Antioxidant Properties of Crocus Sativus L. and Its Constituents and Relevance to Neurodegenerative Diseases; Focus on Alzheimer’s and Parkinson’s Disease

Author(s): Kyriaki Hatziagapiou*, Eleni Kakouri, George I. Lambrou*, Kostas Bethanis, Petros A. Tarantilis.

Journal Name: Current Neuropharmacology

Volume 17 , Issue 4 , 2019

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Graphical Abstract:


Abstract:

Background: Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen-nitrogen species, are the inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants, there is growing interest in Crocus Sativus L. It is a perennial, stemless herb, belonging to Iridaceae family, cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China, Egypt and Mexico.

Objective: The present study aims to address the protective role of Crocus Sativus L. in neurodegeneration with an emphasis in Parkinson’s and Alzheimer’s disease.

Materials and Methods: An electronic literature search was conducted by two of the authors from 1993 to August 2017. Original articles and systematic reviews (with or without meta-analysis), as well as case reports were selected. Titles and abstracts of papers were screened by a third reviewer to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved.

Results: Hence, the authors focused on the literature concerning the role of Crocus Sativus L. on its anti-oxidant and neuroprotective properties.

Conclusion: Literature findings represented in current review herald promising results for using Crocus Sativus L. and/or its active constituents as antioxidants, anti-inflammatory, and neuroprotective agents.

Keywords: Saffron, crocin, crocetin, safranal, oxidative stress, neurodegeneration, Alzheimer’s disease, Parkinson's disease.

[1]
Ozcan, A.; Ogun, M.; Gowder, S.J.T. Biochemistry of Reactive Oxygen and Nitrogen Species; Basic Principles and Clinical Significance of Oxidative Stress, 2015, pp. 38-54.
[http://dx.doi.org/10.5772/61193]
[2]
Ahmadinejad, F.; Geir Møller, S.; Hashemzadeh-Chaleshtori, M.; Bidkhori, G.; Jami, M.S. Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress. Antioxidants, 2017, 6(3), 51.
[http://dx.doi.org/10.3390/antiox6030051] [PMID: 28698499]
[3]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[4]
Ye, Z.W.; Zhang, J.; Townsend, D.M.; Tew, K.D. Oxidative stress, redox regulation and diseases of cellular differentiation. Biochim. Biophys. Acta, 2015, 1850(8), 1607-1621.
[http://dx.doi.org/10.1016/j.bbagen.2014.11.010] [PMID: 25445706]
[5]
Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol., 2014, 24(10), R453-R462.
[http://dx.doi.org/10.1016/j.cub.2014.03.034] [PMID: 24845678]
[6]
Lushchak, V.I. Free radicals, reactive oxygen species, oxidative stress and its classification. Chem. Biol. Interact., 2014, 224, 164-175.
[http://dx.doi.org/10.1016/j.cbi.2014.10.016] [PMID: 25452175]
[7]
Busik, J.V.; Mohr, S.; Grant, M.B. Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators. Diabetes, 2008, 57(7), 1952-1965.
[http://dx.doi.org/10.2337/db07-1520] [PMID: 18420487]
[8]
Andreoli, T.E. Free radicals and oxidative stress. Am. J. Med., 2000, 108(8), 650-651.
[http://dx.doi.org/10.1016/S0002-9343(00)00418-6] [PMID: 10856413]
[9]
Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30(1), 11-26.
[http://dx.doi.org/10.1007/s12291-014-0446-0] [PMID: 25646037]
[10]
Reczek, C.R.; Chandel, N.S. ROS-dependent signal transduction. Curr. Opin. Cell Biol., 2015, 33, 8-13.
[http://dx.doi.org/10.1016/j.ceb.2014.09.010] [PMID: 25305438]
[11]
Villanueva, C.; Giulivi, C. Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease. Free Radic. Biol. Med., 2010, 49(3), 307-316.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.04.004] [PMID: 20388537]
[12]
Forstermann, U.; Sessa, W.C. Nitric oxide synthases: regulation and function. Eur. Heart J., 2012, 33(7), 829-837.
[http://dx.doi.org/10.1093/eurheartj/ehr304]
[13]
Giacco, F.; Brownlee, M. Oxidative stress and diabetic complications. Circ. Res., 2010, 107(9), 1058-1070.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.223545] [PMID: 21030723]
[14]
Bar-Or, D.; Bar-Or, R.; Rael, L.T.; Brody, E.N. Oxidative stress in severe acute illness. Redox Biol., 2015, 4, 340-345.
[http://dx.doi.org/10.1016/j.redox.2015.01.006] [PMID: 25644686]
[15]
Sies, H. Oxidative stress: a concept in redox biology and medicine. Redox Biol., 2015, 4, 180-183.
[http://dx.doi.org/10.1016/j.redox.2015.01.002] [PMID: 25588755]
[16]
Liu, Z.; Zhou, T.; Ziegler, A.C.; Dimitrion, P.; Zuo, L. Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications. Oxid. Med. Cell. Longev., 2017, 2017, 2525967.
[http://dx.doi.org/10.1155/2017/2525967] [PMID: 28785371]
[17]
Cobb, C.A.; Cole, M.P. Oxidative and nitrative stress in neurodegeneration. Neurobiol. Dis., 2015, 84(Suppl. C), 4-21.
[http://dx.doi.org/10.1016/j.nbd.2015.04.020] [PMID: 26024962]
[18]
Guo, C.; Sun, L.; Chen, X.; Zhang, D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen. Res., 2013, 8(21), 2003-2014.
[PMID: 25206509]
[19]
Pamplona, R. Membrane phospholipids, lipoxidative damage and molecular integrity: a causal role in aging and longevity. Biochim. Biophys. Acta, 2008, 1777(10), 1249-1262.
[http://dx.doi.org/10.1016/j.bbabio.2008.07.003] [PMID: 18721793]
[20]
Ljubisavljevic, S. Oxidative Stress and Neurobiology of Demyelination. Mol. Neurobiol., 2016, 53(1), 744-758.
[http://dx.doi.org/10.1007/s12035-014-9041-x] [PMID: 25502298]
[21]
Dasuri, K.; Zhang, L.; Keller, J.N. Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic. Biol. Med., 2013, 62, 170-185.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.09.016] [PMID: 23000246]
[22]
Fakhruddin, S.; Alanazi, W.; Jackson, K.E. Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury. J. Diabetes Res., 2017, 2017, 8379327.
[http://dx.doi.org/10.1155/2017/8379327] [PMID: 28164134]
[23]
Yan, L.J. Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J. Diabetes Res., 2014, 2014, 137919.
[http://dx.doi.org/10.1155/2014/137919] [PMID: 25019091]
[24]
Adibhatla, R.M.; Hatcher, J.F. Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal., 2010, 12(1), 125-169.
[http://dx.doi.org/10.1089/ars.2009.2668] [PMID: 19624272]
[25]
Jnaneshwari, S.; Hemshekhar, M.; Santhosh, M.S.; Sunitha, K.; Thushara, R.; Thirunavukkarasu, C.; Kemparaju, K.; Girish, K.S. Crocin, a dietary colorant, mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines. J. Pharm. Pharmacol., 2013, 65(4), 604-614.
