβ peptide produce pro-inflammatory factors
and neurotoxins, which promote neurodegeneration in AD brain, eventually dementia. Thus, the
suppression of glial over-activation in AD brain might result in therapeutic effect. Triptolide, a natural compound extracted
from the Chinese medicinal herb Tripterygium wilfordii Hook F., has shown anti-inflammatory effects. Whether
triptolide exhibits preventive effects on AD-like pathology via anti-inflammatory action is unclear. The present study
showed that intraperitoneal injection of triptolide (20 μg/kg) for 15 weeks markedly alleviated deficits in learning and
memory, and prevented Aβ accumulation in the brain of AD transgenic mice (APP/PS1 mice). These results were accompanied
by reduction in glial activation and contents of pro-inflammatory factors in the brain of APP/PS1 mice treated by
triptolide compared to saline-treated APP/PS1 mice. In addition, we observed that the Mitogen-activated protein kinases
(MAPKs, including p38, ERK and JNK) phosphorylation was also suppressed by treatment of triptolide in the brain of
APP/PS1 mice. Taken together, our study suggests that molecular mechanisms underlying the therapeutic effects of triptolide
on the AD model might involve inhibition of the neuroinflammation by suppressing MAPKs activity.
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