Paeoniflorin Atttenuates Amyloidogenesis and the Inflammatory Responses in a Transgenic Mouse Model of Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is associated with the inflammatory response in response to amyloid β-peptide (Aβ). Previous studies have suggested that paeoniflorin (PF) shows anti-inflammatory and neuroprotective effects in inflammation-related diseases. However, the impacts of PF on AD have not been investigated. In the present study, we showed that a 4-week treatment with PF could significantly inhibit Aβ burden, Aβ-induced over activation of astrocytes and microglia, downregulation of proinflammatory cytokines, and upregulation of anti-inflammatory cytokines in the brain. In addition, we demonstrated that chronic treatment with PF inhibited the activation of glycogen synthase kinase 3β (GSK-3β) and reversed neuroinflammtory-induced activation of nuclear factor-kappa B (NF-κB) signaling pathways. Moreover, PF exerted inhibitory effects on NALP3 inflammasome, caspase-1, and IL-1β. Collectively, in the present study, we demonstrated that PF exhibits neuroprotective effects in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice via inhibiting neuroinflammation mediated by the GSK-3β and NF-κB signaling pathways and nucleotide-binding domain-like receptor protein 3 inflammasome. Thus, these results suggest that PF might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.

• Authors: Hong-Ri Zhang, Jing-Hua Peng, Xiao-Bing Cheng, Bao-Zhong Shi, Mao-Ying Zhang, Ru-Xiang Xu
• Journal: Neurochemical research (Neurochem Res) Vol. 40 Issue 8 Pg. 1583-92 (Aug 2015) ISSN: 1573-6903 [Electronic] United States
• PMID: 26068144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APP protein, human
• Amyloid beta-Protein Precursor
• Glucosides
• Inflammation Mediators
• Monoterpenes
• Presenilin-1
• peoniflorin

Topics

• Alzheimer Disease (drug therapy, genetics, pathology)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Disease Models, Animal
• Glucosides (therapeutic use)
• Inflammation (drug therapy, genetics, metabolism)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Male
• Memory Disorders (drug therapy, genetics, metabolism)
• Mice
• Mice, Transgenic
• Monoterpenes (therapeutic use)
• Paeonia
• Plaque, Amyloid (drug therapy, genetics, metabolism)
• Presenilin-1 (genetics)