{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:12:56Z","timestamp":1793833976781,"version":"4.6.1"},"reference-count":117,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    Saffron (\n                    <jats:italic toggle=\"yes\">Crocus sativus<\/jats:italic>\n                    L.) has been traditionally used in food preparation and as a medicinal plant. It currently has numerous therapeutic properties attributed to it, such as protection against ischemia, as well as anticonvulsant, antidepressant, anxiolytic, hypolipidemic, anti-atherogenic, anti-hypertensive, antidiabetic, and anti-cancer properties. In addition, saffron has remarkable beneficial properties, such as anti-apoptotic, anti-inflammatory and antioxidant activities, due to its main metabolites, among which crocin and crocetin stand out. Furthermore, increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases, such as Parkinson\u2019s and Alzheimer\u2019s diseases, both in experimental models and in clinical studies in patients. Currently, saffron supplementation is being tested for ocular neurodegenerative pathologies, such as diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration and glaucoma, among others, and shows beneficial effects. The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases. This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.4103\/1673-5374.274325","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T08:20:21Z","timestamp":1580199621000},"page":"1408-1416","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":62,"title":["Beneficial effects of saffron (Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases"],"prefix":"10.4103","volume":"15","author":[{"given":"Jose A.","family":"Fern\u00e1ndez-Albarral","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Oftalmol\u00f3gicas Ram\u00f3n Castroviejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"de Hoz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Oftalmol\u00f3gicas Ram\u00f3n Castroviejo, Madrid, Spain"},{"name":"Departamento de Inmunolog\u00eda, Oftalmolog\u00eda y ORL, Facultad de \u00d3ptica y Optometr\u00eda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Oftalmol\u00f3gicas Ram\u00f3n Castroviejo, Madrid, Spain"},{"name":"Departamento de Inmunolog\u00eda, Oftalmolog\u00eda y ORL, Facultad de \u00d3ptica y Optometr\u00eda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"L\u00f3pez-Cuenca","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Oftalmol\u00f3gicas Ram\u00f3n Castroviejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Salobrar-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Oftalmol\u00f3gicas Ram\u00f3n Castroviejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda D.","family":"Pinazo-Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Oftalmol\u00f3gica Santiago Grisolia, Universidad de Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5145-5094","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Oftalmol\u00f3gicas Ram\u00f3n Castroviejo, Madrid, Spain"},{"name":"Departamento de Inmunolog\u00eda, Oftalmolog\u00eda y ORL, Facultad de Medicina, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5480-5902","authenticated-orcid":false,"given":"Juan J.","family":"Salazar","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Oftalmol\u00f3gicas Ram\u00f3n Castroviejo, Madrid, Spain"},{"name":"Departamento de Inmunolog\u00eda, Oftalmolog\u00eda y ORL, Facultad de \u00d3ptica y Optometr\u00eda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,8]]},"reference":[{"key":"R1-20260525","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.pbb.2005.06.007","article-title":"Neuroprotection by crocetin in a hemi-parkinsonian rat model","volume":"81","author":"Ahmad","year":"2005","journal-title":"Pharmacol Biochem Behav"},{"key":"R2-20260525","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1365-2710.2009.01133.x","article-title":"Saffron in the treatment of patients with mild to moderate Alzheimer\u2019s disease: a 16-week randomized and placebo-controlled trial","volume":"35","author":"Akhondzadeh","year":"2010","journal-title":"J Clin Pharm Ther"},{"key":"R3-20260525","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijgfs.2018.03.001","article-title":"affron\u00aeeye a natural extract of saffron (Crocus sativus L) with colorant properties as novel replacer of saffron stigmas in culinary and food applications","volume":"12","author":"Almod\u00f3var","year":"2018","journal-title":"Int J Gastron Food Sci"},{"key":"R4-20260525","doi-asserted-by":"crossref","first-page":"7302","DOI":"10.1021\/jf0509355","article-title":"Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice","volume":"53","author":"Asai","year":"2005","journal-title":"J