STUDY OF THE ANTI-INFLAMMATORY ACTIVITY OF NOVEL TACRINE DERIVATIVES WITH LIPIDS EXTRACTED FROM CASHEW NUT SHELL LIQUID

Neurodegenerative diseases, including Alzheimer’s disease (AD), are associated with neuroinflammation which initiates the degeneration of neurons by over-activating microglia in the brain. It is now widely accepted that clustered populations of reactive microglia are hallmarks of AD, and these brain cells are likely to contribute to the mechanisms of neuronal damage and cognitive loss. Therefore, the prevention and/or modulation of key pro- inflammatory molecules from microglia is a promising strategy for the prevention and possible treatment of AD. In the present study, the anti-inflammatory activity of eight novel synthetized compounds obtained derivatizing tacrine with lipids extracted from cashew nut shell liquid was assessed in BV-2 microglial cells. Cells were treated with different concentrations of the compounds for 24 h, then exposed to LPS and cell viability evaluated by MTT assay. Only 5 of the tested compounds were able to significantly counteract the reduction of cell viability induced by LPS. To verify if this protection could be ascribed to an anti-inflammatory mechanism, real time PCR analysis were carried out to assess the expression of interleukin 1 and TNF-alfa. All of the 5 compounds were able to significantly reduce interleukin 1 expression, while only 4 compounds reduced TNF-alfa expression. These results suggest a therapeutic potential of these compounds as novel anti-inflammatory drugs in neurodegenerative diseases, mediating favorable modulation of pro-inflammatory functions of microglia.