Neuroprotective effect of three caffeic acid derivatives via ameliorate oxidative stress and enhance PKA/CREB signaling pathway

Abstract This study was conducted to elucidate the neuroprotective effect of caffeic acid phenethyl ester (CAPE), ( R )-2-Hydroxy-3-(3,4-dihydroxyphenyl) propionic acid (Danshensu) and Curcumin, three caffeic acid derivatives which are contained in fruits, grains and certain dietary supplements. Our results showed that these compounds significantly attenuated H 2 O 2 -induced toxicity in PC12 cells in a dose-dependent manner. Furthermore, these compounds significantly improved the behavioral performance of d -gal-treated mice in both step-down avoidance test and Morris water maze test. Biochemical examination and western blot analysis showed that these compounds could ameliorate oxidative stress and facilitate activation of the protein kinase A (PKA)-cyclic AMP response element-binding protein (CREB) pathway. Its beneficial effects may partly relate to enhancing the activity of endogenous antioxidant enzymes and modulating the PKA/CREB signaling pathway. Furthermore, our results also indicated that the presence of 3, 4-dihydroxyphenyl groups in A ring may enhance their neuroprotective activity.