Agric Food Chem"},{"key":"R5-20260525","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1002\/ptr.1749","article-title":"Radical scavenging activity of Crocus sativus L extract and its bioactive constituents","volume":"19","author":"Assimopoulou","year":"2005","journal-title":"Phytother Res"},{"key":"R6-20260525","first-page":"13","article-title":"Safranal, an active ingredient of saffron, attenuates cognitive deficits in amyloid \u03b2-induced rat model of Alzheimer\u2019s disease: underlying mechanisms","volume":"1","author":"Baluchnejadmojarad","year":"2019","journal-title":"Metab Brain Dis"},{"key":"R7-20260525","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0278-5846(03)00023-X","article-title":"A new view of diabetic retinopathy: a neurodegenerative disease of the eye","volume":"27","author":"Barber","year":"2003","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"R8-20260525","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/BF02858789","article-title":"Uses of saffron","volume":"37","author":"Basker","year":"1983","journal-title":"Econ Bot"},{"key":"R9-20260525","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3109\/10520295.2014.890741","article-title":"A review of the chemistry and uses of crocins and crocetin, the carotenoid natural dyes in saffron, with particular emphasis on applications as colorants including their use as biological stains","volume":"89","author":"Bathaie","year":"2014","journal-title":"Biotech Histochem"},{"key":"R10-20260525","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration","volume":"45","author":"Beatty","year":"2000","journal-title":"Surv Ophthalmol"},{"key":"R11-20260525","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1017\/S0952523814000108","article-title":"Saffron and retina: neuroprotection and pharmacokinetics","volume":"31","author":"Bisti","year":"2014","journal-title":"Vis Neurosci"},{"key":"R12-20260525","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1186\/1472-6882-14-399","article-title":"The ocular hypotensive effect of saffron extract in primary open angle glaucoma: A pilot study","volume":"14","author":"Bonyadi","year":"2014","journal-title":"BMC Complement Altern Med"},{"key":"R13-20260525","doi-asserted-by":"crossref","first-page":"300","DOI":"10.31083\/ph.2010.9760","article-title":"Inhibitory effect of Crocus sativus (saffron) on histamine (H1) receptors of guinea pig tracheal chains","volume":"65","author":"Boskabady","year":"2010","journal-title":"Pharmazie"},{"key":"R14-20260525","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00417-018-4163-x","article-title":"Saffron therapy for the treatment of mild\/moderate age-related macular degeneration: a randomised clinical trial","volume":"257","author":"Broadhead","year":"2019","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"R15-20260525","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.brainres.2015.08.031","article-title":"How microglia kill neurons","volume":"1628","author":"Brown","year":"2015","journal-title":"Brain Res"},{"key":"R16-20260525","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.biopha.2017.12.090","article-title":"A comprehensive review of the pharmacological potential of Crocus sativus and its bioactive apocarotenoids","volume":"98","author":"Bukhari","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"R17-20260525","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.pneurobio.2011.05.011","article-title":"Age related macular degeneration and drusen: Neuroinflammation in the retina","volume":"95","author":"Buschini","year":"2011","journal-title":"Prog Neurobiol"},{"key":"R18-20260525","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s12035-012-8391-5","article-title":"The ubiquitin-proteasome system in retinal health and disease","volume":"47","author":"Campello","year":"2013","journal-title":"Mol Neurobiol"},{"key":"R19-20260525","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000439026","article-title":"Neuroprotective effects of crocin against oxidative stress induced by ischemia\/reperfusion injury in rat retina","volume":"54","author":"Chen","year":"2015","journal-title":"Ophthalmic Res"},{"key":"R20-20260525","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/jphp.13055","article-title":"Preparation, chemical characterization and determination of crocetin\u2019s pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L) aqueous extract to C57\/BL 6J mice","volume":"71","author":"Christodoulou","year":"2019","journal-title":"J