NEUROPROTECTIVE EFFECTS OF CINNAMON (CINNAMOMUM VERUM) VIA MODULATION OF STRESS RESPONSE SIGNALING
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Emerging scientific evidence corroborates traditional health benefits associated with the use of dietary spices such as cinnamon (Cinnamomum vernum) against chronic, mitogenic, metabolic and aging-related degenerative diseases. However, a comprehensive in vivo evaluation on modulation of physiological homeostatic pathways, imperative to elucidate their true functionality and explain their diverse health promoting effects is lacking. In this thesis I report results from the first ever in vivo study on the effect of cinnamon on stress response signaling in transgenic C. elegans carrying promoter-GFP constructs for several genes in the eukaryotic stress response signaling pathways. Relative fold changes in gene expression in response to cinnamon treatments were quantified by fluorescence microscopy. I found that cinnamon extract mimics insulin like properties and activate insulin signaling. Interestingly I found that cinnamon increased signaling related to redox homeostasis, heat shock proteins, anti-inflammatory, anti-apoptotic and autophagy. However, I also found that cinnamon increased pro-apoptotic and phase I detoxification genes. These finding may suggest beneficial effects of cinnamon on neurodegenerative diseases, but also indicate necessity of proper concentration and fractionations of cinnamon treatment. Excitation neurotoxicity induced dysregulation of stress response signaling has been implicated in neurodegenerative pathologies such as Alzheimer’s disease and Parkinson’s disease. I also evaluated the dose dependent neuroprotective effect of cinnamon in c. elegans model for Alzheimer’s disease and Parkinson’s disease as well as on L-glutamate and NDMA induced excitation toxicity in cultured primary neurons from chick embryos. Results suggest that some fractions of cinnamon were effective in reducing Ab-42 induced neurotoxicity and MPP+ induced paralysis in c. elegans. Cinnamon fractions also decreased neuronal cell death in L-glutamate and NDMA induced excitation toxicity compared to control. Our results suggest a potential neuroprotective effects of bioactive fractions of cinnamon. Further characterization of the bioactive compounds by HPLC/ELSD/MS and investigating their effects in more complex invertebrate and vertebrate models of neurodegeneration are necessary to completely assess the neuroprotective functionality of cinnamon.