{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T22:37:26Z","timestamp":1776465446830,"version":"3.51.2"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Economic Development, Sustainable Growth Fund","award":["CUP B83D17001330008"],"award-info":[{"award-number":["CUP B83D17001330008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Saffron treatment is a broad-spectrum therapy used for several retinal diseases, and its effectiveness depends on a particular molecular composition (REPRON\u00ae saffron). Its production requires specific crops and procedures that, together with low yields, make this spice expensive. To reduce costs, the use of hydroponic crops is gradually increasing. In this study, we tested the protective properties of a hydroponic saffron (sH) batch in models of retinal pigmented epithelium (RPE) degeneration. ARPE-19 cells were pretreated with 40 \u00b5g\/mL saffron and exposed to different types of damage: excess light and retinol (LE + RET) or oxidative stress (H2O2). After analyzing the composition of all saffron types with spectroscopy, we performed cell viability and immunofluorescence analysis for both protocols. We compared the sH results with those of a validated batch of saffron REPRON\u00ae (sR) and those of a saffron non-REPRON\u00ae (sNR) batch. sH and sR, which we found had the same chemical composition, were more effective than sNR in increasing cell survival and attenuating the morphological changes related to apoptosis. In conclusion, hydroponic culturing is a suitable strategy to produce high-quality saffron to reduce costs and increase the accessibility of this promising treatment for retinal degeneration.<\/jats:p>","DOI":"10.3390\/molecules28041699","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T05:18:35Z","timestamp":1676006315000},"page":"1699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy of Hydroponically Cultivated Saffron in the Preservation of Retinal Pigment Epithelium"],"prefix":"10.3390","volume":"28","author":[{"given":"Mattia","family":"Di Paolo","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Louisville, Kentucky, KY 40202, USA"},{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"},{"name":"National Institute of Biostructure and Biosystem (INBB), V. le Medaglie D\u2019Oro 305, 00136 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9350-7948","authenticated-orcid":false,"given":"Francesca","family":"Corsi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2474-4672","authenticated-orcid":false,"given":"Maria","family":"Maggi","sequence":"additional","affiliation":[{"name":"Hortus Novus srl, via Campo Sportivo 2, 67050 Canistro, Italy"},{"name":"Department of Physical and Chemical Sciences, University of L\u2019Aquila, 67100 Coppito, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3063-8067","authenticated-orcid":false,"given":"Luca","family":"Nardi","sequence":"additional","affiliation":[{"name":"ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Biotechnology and Agro-Industry Division, Casaccia Research Center, 00123 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4157-111X","authenticated-orcid":false,"given":"Silvia","family":"Bisti","sequence":"additional","affiliation":[{"name":"National Institute of Biostructure and Biosystem (INBB), V. le Medaglie D\u2019Oro 305, 00136 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-7583","authenticated-orcid":false,"given":"Ilaria","family":"Piano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"},{"name":"National Institute of Biostructure and Biosystem (INBB), V. le Medaglie D\u2019Oro 305, 00136 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Gargini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"},{"name":"National Institute of Biostructure and Biosystem (INBB), V. le Medaglie D\u2019Oro 305, 00136 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","unstructured":"Sarwat, M., and Sumaiya, S. (2020). Saffron: The Age-Old Panacea in New Light, Elsevier. [1st ed.]."},{"key":"ref_2","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":"ref_3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.foodchem.2016.01.003","article-title":"Saffron authentication based on liquid chromatography high resolution tandem mass spectrometry and multivariate data analysis","volume":"204","author":"Rubert","year":"2016","journal-title":"Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.chroma.2016.11.044","article-title":"Characterisation of chemical components for identifying historical Chinese textile dyes by ultra high performance liquid chromatography\u2014photodiode array\u2014electrospray ionisation mass spectrometer","volume":"1479","author":"Han","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.foodchem.2018.03.025","article-title":"Quality assessment of saffron (Crocus sativus L.) extracts via UHPLC-DAD-MS analysis and detection of adulteration using gardenia fruit extract (Gardenia jasminoides Ellis)","volume":"257","author":"Moras","year":"2018","journal-title":"Food Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"D\u2019Archivio, A.A., Di Donato, F., Foschi, M., Maggi, M.A., and Ruggieri, F. (2018). UHPLC Analysis of Saffron (Crocus sativus L.): Optimization of Separation Using Chemometrics and Detection of Minor Crocetin Esters. Molecules, 