Pharm Pharmacol"},{"key":"R21-20260525","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1111\/jphp.12456","article-title":"Saffron: A natural product with potential pharmaceutical applications","volume":"67","author":"Christodoulou","year":"2015","journal-title":"J Pharm Pharmacol"},{"key":"R22-20260525","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.coph.2012.09.008","article-title":"Oxidative stress and mitochondrial dysfunction in glaucoma","volume":"13","author":"Chrysostomou","year":"2013","journal-title":"Curr Opin Pharmacol"},{"key":"R23-20260525","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11302-015-9490-3","article-title":"Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors","volume":"12","author":"Corso","year":"2016","journal-title":"Purinergic Signal"},{"key":"R24-20260525","doi-asserted-by":"crossref","first-page":"e83733","DOI":"10.1371\/journal.pone.0083733","article-title":"Rod-like microglia are restricted to eyes with laser-induced ocular hypertension but absent from the microglial changes in the contralateral untreated eye","volume":"8","author":"De Hoz","year":"2013","journal-title":"PLoS One"},{"key":"R25-20260525","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.exer.2018.03.006","article-title":"Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension","volume":"171","author":"de Hoz","year":"2018","journal-title":"Exp Eye Res"},{"key":"R26-20260525","doi-asserted-by":"crossref","first-page":"e22292","DOI":"10.1002\/jbt.22292","article-title":"Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma","volume":"33","author":"Deng","year":"2019","journal-title":"J Biochem Mol Toxicol"},{"key":"R27-20260525","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3390\/antiox8070224","article-title":"Saffron: a multitask neuroprotective agent for retinal degenerative diseases","volume":"8","author":"Di Marco","year":"2019","journal-title":"Antioxidants"},{"key":"R28-20260525","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.jdiacomp.2015.12.018","article-title":"Diabetes mellitus: The linkage between oxidative stress inflammation hypercoagulability and vascular complications","volume":"30","author":"Domingueti","year":"2016","journal-title":"J Diabetes Complications"},{"key":"R29-20260525","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/343364a0","article-title":"A point mutation of the rhodopsin gene in one form of retinitis pigmentosa","volume":"343","author":"Dryja","year":"1990","journal-title":"Nature"},{"key":"R30-20260525","doi-asserted-by":"crossref","first-page":"6118","DOI":"10.1167\/iovs.09-4995","article-title":"Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration","volume":"51","author":"Falsini","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R31-20260525","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s10522-012-9409-0","article-title":"Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver","volume":"14","author":"Farahmand","year":"2013","journal-title":"Biogerontology"},{"key":"R32-20260525","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.3390\/ijms20174110","article-title":"Neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract in a model of glaucoma","volume":"20","author":"Fern\u00e1ndez-Albarral","year":"2019","journal-title":"Int J Mol Sci"},{"key":"R33-20260525","doi-asserted-by":"crossref","first-page":"e43074","DOI":"10.1371\/journal.pone.0043074","article-title":"Safranal a saffron constituent attenuates retinal degeneration in P23H rats","volume":"7","author":"Fern\u00e1ndez-S\u00e1nchez","year":"2012","journal-title":"PLoS One"},{"key":"R34-20260525","doi-asserted-by":"crossref","first-page":"13875","DOI":"10.3390\/molecules200813875","article-title":"Natural compounds from saffron and bear bile prevent vision loss and retinal degeneration","volume":"20","author":"Fern\u00e1ndez-S\u00e1nchez","year":"2015","journal-title":"Molecules"},{"key":"R35-20260525","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/1742-2094-9-92","article-title":"IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice retina contralateral to experimental glaucoma","volume":"9","author":"Gallego","year":"2012","journal-title":"J Neuroinflammation"},{"key":"R36-20260525","first-page":"427","article-title":"Glutamate and Alzheimer\u2019s disease","volume":"42","author":"Gazulla","year":"2006","journal-title":"Rev Neurol"},{"key":"R37-20260525","doi-asserted-by":"crossref","first-page":"6131","DOI":"10.1021\/jf300589c","article-title":"Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies","volume":"60","author":"Geromichalos","year":"2012","journal-title":"J