Suppressor capacity of copper nanoparticles biosynthesized using Crocus sativus L. leaf aqueous extract on methadone-induced cell death in adrenal phaeochromocytoma (PC12) cell line.
Animals
Antioxidants
/ pharmacology
Cell Survival
/ drug effects
Copper
/ chemistry
Crocus
/ chemistry
Cytokines
/ metabolism
Drug Screening Assays, Antitumor
Inflammation
Inhibitory Concentration 50
Membrane Potential, Mitochondrial
Metal Nanoparticles
/ chemistry
Methadone
/ toxicity
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
PC12 Cells
/ drug effects
Plant Extracts
/ pharmacology
Plant Leaves
/ chemistry
Rats
Spectrophotometry, Ultraviolet
Spectroscopy, Fourier Transform Infrared
X-Ray Diffraction
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
02
04
2020
accepted:
18
06
2020
entrez:
17
7
2020
pubmed:
17
7
2020
medline:
23
1
2021
Statut:
epublish
Résumé
In this research, we prepared and formulated a neuroprotective supplement (copper nanoparticles in aqueous medium utilizing Crocus sativus L. Leaf aqueous extract) for determining its potential against methadone-induced cell death in PC12. The results of chemical characterization tests i.e., FE-SEM, FT-IR, XRD, EDX, TEM, and UV-Vis spectroscopy revealed that the study showed that copper nanoparticles were synthesized in the perfect way possible. In the TEM and FE-SEM images, the copper nanoparticles were in the mean size of 27.5 nm with the spherical shape. In the biological part of the present research, the Rat inflammatory cytokine assay kit was used to measure the concentrations of inflammatory cytokines. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test was used to show DNA fragmentation and apoptosis. Caspase-3 activity was assessed by the caspase activity colorimetric assay kit and mitochondrial membrane potential was studied by Rhodamine123 fluorescence dye. Also, the cell viability of PC12 was measured by trypan blue assay. Copper nanoparticles-treated cell cutlers significantly (p ≤ 0.01) decreased the inflammatory cytokines concentrations, caspase-3 activity, and DNA fragmentation and they raised the cell viability and mitochondrial membrane potential in the high concentration of methadone-treated PC12 cells. The best result of neuroprotective properties was seen in the high dose of copper nanoparticles i.e., 4 µg. According to the above results, copper nanoparticles containing C. sativus leaf aqueous extract can be used in peripheral nervous system treatment as a neuroprotective promoter and central nervous system after approving in the clinical trial studies in humans.
Identifiants
pubmed: 32669563
doi: 10.1038/s41598-020-68142-8
pii: 10.1038/s41598-020-68142-8
pmc: PMC7363853
doi:
Substances chimiques
Antioxidants
0
Cytokines
0
Plant Extracts
0
Copper
789U1901C5
Methadone
UC6VBE7V1Z
Types de publication
Journal Article
Retracted Publication
Langues
eng
Sous-ensembles de citation
IM
Pagination
11631Commentaires et corrections
Type : RetractionIn
Références
Karimi-Maleh, H. vd. Palladium–Nickel nanoparticles decorated on functionalized-MWCNT for high precision non-enzymatic glucose sensing. Mater. Chem. Phys. 250, 123042 (2020).
Karimi-Maleh, H. vd. The role of magnetite/graphene oxide nano-composite as a high-efficiency adsorbent for removal of phenazopyridine residues from water samples, an experimental/theoretical investigation. J. Mol. Liq. 298, 112040 (2020).
Karimi-Maleh, H., Karimi, F., Alizadeh, M. & Sanati, A. L. Electrochemical sensors, a bright future in the fabrication of portable kits in analytical systems. Chem. Rec. https://doi.org/10.1002/tcr.201900092 (2019).
doi: 10.1002/tcr.201900092
pubmed: 31845511
Karimi-Maleh, H., Fakude, C. T., Mabuba, N., Peleyeju, G. M. & Arotiba, O. A. The determination of 2-phenylphenol in the presence of 4-chlorophenol using nano-Fe
pubmed: 31330427
Shamsadin-Azad, Z., Taher, M. A., Cheraghi, S. & Karimi-Maleh, H. A nanostructure voltammetric platform amplified with ionic liquid for determination of tert-butylhydroxyanisole in the presence kojic acid. J. Food Meas. Character. 13, 1781–1787 (2019).