[http://dx.doi.org/10.1111/jphp.12016] [PMID: 23488790]
[26]
Collard, C.D.; Gelman, S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology, 2001, 94(6), 1133-1138.
[http://dx.doi.org/10.1097/00000542-200106000-00030] [PMID: 11465607]
[27]
Massaad, C.A. Neuronal and vascular oxidative stress in Alzheimer’s disease. Curr. Neuropharmacol., 2011, 9(4), 662-673.
[http://dx.doi.org/10.2174/157015911798376244] [PMID: 22654724]
[28]
Thapa, A.; Carroll, N.J. Dietary Modulation of Oxidative Stress in Alzheimer’s Disease. Int. J. Mol. Sci., 2017, 18(7), E1583.
[http://dx.doi.org/10.3390/ijms18071583] [PMID: 28753984]
[29]
Bathaie, S.Z.; Mousavi, S.Z. New applications and mechanisms of action of saffron and its important ingredients. Crit. Rev. Food Sci. Nutr., 2010, 50(8), 761-786.
[http://dx.doi.org/10.1080/10408390902773003] [PMID: 20830635]
[30]
Chiavaroli, A.; Recinella, L.; Ferrante, C.; Locatelli, M.; Carradori, S.; Macchione, N.; Zengin, G.; Leporini, L.; Leone, S.; Martinotti, S.; Brunetti, L.; Vacca, M.; Menghini, L.; Orlando, G. Crocus sativus, Serenoa repens and Pinus massoniana extracts modulate inflammatory response in isolated rat prostate challenged with LPS. J. Biol. Regul. Homeost. Agents, 2017, 31(3), 531-541.
[PMID: 28889734]
[31]
De Monte, C.; Bizzarri, B.; Gidaro, M.C.; Carradori, S.; Mollica, A.; Luisi, G.; Granese, A.; Alcaro, S.; Costa, G.; Basilico, N.; Parapini, S.; Scaltrito, M.M.; Masia, C.; Sisto, F. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents. J. Enzyme Inhib. Med. Chem., 2015, 30(6), 1027-1033.
[http://dx.doi.org/10.3109/14756366.2014.1001755] [PMID: 25766747]
[32]
Rahaiee, S.; Moini, S.; Hashemi, M.; Shojaosadati, S.A. Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review. J. Food Sci. Technol., 2015, 52(4), 1881-1888.
[http://dx.doi.org/10.1007/s13197-013-1238-x] [PMID: 25829569]
[33]
Finley, J.W.; Gao, S. A Perspective on Crocus sativus L. (Saffron) Constituent Crocin: A Potent Water-Soluble Antioxidant and Potential Therapy for Alzheimer’s Disease. J. Agric. Food Chem., 2017, 65(5), 1005-1020.
[http://dx.doi.org/10.1021/acs.jafc.6b04398] [PMID: 28098452]
[34]
Patel, S.; Sarwat, M.; Khan, T.H. Mechanism behind the anti-tumour potential of saffron (Crocus sativus L.): The molecular perspective. Crit. Rev. Oncol. Hematol., 2017, 115, 27-35.
[http://dx.doi.org/10.1016/j.critrevonc.2017.04.010] [PMID: 28602167]
[35]
Christodoulou, E.; Kadoglou, N.P.; Kostomitsopoulos, N.; Valsami, G. Saffron: a natural product with potential pharmaceutical applications. J. Pharm. Pharmacol., 2015, 67(12), 1634-1649.
[http://dx.doi.org/10.1111/jphp.12456] [PMID: 26272123]
[36]
Hosseinzadeh, H.; Sadeghnia, H.R. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J. Pharm. Pharm. Sci., 2005, 8(3), 394-399.
[PMID: 16401389]
[37]
Ayatollahi, H.; Javan, A.O.; Khajedaluee, M.; Shahroodian, M.; Hosseinzadeh, H. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytother. Res., 2014, 28(4), 539-543.
[http://dx.doi.org/10.1002/ptr.5021] [PMID: 23733488]
[38]
Mehdizadeh, R.; Parizadeh, M.R.; Khooei, A.R.; Mehri, S.; Hosseinzadeh, H. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in wistar rats. Iran. J. Basic Med. Sci., 2013, 16(1), 56-63.
[PMID: 23638293]
[39]
Khorasany, A.R.; Hosseinzadeh, H. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review. Iran. J. Basic Med. Sci., 2016, 19(5), 455-469.
[PMID: 27403251]
[40]
Azimi, P.; Ghiasvand, R.; Feizi, A.; Hosseinzadeh, J.; Bahreynian, M.; Hariri, M.; Khosravi-Boroujeni, H. Effect of cinnamon, cardamom, saffron and ginger consumption on blood pressure and a marker of endothelial function in patients with type 2 diabetes mellitus: A randomized controlled clinical trial. Blood Press., 2016, 25(3), 133-140.
[http://dx.doi.org/10.3109/08037051.2015.1111020] [PMID: 26758574]
[41]
Imenshahidi, M.; Hosseinzadeh, H.; Javadpour, Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother. Res., 2010, 24(7), 990-994.
[PMID: 20013822]
[42]
Imenshahidi, M.; Razavi, B.M.; Faal, A.; Gholampoor, A.; Mousavi, S.M.; Hosseinzadeh, H. The Effect of Chronic Administration of Saffron (Crocus sativus) Stigma Aqueous Extract on Systolic Blood Pressure in Rats. Jundishapur J. Nat. Pharm. Prod., 2013, 8(4), 175-179.
[http://dx.doi.org/10.17795/jjnpp-12475] [PMID: 24624210]
[43]
Amin, B.; Abnous, K.; Motamedshariaty, V.; Hosseinzadeh, H. Attenuation of oxidative stress, inflammation and apoptosis by ethanolic and aqueous extracts of Crocus sativus L. stigma after chronic constriction injury of rats. An. Acad. Bras. Cienc., 2014, 86(4), 1821-1832.
[http://dx.doi.org/10.1590/0001-3765201420140067] [PMID: 25590719]
[44]
Amin, B.; Malekzadeh, M.; Heidari, M.R.; Hosseinzadeh, H. Effect of Crocus sativus extracts and its active constituent safranal on the harmaline-induced tremor in mice. Iran. J. Basic Med. Sci., 2015, 18(5), 449-458.
[PMID: 26124930]
[45]
Amin, B.; Nakhsaz, A.; Hosseinzadeh, H. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice. Avicenna J. Phytomed., 2015, 5(5), 458-468.
[PMID: 26468466]
[46]
De Monte, C.; Carradori, S.; Chimenti, P.; Secci, D.; Mannina, L.; Alcaro, F.; Petzer, A.; N’Da, C.I.; Gidaro, M.C.; Costa, G.; Alcaro, S.; Petzer, J.P. New insights into the biological properties of Crocus sativus L. Chemical modifications, human monoamine oxidases inhibition and molecular modeling studies. Eur. J. Med. Chem., 2014, 82, 164-171.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.048] [PMID: 24904963]
[47]
Ghasemi, T.; Abnous, K.; Vahdati, F.; Mehri, S.; Razavi, B.M.; Hosseinzadeh, H. Antidepressant Effect of Crocus sativus Aqueous Extract and its Effect on CREB, BDNF, and VGF Transcript and Protein Levels in Rat Hippocampus. Drug Res. (Stuttg.), 2015, 65(7), 337-343.
