crocin and Parkinson-Disease

Parkinson's disease is among the most common forms of neurodegenerative illness, with present treatment being primarily symptomatic and frequently coming with substantial adverse effects. Neuronal degeneration may arise due to a variety of pathological events, like inflammatory responses, neurotransmitter dysregulation, oxidative damage, mitochondrial malfunction, apoptosis, and genetic factors. The health issue and financial burden brought on by Parkinson's disease can worsen as the population ages. In the search for new and secure therapeutic agents for Parkinson's disease, several natural compounds have been shown to exert considerable neuroprotective benefits. Crocin, a naturally occurring carotenoid molecule, was found to have neuroprotective potential in the therapy of this disorder. Taking into account, the outcomes of various studies and the restorative actions of crocin, the present study emphasized the protective ability of crocin in this disease. Given the strong evidence supporting the neuroprotective ability of crocin, it is inferred that crocin inhibits inflammatory, apoptotic, and antioxidant processes through multiple mechanisms. Therefore, this compound is considered a safe and effective therapeutic choice for neurodegenerative illnesses like Parkinson's disease. However, more research on its efficacy as a treatment of Parkinson's disease is needed, specifically examining its mechanisms and the results obtained in clinical trials.

Topics: Antioxidants; Carotenoids; Humans; Neuroprotective Agents; Oxidative Stress; Parkinson Disease

Long-term exposure to organophosphates might result in neurodegenerative diseases, comprising Parkinson's disease. Malathion is an organophosphate pesticide with high neurotoxicity. Oxidative stress, apoptosis, and α-synuclein accumulation are important underlying mechanisms in Parkinson's disease. According to studies, crocin, an active constituent of saffron, has anti-apoptotic, anti-inflammatory, and antioxidant properties. Thus, the effect of crocin on malathion-induced striatal biochemical deficits in rats was investigated in this study. Six groups of male Wistar rats were used: 1. control (normal saline); 2. malathion (100 mg/kg/day, i.p.); 3. crocin (10 mg/kg/day, i.p.) + malathion; 4. levodopa (10 mg/kg/day, i.p.) + malathion; 5. crocin (40 mg/kg/day, i.p.); and 6. polyethylene glycol (PEG) (vehicle of levodopa) groups. The drugs were administered for 28 days. The amounts of Bcl-2, Bax, and caspases 3, 8, and 9 proteins in the striatum were measured by western blotting. Also, the amounts of protein and mRNA level of the α-synuclein in striatum tissue were measured by western blotting and RT-qPCR methods. Malathion induced apoptosis by increasing the amount of Bax/Bcl2 ratio and caspases 3 and 9 proteins in rat striatum tissue. It also increased the protein and mRNA level of α-synuclein in striatal tissue. Co-administration of crocin or levodopa with malathion inhibited the toxic effects of malathion on striatal tissue. Crocin ameliorates the neurotoxic effect of malathion by its anti-apoptotic activity and regulating the expression of proteins involved in Parkinson's disease pathogenesis. As a result, crocin has the potential to be used as a treatment for malathion-induced neurotoxicity.

Topics: alpha-Synuclein; Animals; Anti-Inflammatory Agents; Apoptosis; bcl-2-Associated X Protein; Carotenoids; Levodopa; Malathion; Male; Oxidative Stress; Parkinson Disease; Rats; Rats, Wistar; RNA, Messenger