Tahernejad-Javazmi, F., Shabani-Nooshabadi, M. & Karimi-Maleh, H. 3D reduced graphene oxide/FeNi
Experimental and docking theoretical investigations. Khodadadi, A. vd. A new epirubicin biosensor based on amplifying DNA interactions with polypyrrole and nitrogen-doped reduced graphene. Sens. Actuators B Chem. 284, 568–574 (2019).
Miraki, M. vd. Voltammetric amplified platform based on ionic liquid/NiO nanocomposite for determination of benserazide and levodopa. J. Mol. Liq. 278, 672–676 (2019).
Alavi-Tabari, S. A. R., Khalilzadeh, M. A. & Karimi-Maleh, H. Simultaneous determination of doxorubicin and dasatinib as two breast anticancer drugs uses an amplified sensor with ionic liquid and ZnO nanoparticle. J. Electroanal. Chem. 811, 84–88 (2018).
Baghizadeh, A., Karimi-Maleh, H., Khoshnama, Z., Hassankhani, A. & Abbasghorbani, M. A voltammetric sensor for simultaneous determination of vitamin C and vitamin B6 in food samples using ZrO
Jamali, T., Karimi-Maleh, H. & Khalilzadeh, M. A. A novel nanosensor based on Pt:Co nanoalloy ionic liquid carbon paste electrode for voltammetric determination of vitamin B9 in food samples. LWT Food Sci. Technol. 57, 679–685 (2014).
Bijad, M., Karimi-Maleh, H. & Khalilzadeh, M. A. Application of ZnO/CNTs nanocomposite ionic liquid paste electrode as a sensitive voltammetric sensor for determination of ascorbic acid in food samples. Food Anal. Methods 6, 1639–1647 (2013).
Bijad, M., Karimi-Maleh, H., Farsi, M. & Shahidi, S. A. An electrochemical-amplified-platform based on the nanostructure voltammetric sensor for the determination of carmoisine in the presence of tartrazine in dried fruit and soft drink samples. J. Food Meas. Character. 12, 634–640 (2018).
Eren, T., Atar, N., Yola, M. L. & Karimi-Maleh, H. A sensitive molecularly imprinted polymer based quartz crystal microbalance nanosensor for selective determination of lovastatin in red yeast rice. Food Chem. 185, 430–436 (2015).
pubmed: 25952889
Tahernejad-Javazmi, F., Shabani-Nooshabadi, M. & Karimi-Maleh, H. Analysis of glutathione in the presence of acetaminophen and tyrosine via an amplified electrode with MgO/SWCNTs as a sensor in the hemolyzed erythrocyte. Talanta 176, 208–213 (2018).
pubmed: 28917742
Hagh-Nazari, L. vd. Stereological study of kidney in streptozotocin-induced diabetic mice treated with ethanolic extract of Stevia rebaudiana (bitter fraction). Comp. Clin. Pathol. 26, 455–463 (2017).
Zangeneh, M. M., Goodarzi, N., Zangeneh, A., Tahvilian, R. & Najafi, F. Amelioration of renal structural changes in STZ-induced diabetic mice with ethanolic extract of Allium saralicum R.M. Fritsch. Comp. Clin. Pathol. 27, 861–867 (2018).
Sherkatolabbasieh, H. vd. Ameliorative effects of the ethanolic extract of Allium saralicum RM Fritsch on CCl
Tahvilian, R. vd. Green synthesis and chemical characterization of copper nanoparticles using Allium saralicum leaves and assessment of their cytotoxicity, antioxidant, antimicrobial, and cutaneous wound healing properties. Appl. Organomet. Chem. 33 (2019).
Goorani, S. The aqueous extract of Glycyrrhiza glabra effectively prevents induced gastroduodenal ulcers: Experimental study on Wistar rats. Comp. Clin. Pathol. 28, 339–347 (2019).
Goorani, S. vd. Hepatoprotective and cytotoxicity properties of aqueous extract of Glycyrrhiza glabra in Wistar rats fed with high-fat diet. Comp. Clin. Pathol. 28, 1305–1312 (2019).