[PMID: 24696423]
[48]
Hosseinzadeh, H. Saffron: a herbal medicine of third millennium. Jundishapur J. Nat. Pharm. Prod., 2014, 9(1), 1-2.
[http://dx.doi.org/10.17795/jjnpp-16700] [PMID: 24644431]
[49]
Hosseinzadeh, H.; Ghenaati, J. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia, 2006, 77(6), 446-448.
[http://dx.doi.org/10.1016/j.fitote.2006.04.012] [PMID: 16814486]
[50]
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., 2010, 24(5), 726-730.
[PMID: 19827024]
[51]
Hosseinzadeh, H.; Modaghegh, M.H.; Saffari, Z. Crocus sativus L. (Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid. Based Complement. Alternat. Med., 2009, 6(3), 343-350.
[http://dx.doi.org/10.1093/ecam/nem125] [PMID: 18955256]
[52]
Hosseinzadeh, H.; Noraei, N.B. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother. Res., 2009, 23(6), 768-774.
[http://dx.doi.org/10.1002/ptr.2597] [PMID: 19142981]
[53]
Hosseinzadeh, H.; Sadeghnia, H.R.; Ghaeni, F.A.; Motamedshariaty, V.S.; Mohajeri, S.A. Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother. Res., 2012, 26(3), 381-386.
[PMID: 21774008]
[54]
Hosseinzadeh, H.; Sadeghnia, H.R.; Ziaee, T.; Danaee, A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J. Pharm. Pharm. Sci., 2005, 8(3), 387-393.
[PMID: 16401388]
[55]
Hosseinzadeh, H.; Younesi, H.M. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol., 2002, 2, 7.
[http://dx.doi.org/10.1186/1471-2210-2-7] [PMID: 11914135]
[56]
Okada, T.; Yamada, N.; Tsuzuki, K.; Horikawa, H.P.; Tanaka, K.; Ozawa, S. Long-term potentiation in the hippocampal CA1 area and dentate gyrus plays different roles in spatial learning. Eur. J. Neurosci., 2003, 17(2), 341-349.
[http://dx.doi.org/10.1046/j.1460-9568.2003.02458.x] [PMID: 12542671]
[57]
Sugiura, M.; Shoyama, Y.; Saito, H.; Nishiyama, N. Crocin improves the ethanol-induced impairment of learning behaviors of mice in passive avoidance tasks. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 1995, 71(10), 319-324.
[58]
Winterhalter, P.; Straubinger, M. Saffron-renewed interest in an ancient spice. Food Rev. Int., 2000, 16(1), 39-59.
[http://dx.doi.org/10.1081/FRI-100100281]
[59]
Alavizadeh, S.H.; Hosseinzadeh, H. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem. Toxicol., 2014, 64, 65-80.
[http://dx.doi.org/10.1016/j.fct.2013.11.016] [PMID: 24275090]
[60]
Liakopoulou-Kyriakides, M.; Kyriakidis, D.A. Croscus sativus-biological active constitutents. Studies Nat. Products Chem., 2002, 26, 293-312.
[http://dx.doi.org/10.1016/S1572-5995(02)80009-6]
[61]
Bolhassani, A.; Khavari, A.; Bathaie, S.Z. Saffron and natural carotenoids: Biochemical activities and anti-tumor effects. Biochim. Biophys. Acta, 2014, 1845(1), 20-30.
[PMID: 24269582]
[62]
Caballero-Ortega, H.; Pereda-Miranda, R.; Abdullaev, F.I. HPLC quantification of major active components from 11 different saffron (Crocus sativus L.) sources. Food Chem., 2007, 100(3), 1126-1131.
[http://dx.doi.org/10.1016/j.foodchem.2005.11.020]
[63]
Giaccio, M. Crocetin from saffron: an active component of an ancient spice. Crit. Rev. Food Sci. Nutr., 2004, 44(3), 155-172.
[http://dx.doi.org/10.1080/10408690490441433] [PMID: 15239370]
[64]
Assimopoulou, A.N.; Sinakos, Z.; Papageorgiou, V.P. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother. Res., 2005, 19(11), 997-1000.
[http://dx.doi.org/10.1002/ptr.1749] [PMID: 16317646]
[65]
Tarantilis, P.A.; Tsoupras, G.; Polissiou, M. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry. J. Chromatogr. A, 1995, 699(1-2), 107-118.
[http://dx.doi.org/10.1016/0021-9673(95)00044-N] [PMID: 7757208]
[66]
Rahaiee, S.; Hashemi, M.; Shojaosadati, S.A.; Moini, S.; Razavi, S.H. Nanoparticles based on crocin loaded chitosan-alginate biopolymers: Antioxidant activities, bioavailability and anticancer properties. Int. J. Biol. Macromol., 2017, 99, 401-408.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.02.095] [PMID: 28254570]
[67]
Gutheil, W.G.; Reed, G.; Ray, A.; Anant, S.; Dhar, A. Crocetin: An agent derived from saffron for prevention and therapy for cancer. Curr. Pharm. Biotechnol., 2012, 13(1), 173-179.
[http://dx.doi.org/10.2174/138920112798868566] [PMID: 21466430]
[68]
Rezaee, R.; Hosseinzadeh, H. Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran. J. Basic Med. Sci., 2013, 16(1), 12-26.
[PMID: 23638289]
[69]
Papandreou, M.A.; Kanakis, C.D.; Polissiou, M.G.; Efthimiopoulos, S.; Cordopatis, P.; Margarity, M.; Lamari, F.N. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J. Agric. Food Chem., 2006, 54(23), 8762-8768.
[http://dx.doi.org/10.1021/jf061932a] [PMID: 17090119]
[70]
Serrano-Díaz, J.; Sánchez, A.M.; Maggi, L.; Martínez-Tomé, M.; García-Diz, L.; Murcia, M.A.; Alonso, G.L. Increasing the applications of Crocus sativus flowers as natural antioxidants. J. Food Sci., 2012, 77(11), C1162-C1168.
[http://dx.doi.org/10.1111/j.1750-3841.2012.02926.x] [PMID: 23057806]
[71]
Karimi, E.; Oskoueian, E.; Hendra, R.; Jaafar, H.Z. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules, 2010, 15(9), 6244-6256.
[http://dx.doi.org/10.3390/molecules15096244] [PMID: 20877220]
[72]
Amin, A.; Hamza, A.A.; Bajbouj, K.; Ashraf, S.S.; Daoud, S. Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology, 2011, 54(3), 857-867.
[http://dx.doi.org/10.1002/hep.24433] [PMID: 21607999]
[73]
Kanakis, C.D.; Tarantilis, P.A.; Pappas, C.; Bariyanga, J.; Tajmir-Riahi, H.A.; Polissiou, M.G. An overview of structural features of DNA and RNA complexes with saffron compounds: Models and antioxidant activity. J. Photochem. Photobiol. B, 2009, 95(3), 204-212.