Agric Food Chem"},{"key":"R38-20260525","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.biopha.2018.10.031","article-title":"Saffron; An updated review on biological properties with special focus on cardiovascular effects","volume":"109","author":"Ghaffari","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"R39-20260525","doi-asserted-by":"crossref","first-page":"S36","DOI":"10.1097\/IJG.0b013e3182934af6","article-title":"Alzheimer\u2019s disease and glaucoma: mechanistic similarities and differences","volume":"22","author":"Ghiso","year":"2013","journal-title":"J Glaucoma"},{"key":"R40-20260525","doi-asserted-by":"crossref","first-page":"304","DOI":"10.33588\/rn.4806.2008512","article-title":"Mechanisms of secondary degeneration in the central nervous system during acute neural disorders and white matter damage","volume":"48","author":"Guimar\u00e3es","year":"2009","journal-title":"Rev Neurol"},{"key":"R41-20260525","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.fct.2019.05.017","article-title":"A comprehensive review on biological activities and toxicology of crocetin","volume":"130","author":"Hashemi","year":"2019","journal-title":"Food Chem Toxicol"},{"key":"R42-20260525","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1038\/nn1805","article-title":"The P2Y12 receptor regulates microglial activation by extracellular nucleotides","volume":"9","author":"Haynes","year":"2006","journal-title":"Nat Neurosci"},{"key":"R43-20260525","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.eujim.2018.12.002","article-title":"Effects of dietary and lifestyle recommendations on patients with glaucoma: A randomized controlled pilot trial","volume":"25","author":"Hecht","year":"2019","journal-title":"Eur J Integr Med"},{"key":"R44-20260525","doi-asserted-by":"crossref","DOI":"10.3390\/nu11030649","article-title":"Saffron (Crocus sativus L) in ocular diseases: A narrative review of the existing evidence from clinical studies","author":"Heitmar","year":"2019","journal-title":"Nutrients"},{"key":"R45-20260525","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1046\/j.1471-0528.2002.02019.x","article-title":"Herbal medicinal products during pregnancy: are they safe?","volume":"109","author":"Hepner","year":"2002","journal-title":"BJOG"},{"key":"R46-20260525","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s13318-017-0449-3","article-title":"Pharmacokinetic properties of saffron and its active components","volume":"43","author":"Hosseini","year":"2018","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"R47-20260525","first-page":"1091","article-title":"Saffron (Crocus sativus) petal as a new pharmacological target: A review","volume":"21","author":"Hosseini","year":"2018","journal-title":"Iran J Basic Med Sci"},{"key":"R48-20260525","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2210-2-7","article-title":"Antinociceptive and anti-inflammatory effects of Crocus sativus L stigma and petal extracts in mice","volume":"2","author":"Hosseinzadeh","year":"2002","journal-title":"BMC Pharmacol"},{"key":"R49-20260525","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2013.02.007","article-title":"Crocetin, a carotenoid derivative, inhibits retinal ischemic damage in mice","volume":"703","author":"Ishizuka","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"R50-20260525","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1186\/1472-6882-14-399","article-title":"The ocular hypotensive effect of saffron extract in primary open angle glaucoma: a pilot study","volume":"14","author":"Jabbarpoor Bonyadi","year":"2014","journal-title":"BMC Complement Altern Med"},{"key":"R51-20260525","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.1167\/iovs.03-0436","article-title":"Drusen-associated degeneration in the retina","volume":"44","author":"Johnson","year":"2003","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"R52-20260525","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3390\/molecules23010030","article-title":"Saffron: an old medicinal plant and a potential novel functional food","volume":"23","author":"Jos\u00e9 Bagur","year":"2017","journal-title":"Molecules"},{"key":"R53-20260525","doi-asserted-by":"crossref","first-page":"6244","DOI":"10.3390\/molecules15096244","article-title":"Evaluation of Crocus sativus L stigma phenolic and flavonoid compounds and its antioxidant activity","volume":"15","author":"Karimi","year":"2010","journal-title":"Molecules"},{"key":"R54-20260525","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.fitote.2018.06.012","article-title":"Trans-crocin 4 is not