Zangeneh, A. vd. Therapeutic effects of Glycyrrhiza glabra aqueous extract ointment on cutaneous wound healing in Sprague Dawley male rats. Comp. Clin. Pathol. 28, 1507–1514 (2019).
Srivastava, R., Ahmed, H., Dixit, R., Dharamveer, A. & Saraf, S. Crocus sativus L.: A comprehensive review. Pharmacogn. Rev. 4, 200–208 (2010).
pubmed: 22228962
pmcid: 3249922
McLaughlin, P. J., Levin, R. J. & Zagon, I. S. Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor. Int. J. Oncol. 14, 991–998 (1999).
pubmed: 10200353
Papandreou, M. A. vd. Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection. Behav. Brain Res. 219, 197–204 (2011).
pubmed: 21238492
Hosseinzadeh, H. & Talebzadeh, F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia 76, 722–724 (2005).
pubmed: 16253437
Ochiai, T. vd. Crocin prevents the death of PC-12 cells through sphingomyelinase-ceramide signaling by increasing glutathione synthesis. Neurochem. Int. 44, 321–330 (2004).
pubmed: 14643749
Leppert, W. The role of methadone in cancer pain treatment—a review. Int. J. Clin. Pract. 63, 1095–1109 (2009).
pubmed: 19570126
Perez-Alvarez, S. vd. Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis. Biochim. Biophys. Acta Mol. Basis Dis. 1802, 1036–1047 (2010).
De Vos, J. W. vd. L-methadone and D,L-methadone in methadone maintenance treatment: A comparison of therapeutic effectiveness and plasma concentrations. Eur. Addic. Res. 4, 134–141 (1998).
Quillinan, N., Lau, E. K., Virk, M., Von Zastrow, M. & Williams, J. T. Recovery from μ-opioid receptor desensitization after chronic treatment with morphine and methadone. J. Neurosci. 31, 4434–4443 (2011).
pubmed: 21430144
pmcid: 3092436
Gorman, A. L., Elliott, K. J. & Inturrisi, C. E. The D- and L-isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci. Lett. 223, 5–8 (1997).
pubmed: 9058409
Reig, F., Busquets, M. A., Haro, I., Rabanal, F. & Alsina, M. A. Interaction of opiate molecules with lipid monolayers and liposomes. J. Pharm. Sci. 81, 546–550 (1992).
pubmed: 1522492
Mintzer, M. Z. & Stitzer, M. L. Cognitive impairment in methadone maintenance patients. Drug Alcohol Depend. 67, 41–51 (2002).
pubmed: 12062778
Rass, O. vd. Cognitive performance in methadone maintenance patients: Effects of time relative to dosing and maintenance dose level. Exp. Clin. Psychopharmacol. 22, 248–256 (2014).
pubmed: 24548244
pmcid: 4041803
Vergun, O. vd. Exploration of the role of reactive oxygen species in glutamate neurotoxicity in rat hippocampal neurones in culture. J. Physiol. 531, 147–163 (2001).
pubmed: 11179399
pmcid: 2278451
Trickler, W. J. vd. Effects of copper nanoparticles on rat cerebral microvessel endothelial cells. Nanomedicine 7, 835–846 (2012).
pubmed: 22339089
Mohebbati, R., Khazdair, M. R. & Hedayati, M. Neuroprotective effects of medicinal plants and their constituents neuroprotective effects of medicinal plants and their constituents on different induced neurotoxicity methods: A review. Med. Sci. J. Rep. Pharm. Sci. 6, (2017).
Karimi-Maleh, H. & Arotiba, O. A. Simultaneous determination of cholesterol, ascorbic acid and uric acid as three essential biological compounds at a carbon paste electrode modified with copper oxide decorated reduced graphene oxide nanocomposite and ionic liquid. J. Colloid Interface Sci. 560, 208–212 (2020).
pubmed: 31670018
Karimi-Maleh, H. vd. A novel electrochemical epinine sensor using amplified CuO nanoparticles and a: N-hexyl-3-methylimidazolium hexafluorophosphate electrode. New J. Chem. 43, 2362–2367 (2019).
Cheraghi, S., Taher, M. A. & Karimi-Maleh, H. Highly sensitive square wave voltammetric sensor employing CdO/SWCNTs and room temperature ionic liquid for analysis of vanillin and folic acid in food samples. J. Food Compos. Anal. 62, 254–259 (2017).
