trans-sodium-crocetinate and Retinal-Degeneration

Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. α-Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linné (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of α-synuclein and promoted the dissociation of α-synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant α-synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated α-synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in the eye of A30P fly PD model. Saffron had a cytoprotective effect on a human neuronal cell line with α-synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD.

Topics: alpha-Synuclein; Animals; Animals, Genetically Modified; Carotenoids; Cell Line; Crocus; Disease Models, Animal; Drosophila melanogaster; Female; Humans; Longevity; Male; Motor Activity; Mutation; Neurons; Neuroprotective Agents; Parkinson Disease; Retinal Degeneration; Vitamin A

Topics: Adenosine Triphosphate; Animals; Calcium; Carotenoids; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Crocus; Disease Models, Animal; Flowers; HEK293 Cells; Humans; Light; Mice; Neurodegenerative Diseases; Neuroprotective Agents; Plant Extracts; Rats, Sprague-Dawley; Receptors, Purinergic P2X7; Retina; Retinal Degeneration; Vitamin A

Crocetin is a carotenoid that is the aglicone of crocin, which are found in saffron stigmas (Crocus sativus L.) and gardenia fruit (Gardenia jasminoides Ellis). In this study, we investigated the effects of crocetin on retinal damage. To examine whether crocetin affects stress pathways, we investigated intracellular oxidation induced by reactive oxygen species, expression of endoplasmic reticulum (ER) stress-related proteins, disruption of the mitochondrial membrane potential (ΔΨ(m)), and caspases activation. In vitro, we employed cultured retinal ganglion cells (RGC-5, a mouse ganglion cell-line transformed using E1A virus). Cell damage was induced by tunicamycin or hydrogen peroxide (H(2)O(2)) exposure. Crocetin at a concentration of 3μM showed the inhibitory effect of 50-60% against tunicamycin- and H(2)O(2)-induced cell death and inhibited increase in caspase-3 and -9 activity. Moreover, crocetin inhibited the enzymatic activity of caspase-9 in a cell-free system. In vivo, retinal damage in mice was induced by exposure to white light at 8000lx for 3h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5days after light exposure and recording the electroretinogram (ERG). Retinal cell damage was also detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at 48h after light exposure. Crocetin at 100mg/kg, p.o. significantly inhibited photoreceptor degeneration and retinal dysfunction and halved the expression of TUNEL-positive cells. These results indicate that crocetin has protective effects against retinal damage in vitro and in vivo, suggesting that the mechanism may inhibit increase in caspase-3 and -9 activities after retinal damage.

Topics: Administration, Oral; Animals; Carotenoids; Caspase Inhibitors; Caspases; Cell Death; Cell Line; Chromans; Endoplasmic Reticulum; Enzyme Activation; Enzyme Inhibitors; Fluoresceins; Gene Expression Regulation; Humans; Hydrogen Peroxide; Intracellular Space; Light; Male; Membrane Potential, Mitochondrial; Mice; Oxidation-Reduction; Oxidative Stress; Photoreceptor Cells, Vertebrate; Rats; Retinal Degeneration; Retinal Ganglion Cells; Tunicamycin; Vitamin A; Xanthenes