hydrolyzed to crocetin following i p. administration in mice, while it shows penetration through the blood brain barrier","volume":"129","author":"Karkoula","year":"2018","journal-title":"Fitoterapia"},{"key":"R55-20260525","first-page":"59","article-title":"Effects of active constituents of Crocus sativus L, crocin on streptozocin-induced model of sporadic Alzheimer\u2019s disease in male rats","volume":"14","author":"Khalili","year":"2010","journal-title":"Iran Biomed J"},{"key":"R56-20260525","first-page":"27","article-title":"Behavioral and histological analysis of Crocus sativus effect in intracerebroventricular streptozotocin model of Alzheimer disease in rats","volume":"5","author":"Khalili","year":"2010","journal-title":"Iran J Pathol"},{"key":"R57-20260525","first-page":"376","article-title":"The effects of Crocus sativus (saffron) and its constituents on nervous system: A review","volume":"5","author":"Khazdair","year":"2015","journal-title":"Avicenna J Phytomed"},{"key":"R58-20260525","first-page":"82","article-title":"Anti-hyperglycemic effects of saffron and its active constituents crocin and safranal in alloxan-induced diabetic rats","volume":"3","author":"Kianbakht","year":"2011","journal-title":"J Med Plants"},{"key":"R59-20260525","doi-asserted-by":"crossref","DOI":"10.1002\/biof.1557","article-title":"Therapeutic effects of Crocin in autoimmune diseases: A review","author":"Korani","year":"2019","journal-title":"Biofactors"},{"key":"R60-20260525","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.mito.2011.11.004","article-title":"Mitochondrial dysfunction in glaucoma: Understanding genetic influences","volume":"12","author":"Lascaratos","year":"2012","journal-title":"Mitochondrion"},{"key":"R61-20260525","first-page":"32","article-title":"Short-term outcomes of saffron supplementation in patients with age-related macular degeneration: a double-blind placebo-controlled randomized trial","volume":"5","author":"Lashay","year":"2016","journal-title":"Med Hypothesis Discov Innov Ophthalmol"},{"key":"R62-20260525","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.phymed.2014.10.009","article-title":"Intestinal formation of trans-crocetin from saffron extract (Crocus sativus L and in vitro permeation through intestinal and blood brain barrier","volume":"22","author":"Lautenschl\u00e4ger","year":"2015","journal-title":"Phytomedicine"},{"key":"R63-20260525","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.exer.2010.07.015","article-title":"Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies","volume":"93","author":"Lee","year":"2011","journal-title":"Exp Eye Res"},{"key":"R64-20260525","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1007\/s11064-016-1905-1","article-title":"Crocin upregulates CX3CR1 expression by suppressing NF-\u03baB\/YY1 signaling and inhibiting lipopolysaccharide-induced microglial activation","volume":"41","author":"Lv","year":"2016","journal-title":"Neurochem Res"},{"key":"R65-20260525","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1167\/iovs.07-0438","article-title":"Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina","volume":"49","author":"Maccarone","year":"2008","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"R66-20260525","doi-asserted-by":"crossref","first-page":"e0166827","DOI":"10.1371\/journal.pone.0166827","article-title":"Modulation of type-1 and type-2 cannabinoid receptors by saffron in a rat model of retinal neurodegeneration","volume":"11","author":"Maccarone","year":"2016","journal-title":"PLoS One"},{"key":"R67-20260525","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/1479-5876-11-228","article-title":"Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: A preliminary report","volume":"11","author":"Marangoni","year":"2013","journal-title":"J Transl Med"},{"key":"R68-20260525","first-page":"208","article-title":"The time course of action of two neuroprotectants, dietary saffron and photobiomodulation, assessed in the rat retina","volume":"2","author":"Marco","year":"2013","journal-title":"Am J Neurodegener Dis"},{"key":"R69-20260525","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3390\/antiox2040293","article-title":"Saffron: A natural potent antioxidant as a promising anti-obesity drug","volume":"2","author":"Mashmoul","year":"2013","journal-title":"Antioxidants"},{"key":"R70-20260525","first-page":"3143","article-title":"Foveal flicker sensitivity discriminates ARM-risk from healthy eyes","volume":"33","author":"Mayer","year":"1992","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R71-20260525","first-page":"3150","article-title":"Preliminary