Taxifolin prevents β-amyloid-induced impairments of synaptic formation and deficits of memory. - GreenMedInfo Summary
Taxifolin preventsβ-amyloid-induced impairments of synaptic formation and deficits of memory via the inhibition of cytosolic phospholipase A/prostaglandin Econtent.
Metab Brain Dis. 2018 08 ;33(4):1069-1079. Epub 2018 Mar 14. PMID: 29542038
Yuanyuan Wang
Taxifolin is a potent flavonoid with anti-inflammatory activity. Taxifolin has been reported to decrease the accumulation ofβ-amyloid (Aβ), and reduce Aβ-induced neurotoxicity. However, the detail molecular mechanism of taxifolin against Aβ-induced neurotoxicity is largely unknown. In this study, we revealed the protective effects and the underlying mechanisms of taxifolin on the impairments of cognitive function andsynapse formation induced by soluble Aβ oligomers. Our results showed that taxifolin prevented neuronal cell death in a concentration-dependent manner. The recognition memory in novel object recognition tasks and the spatial memory in Morris water maze tests are significantly lower in the Alzheimer's disease (AD) model mice induced by hippocampal injection of Aβ. Taxifolin treatment prevented the recognitive and spatial memory deficits of the AD mice. 10 mg/kg taxifolin treatment also significantly prevented the decreased expression levels of PSD 95 induced by Aβ. Live cell imaging study showed that 2 h pre-treatment of taxifolin prevented the decrease in the number of filopodium and spine induced by Aβoligomers. Aβoligomers significantly increased the production of cytosolic phospholipase A(cPLA), a crucial enzyme of pro-inflammatory mediator, and prostaglandin E(PGE), a neuroinflammatory molecule. Taxifolin significantly reduced the content of cPLAand PGEinduced by Aβboth in the primary hippocampal neurons and hippocampal tissues. These results indicated that taxifolin might prevent Aβoligomer-induced synapse and cognitive impairments through decreasing cPLAand PGE. Our study provided novel insights into the cellular mechanisms for the protective effects of taxifolin on AD.