Karimi-Maleh, H. vd. Simultaneous determination of 6-mercaptopruine, 6-thioguanine and dasatinib as three important anticancer drugs using nanostructure voltammetric sensor employing Pt/MWCNTs and 1-butyl-3-methylimidazolium hexafluoro phosphate. Biosens. Bioelectron. 86, 879–884 (2016).
pubmed: 27494812
Wang, G. vd Chemical characterization and therapeutic properties of Achillea biebersteinii leaf aqueous extract synthesized copper nanoparticles against methamphetamine-induced cell death in PC12: A study in the nanotechnology and neurology fields. Appl. Organomet. Chem. 34 (2020).
Tahvilian, R. vd. Green synthesis and chemical characterization of copper nanoparticles using Allium saralicum leaves and assessment of their cytotoxicity, antioxidant, antimicrobial, and cutaneous wound healing properties (2019).
Zangeneh, M. M. vd. Novel synthesis of Falcaria vulgaris leaf extract conjugated copper nanoparticles with potent cytotoxicity, antioxidant, antifungal, antibacterial, and cutaneous wound healing activities under in vitro and in vivo condition. J. Photochem. Photobiol. B: Biol. 197, 111556 (2019).
Gurtu, V., Kain, S. R. & Zhang, G. Fluorometric and colorimetric detection of caspase activity associated with apoptosis. Anal. Biochem. 251, 98–102 (1997).
pubmed: 9300088
Strober, W. Trypan blue exclusion test of cell viability. Curr. Protoc. Immunol. 111, A3.B.1-A3.B.3 (2015).
Baracca, A., Sgarbi, G., Solaini, G. & Lenaz, G. Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F(0) during ATP synthesis. Biochem. Biophys. Acta 1606, 137–146 (2003).
pubmed: 14507434
Zhaleh, M. vd. In vitro and in vivo evaluation of cytotoxicity, antioxidant, antibacterial, antifungal, and cutaneous wound healing properties of gold nanoparticles produced via a green chemistry synthesis using Gundelia tournefortii L. as a capping and reducing agent. Appl. Organomet. Chem. 33, e5015 (2019).
Hemmati, S. vd. Green synthesis and characterization of silver nanoparticles using Fritillaria flower extract and their antibacterial activity against some human pathogens. Polyhedron 158, 8–14 (2019).
Cheirmadurai, K., Biswas, S., Murali, R. & Thanikaivelan, P. Green synthesis of copper nanoparticles and conducting nanobiocomposites using plant and animal sources. RSC Adv. 4, 19507–19511 (2014).
Ghidan, A. Y., Al-Antary, T. M. & Awwad, A. M. Green synthesis of copper oxide nanoparticles using Punica granatum peels extract: Effect on green peach Aphid. Environ. Nanotechnol. Monit. Manag. 6, 95–98 (2016).
Sorbiun, M., Shayegan Mehr, E., Ramazani, A. & Taghavi Fardood, S. Green Synthesis of zinc oxide and copper oxide nanoparticles using aqueous extract of oak Fruit Hull (Jaft) and comparing their photocatalytic degradation of basic violet 3. Int. J. Environ. Res. 12, 29–37 (2018).
Taghavi Fardood, S. & Ramazani, A. Green Synthesis and Characterization of Copper Oxide Nanoparticles Using Coffee Powder Extract. J. Nanostruct. 6, 167–171 (2016).
Khani, R., Roostaei, B., Bagherzade, G. & Moudi, M. Green synthesis of copper nanoparticles by fruit extract of Ziziphus spina-christi (L.) Willd.: Application for adsorption of triphenylmethane dye and antibacterial assay. J. Mol. Liq. 255, 541–549 (2018).
Sulaiman, G. M., Tawfeeq, A. T. & Jaaffer, M. D. Biogenic synthesis of copper oxide nanoparticles using olea europaea leaf extract and evaluation of their toxicity activities: An in vivo and in vitro study. Biotechnol. Prog. 34, 218–230 (2018).
pubmed: 28960911
Vaidehi, D., Bhuvaneshwari, V., Bharathi, D. & Sheetal, B. P. Antibacterial and photocatalytic activity of copper oxide nanoparticles synthesized using Solanum lycopersicum leaf extract. Mater. Res. Express 5, 085403 (2018).