α-Synuclein is a presynaptic neuronal protein that is abundant in the human brain and is linked genetically and neuropathologically to Parkinson's disease (PD). The E46K mutation of the α-synuclein gene has been linked to autosomal dominant early-onset of PD. Crocin is a carotenoid chemical compound of saffron that has been shown antioxidant and neural protective activity. This study examined the effect of Crocin in preventing the amyloid fibril in the E46K α-synuclein, through in vitro studies and computational simulations. The result demonstrated that Crocin acts as a molecular chaperone to prevent amyloid fibril formation of E46K α-synuclein in a concentration-dependent manner. In fact, Crocin redirects E46K α-synuclein from a fibril-formation pathway towards an amorphous aggregation pathway or at least reduce its aggregation tendency. Combined results from molecular dynamics and docking studies indicate that the inhibitory effect of the Crocin may be due to binding of the Crocin with the hydrophobic region (contact interface) of the α-synuclein which has the propensity to form amyloid aggregate. The results indicated Crocin can potentially bind to the C-terminal and mainly NAC (central hydrophobic region) domain of the E46K α-synuclein, and stabilizes the protein by masking the polymerization hotspot and consequently converting the protein into amyloid fibrils. These results support that Crocin is a effective inhibitor of E46K α-synuclein fibrillization and it could be considered as a potential therapeutic agent in the treatment of Parkinson disease.

Topics: alpha-Synuclein; Amyloid; Carotenoids; Computer Simulation; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Mutation; Neurons; Parkinson Disease; Spectrometry, Fluorescence

The purpose of the present study was to investigate the effect of crocin on brain oxidative damage and memory deficits in a 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Male Wistar rats were subjected to unilateral injection of 6-OHDA (16 µg) into the medial forebrain bundle and treated with crocin (30 and 60 mg/kg) for six weeks. The rats were tested for memory performance at six weeks after 6-OHDA infusion, and then were killed for the estimation of biochemical parameters. The increase in thiobarbituric acid reactive substances (TBARS) and nitrite levels in the hippocampus were observed in the 6-OHDA lesioned rats, which was accompanied by memory deficits in a passive avoidance test at the end of week 6. Moreover, treatment with crocin decreased TBARS and nitrite levels in the hippocampus, and improved aversive memory. The present study conclusively demonstrated that crocin acts as an antioxidant and anti-inflammatory agent in the hippocampus of parkinsonian rats and could improve aversive memory through its properties.

Topics: Animals; Antioxidants; Carotenoids; Cerebral Cortex; Disease Models, Animal; Glutathione Peroxidase; Lipid Peroxidation; Male; Memory; Memory Disorders; Nitrites; Oxidative Stress; Oxidopamine; Parkinson Disease; Random Allocation; Rats, Wistar; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances

The molecular machinery that mediates neuronal injury in neurodegenerative conditions such as Parkinson's disease (PD) remains to be fully deciphered, which will hopefully provide novel therapeutic targets for these disorders. Crocin, one of the water-soluble carotenoids isolated from the Crocus sativus L (saffron) stigma, has been reported to exert therapeutic potential in many disease models. Here, we establish an in vitro PD model using 1-methyl-4-phenylpyridinium (MPP(+))-injured PC12 cells to investigate the protective effects of crocin. Crocin treatment significantly attenuated MPP(+)-induced cell injury and apoptosis with little toxicity, and these protective effects were still observed even if crocin treatment was delayed to 6 h after injury. Crocin also inhibited MPP(+)-induced mitochondrial dysfunction, as evidenced by preservation of mitochondrial membrane potential (MMP) and ATP synthesis, which correlates with suppressed endoplasmic reticulum (ER) stress through inhibiting ER chaperone and ER related apoptotic factors. In addition, ER calcium release and morphological changes in ER lumen after MPP(+) exposure were all partially prevented by crocin. By using specific targeted small interfering RNA (siRNA) to knockdown the expression of the C/EBP homologous protein (CHOP), we found that crocin-induced protection and inhibition of ER stress was mediated by inverting MPP(+)-induced decrease of Wnt through the CHOP pathway. Our study demonstrates a pivotal role of ER stress in mediating PD related neuronal injury via the regulation of CHOP-Wnt pathway, and suggests the therapeutic values of crocin against ER stress-associated cytotoxicity.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Carotenoids; Cell Survival; Cytoprotection; Dose-Response Relationship, Drug; Endoplasmic Reticulum Stress; Membrane Potential, Mitochondrial; Mitochondria; Parkinson Disease; PC12 Cells; Rats