evaluation of flicker sensitivity as a predictive test for exudative age-related maculopathy","volume":"33","author":"Mayer","year":"1992","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R72-20260525","first-page":"108","article-title":"Review on the effects of saffron extract and its constituents on factors related to nervous system cardiovascular and gastrointestinal diseases","volume":"3","author":"Milajerdi","year":"2014","journal-title":"JCE"},{"key":"R73-20260525","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1177\/0748233712452609","article-title":"Effect of aqueous extract of Crocus sativus L (saffron) stigma against subacute effect of diazinon on specific biomarkers in rats","volume":"30","author":"Moallem","year":"2014","journal-title":"Toxicol Ind Health"},{"key":"R74-20260525","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.phymed.2008.06.003","article-title":"Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers","volume":"15","author":"Modaghegh","year":"2008","journal-title":"Phytomedicine"},{"key":"R75-20260525","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41598-018-36576-w","article-title":"Oral crocetin administration suppressed refractive shift and axial elongation in a murine model of lens-induced myopia","volume":"9","author":"Mori","year":"2019","journal-title":"Sci Rep"},{"key":"R76-20260525","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.3390\/jcm8081179","article-title":"The effect of dietary supplementation of crocetin for myopia control in children: a randomized clinical trial","volume":"8","author":"Mori","year":"2019","journal-title":"J Clin Med"},{"key":"R77-20260525","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1055\/s-0034-1375681","article-title":"Clinical applications of saffron (Crocus sativus) and its constituents: a review","volume":"65","author":"Moshiri","year":"2014","journal-title":"Drug Res (Stuttg)"},{"key":"R78-20260525","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejphar.2010.09.003","article-title":"Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells","volume":"648","author":"Nam","year":"2010","journal-title":"Eur J Pharmacol"},{"key":"R79-20260525","first-page":"1801","article-title":"Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina","volume":"16","author":"Natoli","year":"2010","journal-title":"Mol Vis"},{"key":"R80-20260525","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejphar.2012.06.035","article-title":"Oral administration of crocetin prevents inner retinal damage induced by N-methyl-d-aspartate in mice","volume":"690","author":"Ohno","year":"2012","journal-title":"Eur J Pharmacol"},{"key":"R81-20260525","doi-asserted-by":"crossref","first-page":"8762","DOI":"10.1021\/jf061932a","article-title":"Inhibitory activity on amyloid-\u03b2 aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents","volume":"54","author":"Papandreou","year":"2006","journal-title":"J Agric Food Chem"},{"key":"R82-20260525","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1167\/iovs.02-0769","article-title":"Loss of cone function in age-related maculopathy","volume":"44","author":"Phipps","year":"2003","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"R83-20260525","first-page":"429124","article-title":"A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function","author":"Piccardi","year":"2012","journal-title":"Evid Based Complement Alternat Med 2012"},{"key":"R84-20260525","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2174\/187152312803476282","article-title":"Anti-inflammatory properties of drugs from saffron crocus","volume":"11","author":"Poma","year":"2012","journal-title":"Antiinflamm Antiallergy Agents Med Chem"},{"key":"R85-20260525","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3233\/JPD-130173","article-title":"Saffron pre-treatment offers neuroprotection to Nigral and retinal dopaminergic cells of MPTP-Treated mice","volume":"3","author":"Purushothuman","year":"2013","journal-title":"J Parkinsons Dis"},{"key":"R86-20260525","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.exer.2012.11.011","article-title":"Crocin prevents retinal ischaemia\/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K\/AKT signalling pathway","volume":"107","author":"Qi","year":"2013","journal-title":"Exp Eye Res"},{"key":"R87-20260525","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1080\/13543776.2017.1355909","article-title":"Saffron and its derivatives, crocin, crocetin and safranal: a patent review","volume":"28","author":"Rameshrad","year":"2018","journal-title":"Expert Opin Ther