[http://dx.doi.org/10.1016/j.jphotobiol.2009.03.006] [PMID: 19395270]
[74]
Kanakis, C.D.; Tarantilis, P.A.; Tajmir-Riahi, H.A.; Polissiou, M.G. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J. Agric. Food Chem., 2007, 55(3), 970-977.
[http://dx.doi.org/10.1021/jf062638l] [PMID: 17263501]
[75]
Ordoudi, S.A.; Befani, C.D.; Nenadis, N.; Koliakos, G.G.; Tsimidou, M.Z. Further examination of antiradical properties of Crocus sativus stigmas extract rich in crocins. J. Agric. Food Chem., 2009, 57(8), 3080-3086.
[http://dx.doi.org/10.1021/jf804041g] [PMID: 19284715]
[76]
Akbar, M.; Essa, M.M.; Daradkeh, G.; Abdelmegeed, M.A.; Choi, Y.; Mahmood, L.; Song, B.J. Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress. Brain Res., 2016, 1637(Suppl. C), 34-55.
[http://dx.doi.org/10.1016/j.brainres.2016.02.016] [PMID: 26883165]
[77]
Kalogeris, T.; Baines, C.P.; Krenz, M.; Korthuis, R.J. Cell biology of ischemia/reperfusion injury. Int. Rev. Cell Mol. Biol., 2012, 298, 229-317.
[http://dx.doi.org/10.1016/B978-0-12-394309-5.00006-7] [PMID: 22878108]
[78]
Karaman, A.; Turkmen, E.; Gursul, C.; Tas, E.; Fadillioglu, E. Prevention of renal ischemia/reperfusion-induced injury in rats by leflunomide. Int. J. Urol., 2006, 13(11), 1434-1441.
[http://dx.doi.org/10.1111/j.1442-2042.2006.01592.x] [PMID: 17083399]
[79]
Betzen, C.; White, R.; Zehendner, C.M.; Pietrowski, E.; Bender, B.; Luhmann, H.J.; Kuhlmann, C.R. Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium. Free Radic. Biol. Med., 2009, 47(8), 1212-1220.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.07.034] [PMID: 19660541]
[80]
Reyes, R.C.; Brennan, A.M.; Shen, Y.; Baldwin, Y.; Swanson, R.A. Activation of neuronal NMDA receptors induces superoxide-mediated oxidative stress in neighboring neurons and astrocytes. J. Neurosci., 2012, 32(37), 12973-12978.
[http://dx.doi.org/10.1523/JNEUROSCI.1597-12.2012] [PMID: 22973021]
[81]
Coyle, J.T.; Puttfarcken, P. Oxidative stress, glutamate, and neurodegenerative disorders. Science, 1993, 262(5134), 689-695.
[http://dx.doi.org/10.1126/science.7901908] [PMID: 7901908]
[82]
Parks, J.K.; Smith, T.S.; Trimmer, P.A.; Bennett, J.P., Jr; Parker, W.D., Jr Neurotoxic Abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J. Neurochem., 2001, 76(4), 1050-1056.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00112.x] [PMID: 11181824]
[83]
Ghadrdoost, B.; Vafaei, A.A.; Rashidy-Pour, A.; Hajisoltani, R.; Bandegi, A.R.; Motamedi, F.; Haghighi, S.; Sameni, H.R.; Pahlvan, S. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur. J. Pharmacol., 2011, 667(1-3), 222-229.
[http://dx.doi.org/10.1016/j.ejphar.2011.05.012] [PMID: 21616066]
[84]
Neumar, R.W. Molecular mechanisms of ischemic neuronal injury. Ann. Emerg. Med., 2000, 36(5), 483-506.
[http://dx.doi.org/10.1016/S0196-0644(00)82028-4] [PMID: 11054204]
[85]
Taoufik, E.; Probert, L. Ischemic neuronal damage. Curr. Pharm. Des., 2008, 14(33), 3565-3573.
[http://dx.doi.org/10.2174/138161208786848748] [PMID: 19075733]
[86]
Ghahghaei, A.; Bathaie, S.Z.; Kheirkhah, H.; Bahraminejad, E. The protective effect of crocin on the amyloid fibril formation of Aβ42 peptide in vitro. Cell. Mol. Biol. Lett., 2013, 18(3), 328-339.
[http://dx.doi.org/10.2478/s11658-013-0092-1] [PMID: 23737042]
[87]
Karakani, A.M.; Riazi, G.; Mahmood Ghaffari, S.; Ahmadian, S.; Mokhtari, F.; Jalili Firuzi, M.; Zahra Bathaie, S. Inhibitory effect of corcin on aggregation of 1N/4R human tau protein in vitro. Iran. J. Basic Med. Sci., 2015, 18(5), 485-492.
[PMID: 26124935]
[88]
Brunden, K.R.; Ballatore, C.; Crowe, A.; Smith, A.B., III
Lee, V.M.; Trojanowski, J.Q. Tau-directed drug discovery for Alzheimer’s disease and related tauopathies: a focus on tau assembly inhibitors. Exp. Neurol., 2010, 223(2), 304-310.
[http://dx.doi.org/10.1016/j.expneurol.2009.08.031] [PMID: 19744482]
[89]
Hensley, K.; Carney, J.M.; Mattson, M.P.; Aksenova, M.; Harris, M.; Wu, J.F.; Floyd, R.A.; Butterfield, D.A. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc. Natl. Acad. Sci. USA, 1994, 91(8), 3270-3274.
[http://dx.doi.org/10.1073/pnas.91.8.3270] [PMID: 8159737]
[90]
Butterfield, D.A.; Swomley, A.M.; Sultana, R. Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid. Redox Signal., 2013, 19(8), 823-835.
[http://dx.doi.org/10.1089/ars.2012.5027] [PMID: 23249141]
[91]
Butterfield, D.A.; Boyd-Kimball, D. The critical role of methionine 35 in Alzheimer’s amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity. Biochim. Biophys. Acta, 2005, 1703(2), 149-156.
[http://dx.doi.org/10.1016/j.bbapap.2004.10.014] [PMID: 15680223]
[92]
Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[93]
Asadi, F.; Jamshidi, A.H.; Khodagholi, F.; Yans, A.; Azimi, L.; Faizi, M.; Vali, L.; Abdollahi, M.; Ghahremani, M.H.; Sharifzadeh, M. Reversal effects of crocin on amyloid beta-induced memory deficit: Modification of autophagy or apoptosis markers. Pharmacol. Biochem. Behav, 2015, 139(Part A), 47-58.
[94]
Varadarajan, S.; Yatin, S.; Aksenova, M.; Butterfield, D.A. Review: Alzheimer’s amyloid beta-peptide-associated free radical oxidative stress and neurotoxicity. J. Struct. Biol., 2000, 130(2-3), 184-208.
[http://dx.doi.org/10.1006/jsbi.2000.4274] [PMID: 10940225]
[95]
Amin, H.; Nieus, T.; Lonardoni, D.; Maccione, A.; Berdondini, L. High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies. Sci. Rep., 2017, 7(1), 2460.