Kaur, P., Thakur, R. & Chaudhury, A. Biogenesis of copper nanoparticles using peel extract of Punica granatum and their antimicrobial activity against opportunistic pathogens. Green Chem. Lett. Rev. 9, 33–38 (2016).
Tahvilian, R. vd. Green synthesis and chemical characterization of copper nanoparticles using Allium saralicum leaves and assessment of their cytotoxicity, antioxidant, antimicrobial, and cutaneous wound healing properties. Appl. Organomet. Chem. 33 (2019).
Mukhopadhyay, R., Kazi, J. & Debnath, M. C. Synthesis and characterization of copper nanoparticles stabilized with Quisqualis indica extract: Evaluation of its cytotoxicity and apoptosis in B16F10 melanoma cells. Biomed. Pharmacother. 97, 1373–1385 (2018).
pubmed: 29156527
Beg, S. vd. Metal–organic frameworks as expanding hybrid carriers with diverse therapeutic applications. Organ. Mater. Smart Nanocarriers Drug Deliv. https://doi.org/10.1016/B978-0-12-813663-8.00001-4 (2018).
doi: 10.1016/B978-0-12-813663-8.00001-4
Manuscript, A. Oxidative stress, inflammation, and cancer. Free Radic. Biol. Med. 49, 1603–1616 (2011).
Rehana, D., Mahendiran, D., Kumar, R. S. & Rahiman, A. K. Evaluation of antioxidant and anticancer activity of copper oxide nanoparticles synthesized using medicinally important plant extracts. Biomed. Pharmacother. 89, 1067–1077 (2017).
pubmed: 28292015
Delgado-Povedano, M. del M., Sánchez de Medina, V., Bautista, J., Priego-Capote, F. & Luque de Castro, M. D. Tentative identification of the composition of Agaricus bisporus aqueous enzymatic extracts with antiviral activity against HCV: A study by liquid chromatography-tandem mass spectrometry in high resolution mode. J. Funct. Foods 24, 403–419 (2016).
Jeong, S. C., Koyyalamudi, S. R., Jeong, Y. T., Song, C. H. & Pang, G. Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms. J. Med. Food 15, 58–65 (2012).
pubmed: 22217303
Sankar, R., Maheswari, R., Karthik, S., Shivashangari, K. S. & Ravikumar, V. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles. Mater. Sci. Eng. C 44, 234–239 (2014).
Wildgoose, G. G., Banks, C. E. & Compton, R. G. Metal nanoparticles and related materials supported on Carbon nanotubes: Methods and applications. Small 2, 182–193 (2006).
pubmed: 17193018
Beheshtkhoo, N., Kouhbanani, M. A. J., Savardashtaki, A., Amani, A. M. & Taghizadeh, S. Green synthesis of iron oxide nanoparticles by aqueous leaf extract of Daphne mezereum as a novel dye removing material. Appl. Phys. A Mater. Sci. Process. 124, 1–7 (2018).
Smith, H. S. Opioid metabolism. Mayo Clin. Proc. 84, 613–624 (2009).
pubmed: 19567715
pmcid: 2704133
an experimental long term treatment model. Atici, S. vd. Liver and kidney toxicity in chronic use of opioids. J. Biosci. 30, 245–252 (2005).
Inturrisi, C. E. Pharmacology of methadone and its isomers. Minerva anestesiologica 71, 435–7
Zanin, A. vd. A delayed methadone encephalopathy: Clinical and neuroradiological findings. J. Child Neurol. 25, 748–751 (2010).
Li, W. vd. Methadone-induced damage to white matter integrity in methadone maintenance patients: A longitudinal self-control DTI study. Sci. Rep. 6, 19662 (2016).
pubmed: 26794650
pmcid: 4726264
Cerase, A., Leonini, S., Bellini, M., Chianese, G. & Venturi, C. Methadone-induced toxic leukoencephalopathy: Diagnosis and follow-up by magnetic resonance imaging including diffusion-weighted imaging and apparent diffusion coefficient maps. J. Neuroimaging 21, 283–286 (2011).
pubmed: 20977538
Corré, J., Pillot, J. & Hilbert, G. Methadone-induced toxic brain damage. Case Rep. Radiol. 2013, 602981 (2013).
