Harnessing phytochemicals to protect the brain

In recent years, there has been increased interest in plants as a source of bioactive molecules that might be developed into drugs for the treatment of various diseases. Moreover, phytochemicals have inspired conventional drug development. Oxidative stress and amyloid beta toxicity are involved in the pathogenesis of Alzheimer`s disease. We have previously demonstrated that an extract prepared of the plant Achillea fragrantissima (Af) protected cultured brain astrocytes from oxidative stress-induced cell death and down-regulated microglial activation. Using activity-guided fractionation, we have purified from Af an active flavonoid named 3,5,4’-trihydroxy-6,7,3’-trimethoxyflavone (TTF). TTF protected cultured astrocytes from H2O2 –induced cell death via interference with cell signaling (inhibition of SAPK/JNK, ERK 1/2, and MEK1 phosphorylation) and by reducing the levels of oxidative stress-induced reactive oxygen species (ROS). In addition, TTF protected cultured neuronal cells from amyloid beta cytotoxicity via interference with cell signaling events and by reducing the amyloid beta-induced levels of intracellular ROS. Moreover, TTF exhibited anti-inflammatory activities and inhibited the LPS-elicited secretion of the proinflammatory cytokines Interleukin 6 (IL-6) and IL-1beta from microglial cells. Based on its beneficial effects, future studies should examine the potential use of TTF in the treatment of neurodegenerative diseases that involve Aβ toxicity, neuroinflammation, and oxidative stress.