[http://dx.doi.org/10.1038/s41598-017-02635-x] [PMID: 28550283]
[96]
Butterfield, D.A.; Kanski, J. Methionine residue 35 is critical for the oxidative stress and neurotoxic properties of Alzheimer’s amyloid beta-peptide 1-42. Peptides, 2002, 23(7), 1299-1309.
[http://dx.doi.org/10.1016/S0196-9781(02)00066-9] [PMID: 12128086]
[97]
Schöneich, C. Methionine oxidation by reactive oxygen species: reaction mechanisms and relevance to Alzheimer’s disease. Biochim. Biophys. Acta, 2005, 1703(2), 111-119.
[http://dx.doi.org/10.1016/j.bbapap.2004.09.009] [PMID: 15680219]
[98]
Stadtman, E.R.; Van Remmen, H.; Richardson, A.; Wehr, N.B.; Levine, R.L. Methionine oxidation and aging. Biochim. Biophys. Acta, 2005, 1703(2), 135-140.
[http://dx.doi.org/10.1016/j.bbapap.2004.08.010] [PMID: 15680221]
[99]
Wang, X.; Su, B.; Perry, G.; Smith, M.A.; Zhu, X. Insights into amyloid-beta-induced mitochondrial dysfunction in Alzheimer disease. Free Radic. Biol. Med., 2007, 43(12), 1569-1573.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.09.007] [PMID: 18037122]
[100]
Morais, V.A.; De Strooper, B. Mitochondria dysfunction and neurodegenerative disorders: cause or consequence. J. Alzheimers Dis., 2010, 20(Suppl. 2), S255-S263.
[http://dx.doi.org/10.3233/JAD-2010-100345] [PMID: 20463408]
[101]
Pavlov, P.F.; Hansson Petersen, C.; Glaser, E.; Ankarcrona, M. Mitochondrial accumulation of APP and Abeta: significance for Alzheimer disease pathogenesis. J. Cell. Mol. Med., 2009, 13(10), 4137-4145.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00892.x] [PMID: 19725915]
[102]
Pagani, L.; Eckert, A. Amyloid-Beta interaction with mitochondria. Int. J. Alzheimers Dis., 2011, 2011, 925050.
[http://dx.doi.org/10.4061/2011/925050] [PMID: 21461357]
[103]
Deslauriers, A.M.; Afkhami-Goli, A.; Paul, A.M.; Bhat, R.K.; Acharjee, S.; Ellestad, K.K.; Noorbakhsh, F.; Michalak, M.; Power, C. Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. J. Immunol., 2011, 187(9), 4788-4799.
[http://dx.doi.org/10.4049/jimmunol.1004111] [PMID: 21964030]
[104]
Moreira, P.I.; Santos, M.S.; Oliveira, C.R. Alzheimer’s disease: a lesson from mitochondrial dysfunction. Antioxid. Redox Signal., 2007, 9(10), 1621-1630.
[http://dx.doi.org/10.1089/ars.2007.1703] [PMID: 17678440]
[105]
Grieb, P. Intracerebroventricular streptozotocin injections as a model of alzheimer’s disease: In search of a relevant mechanism. Mol. Neurobiol., 2016, 53(3), 1741-1752.
[http://dx.doi.org/10.1007/s12035-015-9132-3] [PMID: 25744568]
[106]
Parks, J.K.; Smith, T.S.; Trimmer, P.A.; Bennett, J.P., Jr; Parker, W.D. Jr Neurotoxic Abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J. Neurochem., 2001, 76(4), 1050-1056.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00112.x] [PMID: 11181824]
[107]
Friedland-Leuner, K.; Stockburger, C.; Denzer, I.; Eckert, G.P.; Müller, W.E. Mitochondrial dysfunction: cause and consequence of Alzheimer’s disease. Prog. Mol. Biol. Transl. Sci., 2014, 127, 183-210.
[http://dx.doi.org/10.1016/B978-0-12-394625-6.00007-6] [PMID: 25149218]
[108]
Yabu, T.; Shiba, H.; Shibasaki, Y.; Nakanishi, T.; Imamura, S.; Touhata, K.; Yamashita, M. Stress-induced ceramide generation and apoptosis via the phosphorylation and activation of nSMase1 by JNK signaling. Cell Death Differ., 2015, 22(2), 258-273.
[http://dx.doi.org/10.1038/cdd.2014.128] [PMID: 25168245]
[109]
Chen, C.L.; Lin, C.F.; Chang, W.T.; Huang, W.C.; Teng, C.F.; Lin, Y.S. Ceramide induces p38 MAPK and JNK activation through a mechanism involving a thioredoxin-interacting protein-mediated pathway. Blood, 2008, 111(8), 4365-4374.
[http://dx.doi.org/10.1182/blood-2007-08-106336] [PMID: 18270325]
[110]
Giraldo, E.; Lloret, A.; Fuchsberger, T.; Viña, J. Aβ and tau toxicities in Alzheimer’s are linked via oxidative stress-induced p38 activation: protective role of vitamin E. Redox Biol., 2014, 2(Suppl. C), 873-877.
[http://dx.doi.org/10.1016/j.redox.2014.03.002] [PMID: 25061569]
[111]
Lloret, A.; Fuchsberger, T.; Giraldo, E.; Viña, J. Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease. Free Radic. Biol. Med., 2015, 83(Suppl. C), 186-191.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.028] [PMID: 25746773]
[112]
Eckert, A.; Schulz, K.L.; Rhein, V.; Götz, J. Convergence of amyloid-beta and tau pathologies on mitochondria in vivo. Mol. Neurobiol., 2010, 41(2-3), 107-114.
[http://dx.doi.org/10.1007/s12035-010-8109-5] [PMID: 20217279]
[113]
Geromichalos, G.D.; Lamari, F.N.; Papandreou, M.A.; Trafalis, D.T.; Margarity, M.; Papageorgiou, A.; Sinakos, Z. Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies. J. Agric. Food Chem., 2012, 60(24), 6131-6138.
[http://dx.doi.org/10.1021/jf300589c] [PMID: 22655699]
[114]
Kang, S.W.; Kim, S.J.; Kim, M.S. Oxidative stress with tau hyperphosphorylation in memory impaired 1,2-diacetylbenzene-treated mice. Toxicol. Lett., 2017, 279, 53-59.
[http://dx.doi.org/10.1016/j.toxlet.2017.07.892] [PMID: 28734998]
[115]
Kozlov, S.; Afonin, A.; Evsyukov, I.; Bondarenko, A. Alzheimer’s disease: as it was in the beginning. Rev. Neurosci., 2017, 28(8), 825-843.
[http://dx.doi.org/10.1515/revneuro-2017-0006] [PMID: 28704198]
[116]
Luo, J.; Shi, R. Acrolein induces oxidative stress in brain mitochondria. Neurochem. Int., 2005, 46(3), 243-252.
[http://dx.doi.org/10.1016/j.neuint.2004.09.001] [PMID: 15670641]
[117]
Morelli, S.; Salerno, S.; Piscioneri, A.; Tasselli, F.; Drioli, E.; De Bartolo, L. Neuronal membrane bioreactor as a tool for testing crocin neuroprotective effect in Alzheimer’s disease. Chem. Eng. J., 2016, 305(Suppl. C), 69-78.
