Abstract
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.
Highlights
With the increase in average life expectancy around the world, the old age-related neurological disorders pose a real burden for the modern health care system with huge social-economic impact
Our results show that the treatment of curcumin or cyclocurcumin alone does not affect the viability of the neuronal-like PC12 cells [Fig. 1(a)], inferring that these compounds are not cytotoxic to the differentiated cells within the limits of the concentrations (0.01, 0.1, 1, or 10 μM) used in this study
We studied and compared the effects of cyclocurcumin with curcumin in inhibiting the cytotoxicity of MPP+ in Parkinson’s disease (PD) cell model
Summary
With the increase in average life expectancy around the world, the old age-related neurological disorders pose a real burden for the modern health care system with huge social-economic impact. Researches to find alternative nature-friendly non-toxic medicines to treat cancer and neurodegenerative diseases have attracted increasing attention. One such popularly used herb is the rhizome of turmeric (Curcuma Longa) which has been used in traditional Indian and Chinese medicines for the treatment of various diseases for several centuries and as dietary spices[21,22]. Due to the low toxicity of curcumin and easy availability, it has been studied for potential therapeutic effect against the progression of neurological diseases caused by the formation of aggregated fibrillar protein deposits[31,32,33]. To realize the full potential of cyclocurcumin to treat various diseases, the medicinal properties of this compound deserve further studied
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