Inhibitory effects of curcumin and cyclocurcumin in 1-methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in differentiated PC12 cells

Development and progression of neurodegenerative diseases like Parkinson's disease (PD) involve multiple pathways. Thus, effective therapeutic treatments should intervene to address all these pathways simultaneously for greater success. Most of the current pharmacotherapeutic approaches just supplement striatal dopamine. Hence, natural extracts of plants with therapeutic potential have been explored. Curcuminoids belong to one such group of polyphenol which show immense therapeutic effects. Here, we have used intracellular reactive oxygen species (ROS) measurement, and two-photon fluorescence lifetime imaging microscopy (2P-FLIM) of cellular autofluorescent co-enzyme reduced nicotinamide adenine dinucleotide (NADH) to study the inhibitory effects of curcumin and cyclocurcumin in alleviating PD like neurotoxicity of 1-methyl-4-phenylpyridinium (MPP+) in neuronal growth factor (NGF) induced differentiated PC12 cells. Our results showed that both cyclocurcumin and curcumin reduced the level of ROS caused by MPP+ treatment. Moreover, a significant increase in the free, protein-bound, and average NADH fluorescence lifetimes along with a decrease in the relative contribution of free- vs. protein-bound NADH components in curcuminoids treated cells (pretreated with MPP+) were observed compared with those treated with MPP+ only. This study, which indicates that cyclocurcumin offers higher neuronal protection than curcumin, may initiate further studies of these compounds in the cure of neurodegenerative diseases.