[http://dx.doi.org/10.1016/j.cej.2016.01.035]
[118]
Ghahghaei, A.; Bathaie, S.Z.; Bahraminejad, E. Mechanisms of the effects of crocin on aggregation and deposition of Aβ1–40 fibrils in alzheimer’s disease. Int. J. Pept. Res. Ther., 2012, 18(4), 347-351.
[http://dx.doi.org/10.1007/s10989-012-9308-x]
[119]
Ahn, J.H.; Hu, Y.; Hernandez, M.; Kim, J.R. Crocetin inhibits beta-amyloid fibrillization and stabilizes beta-amyloid oligomers. Biochem. Biophys. Res. Commun., 2011, 414(1), 79-83.
[http://dx.doi.org/10.1016/j.bbrc.2011.09.025] [PMID: 21945434]
[120]
Yoshino, Y.; Ishisaka, M.; Umigai, N.; Shimazawa, M.; Tsuruma, K.; Hara, H. Crocetin prevents amyloid β1-42-induced cell death in murine hippocampal cells. Pharmacol. Pharm., 2014, 05(01), 37-42.
[http://dx.doi.org/10.4236/pp.2014.51007]
[121]
Tiribuzi, R.; Crispoltoni, L.; Chiurchiù, V.; Casella, A.; Montecchiani, C.; Del Pino, A.M.; Maccarrone, M.; Palmerini, C.A.; Caltagirone, C.; Kawarai, T.; Orlacchio, A.; Orlacchio, A. Trans-crocetin improves amyloid-β degradation in monocytes from Alzheimer’s Disease patients. J. Neurol. Sci., 2017, 372(Suppl. C), 408-412.
[http://dx.doi.org/10.1016/j.jns.2016.11.004] [PMID: 27865556]
[122]
Zarei Jaliani, H.; Riazi, G.H.; Ghaffari, S.M.; Karima, O.; Rahmani, A. The effect of the crocus sativus L. Carotenoid, crocin, on the polymerization of microtubules, in vitro. Iran. J. Basic Med. Sci., 2013, 16(1), 101-107.
[PMID: 23638298]
[123]
Hire, R.R.; Srivastava, S.; Davis, M.B.; Kumar Konreddy, A.; Panda, D. Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells. Sci. Rep., 2017, 7, 44984.
[http://dx.doi.org/10.1038/srep44984] [PMID: 28337976]
[124]
Rao, S.V. Muralidhara; Yenisetti, S.C.; Rajini, P.S. Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism. Neurotoxicology, 2016, 52, 230-242.
[http://dx.doi.org/10.1016/j.neuro.2015.12.010] [PMID: 26705857]
[125]
Georgiadou, G.; Grivas, V.; Tarantilis, P.A.; Pitsikas, N. Crocins, the active constituents of Crocus Sativus L., counteracted ketamine-induced behavioural deficits in rats. Psychopharmacology (Berl.), 2014, 231(4), 717-726.
[http://dx.doi.org/10.1007/s00213-013-3293-4] [PMID: 24096536]
[126]
Pitsikas, N. The Effect of Crocus sativus L. and Its Constituents on Memory: Basic Studies and Clinical Applications. Evid. Based Complement. Alternat. Med., 2015, 2015, 926284.
[http://dx.doi.org/10.1155/2015/926284] [PMID: 25713594]
[127]
Zhang, Y.; Shoyama, Y.; Sugiura, M.; Saito, H. Effects of Crocus sativus L. on the ethanol-induced impairment of passive avoidance performances in mice. Biol. Pharm. Bull., 1994, 17(2), 217-221.
[http://dx.doi.org/10.1248/bpb.17.217] [PMID: 8205119]
[128]
Abe, K.; Sugiura, M.; Shoyama, Y.; Saito, H. Crocin antagonizes ethanol inhibition of NMDA receptor-mediated responses in rat hippocampal neurons. Brain Res., 1998, 787(1), 132-138.
[http://dx.doi.org/10.1016/S0006-8993(97)01505-9] [PMID: 9518580]
[129]
Subramaniam, S.R.; Chesselet, M.F. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog. Neurobiol, 2013, 106-107(Suppl C), 17-32.
[http://dx.doi.org/10.1016/j.pneurobio.2013.04.004]] [PMID: 23643800]
[130]
Pitsikas, N.; Zisopoulou, S.; Tarantilis, P.A.; Kanakis, C.D.; Polissiou, M.G.; Sakellaridis, N. Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats’ memory. Behav. Brain Res., 2007, 183(2), 141-146.
[http://dx.doi.org/10.1016/j.bbr.2007.06.001] [PMID: 17628713]
[131]
Bandegi, A.R.; Rashidy-Pour, A.; Vafaei, A.A.; Ghadrdoost, B. Protective Effects of Crocus Sativus L. Extract and Crocin against Chronic-Stress Induced Oxidative Damage of Brain, Liver and Kidneys in Rats. Adv. Pharm. Bull., 2014, 4(Suppl. 2), 493-499.
[PMID: 25671180]
[132]
Naghizadeh, B.; Mansouri, S.M.; Mashhadian, N.V. Crocin attenuates cisplatin-induced renal oxidative stress in rats. Food Chem. Toxicol., 2010, 48(10), 2650-2655.
[http://dx.doi.org/10.1016/j.fct.2010.06.035] [PMID: 20600529]
[133]
Naghizadeh, B.; Boroushaki, M.T.; Vahdati Mashhadian, N.; Mansouri, M.T. Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. Iran. Biomed. J., 2008, 12(2), 93-100.
[PMID: 18506215]
[134]
Naghizadeh, B.; Mansouri, M.T.; Ghorbanzadeh, B. Protective effects of crocin against streptozotocin-induced oxidative damage in rat striatum. Acta Med. Iran., 2014, 52(2), 101-105.
[PMID: 24659065]
[135]
Naghizadeh, B.; Mansouri, M.T.; Ghorbanzadeh, B.; Farbood, Y.; Sarkaki, A. Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats. Phytomedicine, 2013, 20(6), 537-542.
[http://dx.doi.org/10.1016/j.phymed.2012.12.019] [PMID: 23351962]
[136]
Labak, M.; Foniok, T.; Kirk, D.; Rushforth, D.; Tomanek, B.; Jasiński, A.; Grieb, P. Metabolic changes in rat brain following intracerebroventricular injections of streptozotocin: a model of sporadic Alzheimer’s disease. Acta Neurochir. Suppl. (Wien), 2010, 106, 177-181.
[http://dx.doi.org/10.1007/978-3-211-98811-4_32] [PMID: 19812944]
[137]
Khalili, M.; Hamzeh, F. Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer’s disease in male rats. Iran. Biomed. J., 2010, 14(1-2), 59-65.
[PMID: 20683499]
[138]
Moghe, A.; Ghare, S.; Lamoreau, B.; Mohammad, M.; Barve, S.; McClain, C.; Joshi-Barve, S. Molecular mechanisms of acrolein toxicity: relevance to human disease. Toxicol. Sci., 2015, 143(2), 242-255.
