Abstract
BackgroundAlzheimer’s disease (AD) is a type of progressive neurodegenerative disease related to neuroinflammation. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from plants, has been reported to exert various pharmacological effects. However, the neuroprotection of FTS•B related to neuroinflammation has not been systemically reported.MethodsIn amyloid precursor protein/presenilin 1 (APP/PS1) mice, behavioral tests including Morris water maze, Y maze and open field experiment were used to examine the cognitive function. Immunohistochemistry were used to analyze amyloid-beta (Aβ) deposition, Tau protein phosphorylation, the levels of 4-hydroxynonenal (4-HNE), glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (Iba1). Remarkably changed proteins related to neuroinflammation were filtered via proteomics and verified via enzyme-linked immunosorbent assay (ELISA) and western blot. Besides, BV-2 cells and HT22 cells were used to confirm the anti-neuroinflammation of FTS·B.ResultsFTS·B counteracted cognitive decline, ameliorated Aβ deposition and Tau protein phosphorylation, attenuated microglia and astrocytes activation in the cortex and/or hippocampus. Furthermore, FTS·B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase (JIP3/JNK) and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS·B prevented lipopolysaccharide (LPS)-induced neuroinflammation and reduced the microglia-mediated neurotoxicity.ConclusionsFTS·B counteracted cognitive decline by triggering neurogenesis via signaling associated with inflammation, suggesting the promising therapeutic effects of FTS·B on AD treatment.# The two authors contribute equally to the project
A current view on Tau protein phosphorylation in Alzheimer's disease