Pat"},{"key":"R88-20260525","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1350-9462(98)00009-3","article-title":"Apoptotic cell death in retinal degenerations","volume":"17","author":"Rem\u00e9","year":"1998","journal-title":"Prog Retin Eye Res"},{"key":"R89-20260525","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/(SICI)1099-1573(199605)10:3<189::AID-PTR754>3.0.CO;2-C","article-title":"An update review of saffron and its active constituents","volume":"10","author":"R\u00edos","year":"1996","journal-title":"Phyther Res"},{"key":"R90-20260525","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/1742-2094-11-133","article-title":"Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers","volume":"11","author":"Rojas","year":"2014","journal-title":"J Neuroinflammation"},{"key":"R91-20260525","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0002-9394(14)75004-4","article-title":"The pathophysiology of proliferative vitreoretinopathy in its management","volume":"100","author":"Ryan","year":"1985","journal-title":"Am J Ophthalmol"},{"key":"R92-20260525","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10354-007-0428-4","article-title":"Saffron in phytotherapy: Pharmacology and clinical uses","volume":"157","author":"Schmidt","year":"2007","journal-title":"Wien Med Wochenschr"},{"key":"R93-20260525","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ajo.2018.03.007","article-title":"Effects of crocin on diabetic maculopathy: a placebo-controlled randomized clinical trial","volume":"190","author":"Sepahi","year":"2018","journal-title":"Am J Ophthalmol"},{"key":"R94-20260525","doi-asserted-by":"crossref","first-page":"C1162","DOI":"10.1111\/j.1750-3841.2012.02926.x","article-title":"Increasing the applications of Crocus sativus flowers as natural antioxidants","volume":"77","author":"Serrano-D\u00edaz","year":"2012","journal-title":"J Food Sci"},{"key":"R95-20260525","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s11011-018-0379-z","article-title":"Pretreatment with crocin along with treadmill exercise ameliorates motor and memory deficits in hemiparkinsonian rats by anti-inflammatory and antioxidant mechanisms","volume":"34","author":"Shahidani","year":"2019","journal-title":"Metab Brain Dis"},{"key":"R96-20260525","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1016\/S0024-3205(01)01357-1","article-title":"Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells","volume":"69","author":"Soeda","year":"2001","journal-title":"Life Sci"},{"key":"R97-20260525","doi-asserted-by":"crossref","first-page":"200","DOI":"10.4103\/0973-7847.70919","article-title":"Crocus sativus L : A comprehensive review","volume":"4","author":"Srivastava","year":"2010","journal-title":"Pharmacogn Rev"},{"key":"R98-20260525","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.272.5262.735","article-title":"The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7)","volume":"272","author":"Surprenant","year":"1996","journal-title":"Science"},{"key":"R99-20260525","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.acthis.2018.12.003","article-title":"Crocus sativus restores dopaminergic and noradrenergic damages induced by lead in Meriones shawi: A possible link with Parkinson\u2019s disease","volume":"121","author":"Tamegart","year":"2019","journal-title":"Acta Histochem"},{"key":"R100-20260525","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1167\/iovs.09-4725","article-title":"Epithelial-mesenchymal transition and proliferation of retinal pigment epithelial cells initiated upon loss of cell-cell contact","volume":"51","author":"Tamiya","year":"2010","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"R101-20260525","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/157015909787602823","article-title":"Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options","volume":"7","author":"Uttara","year":"2009","journal-title":"Curr Neuropharmacol"},{"key":"R102-20260525","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1042\/BST20140107","article-title":"Glia in the pathogenesis of neurodegenerative diseases","volume":"42","author":"Verkhratsky","year":"2014","journal-title":"Biochem Soc Trans"},{"key":"R103-20260525","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/978-1-4614-0631-0_104","article-title":"The role of the P2X7 receptor in the retina: cell signalling and dysfunction","volume":"723","author":"Vessey","year":"2012","journal-title":"Adv Exp Med Biol"},{"key":"R104-20260525","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ejphar.2017.09.041","article-title":"Crocetin inhibits the proliferation migration and TGF-\u03b22-induced