[http://dx.doi.org/10.1093/toxsci/kfu233] [PMID: 25628402]
[139]
Jia, L.; Liu, Z.; Sun, L.; Miller, S.S.; Ames, B.N.; Cotman, C.W.; Liu, J. Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid. Invest. Ophthalmol. Vis. Sci., 2007, 48(1), 339-348.
[http://dx.doi.org/10.1167/iovs.06-0248] [PMID: 17197552]
[140]
Hamann, K.; Shi, R. Acrolein scavenging: a potential novel mechanism of attenuating oxidative stress following spinal cord injury. J. Neurochem., 2009, 111(6), 1348-1356.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06395.x] [PMID: 19780896]
[141]
Stevens, J.F.; Maier, C.S. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol. Nutr. Food Res., 2008, 52(1), 7-25.
[http://dx.doi.org/10.1002/mnfr.200700412] [PMID: 18203133]
[142]
Rashedinia, M.; Lari, P.; Abnous, K.; Hosseinzadeh, H. Protective effect of crocin on acrolein-induced tau phosphorylation in the rat brain. Acta Neurobiol. Exp. (Warsz.), 2015, 75(2), 208-219.
[PMID: 26232997]
[143]
Ochiai, T.; Ohno, S.; Soeda, S.; Tanaka, H.; Shoyama, Y.; Shimeno, H. Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of alpha-tocopherol. Neurosci. Lett., 2004, 362(1), 61-64.
[http://dx.doi.org/10.1016/j.neulet.2004.02.067] [PMID: 15147781]
[144]
Ochiai, T.; Shimeno, H.; Mishima, K.; Iwasaki, K.; Fujiwara, M.; Tanaka, H.; Shoyama, Y.; Toda, A.; Eyanagi, R.; Soeda, S. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochim. Biophys. Acta, 2007, 1770(4), 578-584.
[http://dx.doi.org/10.1016/j.bbagen.2006.11.012] [PMID: 17215084]
[145]
Soeda, S.; Aritake, K.; Urade, Y.; Sato, H.; Shoyama, Y. Neuroprotective activities of saffron and crocin. Adv. Neurobiol., 2016, 12, 275-292.
[http://dx.doi.org/10.1007/978-3-319-28383-8_14] [PMID: 27651258]
[146]
Soeda, S.; Ochiai, T.; Paopong, L.; Tanaka, H.; Shoyama, Y.; Shimeno, H. Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells. Life Sci., 2001, 69(24), 2887-2898.
[http://dx.doi.org/10.1016/S0024-3205(01)01357-1] [PMID: 11720092]
[147]
Akhondzadeh, S.; Shafiee Sabet, M.; Harirchian, M.H.; Togha, M.; Cheraghmakani, H.; Razeghi, S.; Hejazi, S.S.; Yousefi, M.H.; Alimardani, R.; Jamshidi, A.; Rezazadeh, S.A.; Yousefi, A.; Zare, F.; Moradi, A.; Vossoughi, A. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl.), 2010, 207(4), 637-643.
[http://dx.doi.org/10.1007/s00213-009-1706-1] [PMID: 19838862]
[148]
Akhondzadeh, S.; Sabet, M.S.; Harirchian, M.H.; Togha, M.; Cheraghmakani, H.; Razeghi, S.; Hejazi, S.Sh.; Yousefi, M.H.; Alimardani, R.; Jamshidi, A.; Zare, F.; Moradi, A. Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16-week, randomized and placebo-controlled trial. J. Clin. Pharm. Ther., 2010, 35(5), 581-588.
[http://dx.doi.org/10.1111/j.1365-2710.2009.01133.x] [PMID: 20831681]
[149]
Tsolaki, M.; Karathanasi, E.; Lazarou, I.; Dovas, K.; Verykouki, E.; Karacostas, A.; Georgiadis, K.; Tsolaki, A.; Adam, K.; Kompatsiaris, I.; Sinakos, Z. Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial. J. Alzheimers Dis., 2016, 54(1), 129-133.
[http://dx.doi.org/10.3233/JAD-160304] [PMID: 27472878]
[150]
Farokhnia, M.; Shafiee Sabet, M.; Iranpour, N.; Gougol, A.; Yekehtaz, H.; Alimardani, R.; Farsad, F.; Kamalipour, M.; Akhondzadeh, S. Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer’s disease: a double-blind randomized clinical trial. Hum. Psychopharmacol., 2014, 29(4), 351-359.
[http://dx.doi.org/10.1002/hup.2412] [PMID: 25163440]
[151]
Talaei, A.; Hassanpour, M.M.; Sajadi, T.S.A.; Mohajeri, S.A. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: a randomized, double-blind, placebo-controlled, pilot clinical trial. J. Affect. Disord., 2015, 174(Suppl. C), 51-56.
[http://dx.doi.org/10.1016/j.jad.2014.11.035] [PMID: 25484177]
[152]
Shahmansouri, N.; Farokhnia, M.; Abbasi, S.H.; Kassaian, S.E.; Noorbala Tafti, A.A.; Gougol, A.; Yekehtaz, H.; Forghani, S.; Mahmoodian, M.; Saroukhani, S.; Arjmandi-Beglar, A.; Akhondzadeh, S. A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J. Affect. Disord., 2014, 155(Suppl. C), 216-222.
[http://dx.doi.org/10.1016/j.jad.2013.11.003] [PMID: 24289892]
[153]
Hwang, O. Role of oxidative stress in Parkinson’s disease. Exp. Neurobiol., 2013, 22(1), 11-17.
[http://dx.doi.org/10.5607/en.2013.22.1.11] [PMID: 23585717]
[154]
Blesa, J.; Trigo-Damas, I.; Quiroga-Varela, A.; Jackson-Lewis, V.R. Oxidative stress and Parkinson’s disease. Front. Neuroanat., 2015, 9, 91.
[http://dx.doi.org/10.3389/fnana.2015.00091] [PMID: 26217195]
[155]
Zhou, C.; Huang, Y.; Przedborski, S. Oxidative stress in Parkinson’s disease: a mechanism of pathogenic and therapeutic significance. Ann. N. Y. Acad. Sci., 2008, 1147, 93-104.
[http://dx.doi.org/10.1196/annals.1427.023] [PMID: 19076434]
[156]
Manoharan, S.; Guillemin, G.J.; Abiramasundari, R.S.; Essa, M.M.; Akbar, M.; Akbar, M.D. The role of reactive oxygen species in the pathogenesis of alzheimer’s disease, parkinson’s disease, and huntington’s disease: A mini review. Oxid. Med. Cell. Longev., 2016, 2016, 8590578.
[http://dx.doi.org/10.1155/2016/8590578] [PMID: 28116038]
[157]
Johri, A.; Beal, M.F. Mitochondrial dysfunction in neurodegenerative diseases. J. Pharmacol. Exp. Ther., 2012, 342(3), 619-630.
[http://dx.doi.org/10.1124/jpet.112.192138] [PMID: 22700435]
[158]
Mhyre, T.R.; Boyd, J.T.; Hamill, R.W.; Maguire-Zeiss, K.A. Parkinson’s Disease. Protein Aggregation and Fibrillogenesis in Cerebral and Systemic Amyloid Disease., 2012, 389-455.