pubmed: 23762729
pmcid: 3674679
Sotgiu, M. L., Valente, M., Storchi, R., Caramenti, G. & Biella, G. E. M. Cooperative N-methyl-d-aspartate (NMDA) receptor antagonism and μ-opioid receptor agonism mediate the methadone inhibition of the spinal neuron pain-related hyperactivity in a rat model of neuropathic pain. Pharmacol. Res. 60, 284–290 (2009).
pubmed: 19717013
Chan, Y. Y. vd. Inflammatory response in heroin addicts undergoing methadone maintenance treatment. Psychiatry Res. 226, 230–234 (2015).
pubmed: 25660662
Friesen, C., Roscher, M., Alt, A. & Miltner, E. Methadone, commonly used as maintenance medication for outpatient treatment of opioid dependence, kills leukemia cells and overcomes chemoresistance. Can. Res. 68, 6059–6064 (2008).
Kroemer, G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat. Med. 3, 614–620 (1997).
pubmed: 9176486
Kaufmann, S. H. & Earnshaw, W. C. Induction of apoptosis by cancer chemotherapy. Exp. Cell Res. 256, 42–49 (2000).
pubmed: 10739650
Hengartner, M. O. The biochemistry of apoptosis. Nature 407, 770–776 (2000).
pubmed: 11048727
Mousavi, S. H., Tayarani, N. Z. & Parsaee, H. Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in pc12 cells. Cell. Mol. Neurobiol. 30, 185–191 (2010).
pubmed: 19711182
Shati, A. A., Elsaid, F. G. & Hafez, E. E. Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup. Neuroscience 175, 66–74 (2011).
pubmed: 21115102
Sadeghnia, H. R., Kamkar, M., Assadpour, E., Boroushaki, M. T. & Ghorbani, A. Protective effect of safranal, a constituent of Crocus sativus, on quinolinic acid-induced oxidative damage in rat hippocampus. Iran. J. Basic Med. Sci. 16, 73–82 (2013).
pubmed: 23638295
pmcid: 3637907
Hosseinzadeh, H., Sadeghnia, H. R. & Rahimi, A. Effect of safranal on extracellular hippocampal levels of glutamate and aspartate during kainic acid treatment in anesthetized rats. Planta Med. 74, 1441–1445 (2008).
pubmed: 18816431
Bie, X., Chen, Y., Zheng, X. & Dai, H. The role of crocetin in protection following cerebral contusion and in the enhancement of angiogenesis in rats. Fitoterapia 82, 997–1002 (2011).
pubmed: 21741458
Qi, Y. vd. Crocin prevents retinal ischaemia/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K/AKT signalling pathway. Exp. Eye Res. 107, 44–51 (2013).
pubmed: 23201026
Soeda, S. vd. Crocin suppresses tumor necrosis factor-α-induced cell death of neuronally differentiated PC-12 cells. Life Sci. 69, 2887–2898 (2001).
pubmed: 11720092
Yamauchi, M. vd. Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity. Eur. J. Pharmacol. 650, 110–119 (2011).
pubmed: 20951131
Ochiai, T. vd. Crocin prevents the death of PC-12 cells through sphingomyelinase-ceramide signaling by increasing glutathione synthesis. Neurochem. Int. 44, 321–330 (2004).
pubmed: 14643749
Ochiai, T. vd. Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of α-tocopherol. Neurosci. Lett. 362, 61–64 (2004).
pubmed: 15147781
Ochiai, T. vd. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochim. Biophys. Acta Gen. Subj. 1770, 578–584 (2007).
Christensen, T. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses. Rev. Med. Virol. 15, 179–211 (2005).
pubmed: 15782388
Barnett, M. H. & Prineas, J. W. Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion. Ann. Neurol. 55, 458–468 (2004).
pubmed: 15048884
Marciniak, S. J. vd. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18, 3066–3077 (2004).
pubmed: 15601821
pmcid: 535917
Deslauriers, A. M. vd. Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. J. Immunol. 187, 4788–4799 (2011).
pubmed: 21964030
Hosseinzadeh, H. & Jahanian, Z. Effect of Crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice. Phytother. Res. 24, 726–730 (2010).
pubmed: 19827024
Amin, B. & Hosseinzadeh, H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia 83, 888–895 (2012).
pubmed: 22484092