23.","DOI":"10.3390\/molecules23081851"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1105\/tpc.006536","article-title":"Oxidative remodeling of chromoplast carotenoids identification of the carotenoid dioxygenase CsCCD and CsZCD genes involved in Crocus secondary metabolite biogenesis","volume":"15","author":"Bouvier","year":"2003","journal-title":"Plant Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s00425-004-1299-1","article-title":"Glucosylation of the saffron apocarotenoid crocetin by a glucosyltransferase isolated from Crocus sativus stigmas","volume":"219","author":"Moraga","year":"2004","journal-title":"Planta"},{"key":"ref_9","first-page":"2395","article-title":"Synthesis of Crocin, Picrocrocin and Safranal by Saffron Stigma-like Structures Proliferatedin Vitro","volume":"51","author":"Himeno","year":"1987","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Maggi, M.A., Bisti, S., and Picco, C. (2020). Saffron: Chemical Composition and Neuroprotective Activity. Molecules, 25.","DOI":"10.3390\/molecules25235618"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Maggi, M.A., Consonni, R., Cagliani, L.R., Prestipino, G., Bisti, S., and Picco, C. (2022). Saffron and retinal neurodegenerative diseases: Relevance of chemical composition. J. Anat.","DOI":"10.1111\/joa.13722"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3389\/fpls.2019.00923","article-title":"Hydroponic Solutions for Soilless Production Systems: Issues and Opportunities in a Smart Agriculture Perspective","volume":"10","author":"Sambo","year":"2019","journal-title":"Front. Plant Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/13816810.2020.1723116","article-title":"Progressive RPE atrophy and photoreceptor death in KIZ-associated autosomal recessive retinitis pigmentosa","volume":"41","author":"Lin","year":"2020","journal-title":"Ophthalmic Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"591067","DOI":"10.3389\/fcell.2020.591067","article-title":"Not All Stressors Are Equal: Mechanism of Stressors on RPE Cell Degeneration","volume":"8","author":"Tong","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1167\/iovs.18-26360","article-title":"Retinal Pigment Epithelium Cell Death Is Associated With NLRP3 Inflammasome Activation by All-trans Retinal","volume":"60","author":"Liao","year":"2019","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.foodchem.2016.05.149","article-title":"Geographical classification of Italian saffron (Crocus sativus L.) based on chemical constituents determined by high-performance liquid-chromatography and by using linear discriminant analysis","volume":"212","author":"Giannitto","year":"2016","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1021\/jf703725e","article-title":"Rapid Determination of Crocetin Esters and Picrocrocin from Saffron Spice (Crocus sativus L.) Using UV\u2013Visible Spectrophotometry for Quality Control","volume":"56","author":"Carmona","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","unstructured":"(2010). Spices\u2014Saffron (Crocus sativus L.)\u2014Part 2: Test Methods (Standard No. ISO 3632-2)."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Islam, R., Corraya, R.M., Pasovic, L., Khan, A.Z., Aass, H.C.D., Eidet, J.R., and Utheim, T.P. (2020). The Effects of Prolonged Storage on ARPE-19 Cells Stored at Three Different Storage Temperatures. Molecules, 25.","DOI":"10.3390\/molecules25245809"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/toxsci\/kfx030","article-title":"Editor\u2019s Highlight: Periodic Exposure to Smartphone-Mimic Low-Luminance Blue Light Induces Retina Damage Through Bcl-2\/BAX-Dependent Apoptosis","volume":"157","author":"Lin","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Piccardi, M., Fadda, A., Martelli, F., Marangoni, D., Magli, A., Minnella, A.M., Bertelli, M., Di Marco, S., Bisti, S., and Falsini, B. (2019). Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy. Nutrients, 11.","DOI":"10.3390\/nu11102461"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/429124","article-title":"A Longitudinal Follow-Up Study of Saffron Supplementation in Early Age-Related Macular Degeneration: Sustained Benefits to Central Retinal Function","volume":"2012","author":"Piccardi","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","article-title":"The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD","volume":"60","author":"Datta","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Feldman, T., Ostrovskiy, D., Yakovleva, M., Dontsov, A., Borzenok, S., and Ostrovsky, M. (2022). Lipofuscin-Mediated Photic Stress Induces a Dark Toxic Effect on ARPE-19 Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012234"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.exer.2005.02.013","article-title":"Lecithin:retinol acyltransferase in ARPE-19","volume":"80","author":"Trevino","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3390\/ijerph2005010147","article-title":"Photodecomposition and Phototoxicity of Natural Retinoids","volume":"2","author":"Tolleson","year":"2005","journal-title":"Int. J. Environ. Res. Public Health"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:30:16Z","timestamp":1760121016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041699"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041699","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,10]]}}}