title: Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice.
abstract: 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.
authors.forename: Yan-Qiu
authors.initials: YQ
authors.lastname: Cui
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
authors.forename: Jun-Ya
authors.initials: JY
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Capital Medical University, 10 Xitoutiao, Youanmen, Beijing 100069, PR China. xmwang@ccmu.edu.cn.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D053764:Presenilin-1 / Q000235:genetics; D066263:Protein Aggregation, Pathological / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; C508853:PSEN1 protein, human; D010616:Phenanthrenes; D053764:Presenilin-1; C001899:triptolide; D020928:Mitogen-Activated Protein Kinases