epithelial-mesenchymal transition of retinal pigment epithelial cells","volume":"815","author":"Wang","year":"2017","journal-title":"Eur J Pharmacol"},{"key":"R105-20260525","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.biopha.2018.10.193","article-title":"Safety, pharmacokinetics, and prevention effect of intraocular crocetin in proliferative vitreoretinopathy","volume":"109","author":"Wang","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"R106-20260525","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1002\/glia.22715","article-title":"Fractalkine receptor regulates microglial neurotoxicity in an experimental mouse glaucoma model","volume":"62","author":"Wang","year":"2014","journal-title":"Glia"},{"key":"R107-20260525","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neulet.2015.02.016","article-title":"Neuroprotective effects of crocin against traumatic brain injury in mice: Involvement of notch signaling pathway","volume":"591","author":"Wang","year":"2015","journal-title":"Neurosci Lett"},{"key":"R109-20260525","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.phymed.2006.11.028","article-title":"Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats","volume":"14","author":"Xi","year":"2007","journal-title":"Phytomedicine"},{"key":"R110-20260525","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1089\/jop.1999.15.143","article-title":"Effects of crocin analogs on ocular blood flow and retinal function","volume":"15","author":"Xuan","year":"1999","journal-title":"J Ocul Pharmacol Ther"},{"key":"R111-20260525","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ejphar.2010.09.081","article-title":"Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity","volume":"650","author":"Yamauchi","year":"2011","journal-title":"Eur J Pharmacol"},{"key":"R112-20260525","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s12031-017-0899-8","article-title":"Crocin inhibits oxidative stress and pro-inflammatory response of microglial cells associated with diabetic retinopathy through the activation of PI3K\/Akt signaling pathway","volume":"61","author":"Yang","year":"2017","journal-title":"J Mol Neurosci"},{"key":"R113-20260525","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1002\/jcp.27164","article-title":"A review of the molecular mechanisms of hyperglycemia-induced free radical generation leading to oxidative stress","volume":"234","author":"Yaribeygi","year":"2019","journal-title":"J Cell Physiol"},{"key":"R114-20260525","doi-asserted-by":"crossref","first-page":"8610","DOI":"10.1002\/jcp.27843","article-title":"Antidiabetic potential of saffron and its active constituents","volume":"234","author":"Yaribeygi","year":"2019","journal-title":"J Cell Physiol"},{"key":"R115-20260525","first-page":"334","article-title":"Immunoregulatory and anti-inflammatory properties of Crocus sativus (Saffron) and its main active constituents: A review","volume":"22","author":"Zeinali","year":"2019","journal-title":"Iran J Basic Med Sci"},{"key":"R116-20260525","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ejphar.2018.11.001","article-title":"Crocetin inhibits PDGF-BB-induced proliferation and migration of retinal pigment epithelial cells","author":"Zhang","year":"2019","journal-title":"Eur J Pharmacol"},{"key":"R117-20260525","first-page":"65","article-title":"Crocin protects against cerebral- ischemia-induced damage in aged rats through maintaining the integrity of blood-brain barrier","volume":"35","author":"Zhang","year":"2017","journal-title":"Restor Neurol Neurosci"},{"key":"R118-20260525","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchromb.2016.12.003","article-title":"Sensitive analysis and simultaneous assessment of pharmacokinetic properties of crocin and crocetin after oral administration in rats","volume":"1044-1045","author":"Zhang","year":"2017","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"}],"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/1673-5374.274325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:29:10Z","timestamp":1786735750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/1673-5374.274325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,28]]},"references-count":117,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.4103\/1673-5374.274325","relation":{},"ISSN":["1673-5374","1876-7958"],"issn-type":[{"value":"1673-5374","type":"print"},{"value":"1876-7958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,28]]},"assertion":[{"value":"2019-10-07","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-11","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}