[http://dx.doi.org/10.1007/978-94-007-5416-4_16]
[159]
Islam, M.T. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol. Res., 2017, 39(1), 73-82.
[http://dx.doi.org/10.1080/01616412.2016.1251711] [PMID: 27809706]
[160]
Pimentel, C.; Batista-Nascimento, L.; Rodrigues-Pousada, C.; Menezes, R.A. Oxidative stress in Alzheimer’s and Parkinson’s diseases: insights from the yeast Saccharomyces cerevisiae. Oxid. Med. Cell. Longev., 2012, 2012, 132146.
[http://dx.doi.org/10.1155/2012/132146] [PMID: 22701754]
[161]
Anderson, G.; Maes, M. Neurodegeneration in Parkinson’s disease: interactions of oxidative stress, tryptophan catabolites and depression with mitochondria and sirtuins. Mol. Neurobiol., 2014, 49(2), 771-783.
[http://dx.doi.org/10.1007/s12035-013-8554-z] [PMID: 24085563]
[162]
Chen, C.H.; Ferreira, J.C.; Gross, E.R.; Mochly-Rosen, D. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol. Rev., 2014, 94(1), 1-34.
[http://dx.doi.org/10.1152/physrev.00017.2013] [PMID: 24382882]
[163]
Rajaei, Z.; Hosseini, M.; Alaei, H. Effects of crocin on brain oxidative damage and aversive memory in a 6-OHDA model of Parkinson’s disease. Arq. Neuropsiquiatr., 2016, 74(9), 723-729.
[http://dx.doi.org/10.1590/0004-282X20160131] [PMID: 27706421]
[164]
Ahmad, A.S.; Ansari, M.A.; Ahmad, M.; Saleem, S.; Yousuf, S.; Hoda, M.N.; Islam, F. Neuroprotection by crocetin in a hemi-parkinsonian rat model. Pharmacol. Biochem. Behav., 2005, 81(4), 805-813.
[http://dx.doi.org/10.1016/j.pbb.2005.06.007] [PMID: 16005057]
[165]
Tanner, C.M.; Kamel, F.; Ross, G.W.; Hoppin, J.A.; Goldman, S.M.; Korell, M.; Marras, C.; Bhudhikanok, G.S.; Kasten, M.; Chade, A.R.; Comyns, K.; Richards, M.B.; Meng, C.; Priestley, B.; Fernandez, H.H.; Cambi, F.; Umbach, D.M.; Blair, A.; Sandler, D.P.; Langston, J.W. Rotenone, paraquat, and Parkinson’s disease. Environ. Health Perspect., 2011, 119(6), 866-872.
[http://dx.doi.org/10.1289/ehp.1002839] [PMID: 21269927]
[166]
Pan, P.K.; Qiao, L.Y.; Wen, X.N. Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson’s disease through regulating Keap1/Nrf2 signaling pathway. Cell. Mol. Biol., 2016, 62(14), 11-17.
[http://dx.doi.org/10.14715/cmb/2016.62.14.2] [PMID: 28145852]
[167]
Prediger, R.D.; Aguiar, A.S., Jr; Moreira, E.L.; Matheus, F.C.; Castro, A.A.; Walz, R.; De Bem, A.F.; Latini, A.; Tasca, C.I.; Farina, M.; Raisman-Vozari, R. The intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a new rodent model to test palliative and neuroprotective agents for Parkinson’s disease. Curr. Pharm. Des., 2011, 17(5), 489-507.
[http://dx.doi.org/10.2174/138161211795164095] [PMID: 21375482]
[168]
Schmidt, N.; Ferger, B. Neurochemical findings in the MPTP model of Parkinson’s disease. J. Neural Transm. (Vienna), 2001, 108(11), 1263-1282.
[http://dx.doi.org/10.1007/s007020100004] [PMID: 11768626]
[169]
Purushothuman, S.; Nandasena, C.; Peoples, C.L.; El Massri, N.; Johnstone, D.M.; Mitrofanis, J.; Stone, J. Saffron pre-treatment offers neuroprotection to Nigral and retinal dopaminergic cells of MPTP-Treated mice. J. Parkinsons Dis., 2013, 3(1), 77-83.
[PMID: 23938314]
[170]
Zhang, G.F.; Zhang, Y.; Zhao, G. Crocin protects PC12 cells against MPP(+)-induced injury through inhibition of mitochondrial dysfunction and ER stress. Neurochem. Int., 2015, 89(Suppl. C), 101-110.
[http://dx.doi.org/10.1016/j.neuint.2015.07.011] [PMID: 26209153]
[171]
Bitanihirwe, B.K.; Woo, T.U. Oxidative stress in schizophrenia: an integrated approach. Neurosci. Biobehav. Rev., 2011, 35(3), 878-893.
[http://dx.doi.org/10.1016/j.neubiorev.2010.10.008] [PMID: 20974172]
[172]
Reddy, R.D.; Yao, J.K. Free radical pathology in schizophrenia: a review. Prostaglandins Leukot. Essent. Fatty Acids, 1996, 55(1-2), 33-43.
[http://dx.doi.org/10.1016/S0952-3278(96)90143-X] [PMID: 8888121]
[173]
Yao, J.K.; Leonard, S.; Reddy, R. Altered glutathione redox state in schizophrenia. Dis. Markers, 2006, 22(1-2), 83-93.
[http://dx.doi.org/10.1155/2006/248387] [PMID: 16410648]
[174]
Gawryluk, J.W.; Wang, J.F.; Andreazza, A.C.; Shao, L.; Young, L.T. Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int. J. Neuropsychopharmacol., 2011, 14(1), 123-130.
[http://dx.doi.org/10.1017/S1461145710000805] [PMID: 20633320]
[175]
Zhang, X.Y.; Chen, D.C.; Xiu, M.H.; Wang, F.; Qi, L.Y.; Sun, H.Q.; Chen, S.; He, S.C.; Wu, G.Y.; Haile, C.N.; Kosten, T.A.; Lu, L.; Kosten, T.R. The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients. Schizophr. Res., 2009, 113(2-3), 151-157.
[http://dx.doi.org/10.1016/j.schres.2009.05.016] [PMID: 19540723]
[176]
Mousavi, B.; Bathaie, S.Z.; Fadai, F.; Ashtari, Z.; Ali Beigi, N.; Farhang, S.; Hashempour, S.; Shahhamzei, N.; Heidarzadeh, H. Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia. Avicenna J. Phytomed., 2015, 5(5), 413-419.
[PMID: 26468460]
[177]
Fadai, F.; Mousavi, B.; Ashtari, Z. Ali beigi, N.; Farhang, S.; Hashempour, S.; Shahhamzei, N.; Bathaie, S.Z. Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: a randomized triple blind placebo controlled study. Pharmacopsychiatry, 2014, 47(4-5), 156-161.
[PMID: 24955550]


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VOLUME: 17
ISSUE: 4
Year: 2019
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DOI: 10.2174/1570159X16666180321095705
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