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Saffron and retina: Neuroprotection and pharmacokinetics

Published online by Cambridge University Press:  12 May 2014

SILVIA BISTI ,
RITA MACCARONE  and
BENEDETTO FALSINI
SILVIA BISTI*
Affiliation:
University of L’Aquila, DISCAB, L’Aquila, Italy
RITA MACCARONE
Affiliation:
University of L’Aquila, DISCAB, L’Aquila, Italy
BENEDETTO FALSINI
Affiliation:
Dipartimento di Scienze Otorinolaringoiatriche e Oftalmologiche, University La Cattolica del Sacro Cuore, Roma, Italy
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Abstract

Age-related macular degeneration (AMD) is a retinal neurodegenerative disease whose development and progression are the results of a complex interaction between genetic and environmental risk factors. Both oxidative stress and chronic inflammation play a significant role in the pathogenesis of AMD. Experimental studies in rats with light-induced photoreceptors degeneration demonstrated that saffron may protect photoreceptor from retinal stress, preserving both morphology and function and probably acting as a regulator of programmed cell death, in addition to its antioxidant and anti-inflammatory properties. Recently, a randomized clinical trial showed that in patients with early AMD, dietary supplementation with saffron was able to improve significantly the retinal flicker sensitivity suggesting neuroprotective effect of the compound. Here, we examine the progress of saffron dietary supplementation both in animal model and AMD patients, and discuss the potential and safety for using dietary saffron to treat retinal degeneration.

Keywords

Age-related macular degenerationFocal electroretinogramNeuroprotectionPhotoreceptorsSaffron
Type
Review Articles
Information
Visual Neuroscience , Volume 31 , Issue 4-5: Strategies for Restoring Sight in Retinal Dystrophies , September 2014 , pp. 355 - 361
Copyright
Copyright © Cambridge University Press 2014 

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References

Abdullaev, F.I., Riveròn-Negrete, L., Caballero-Ortega, H., Manuel Hernàndez, J., Pérez-Lòpez, I., Pereda-Miranda, R. & Espinosa-Aguirre, J.J. (2003). Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicology in Vitro 17, 731–736.Google Scholar
Age-Related Eye Disease Study 2 Research Group (2013). Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The age-related eye disease study 2 (AREDS2) randomized clinical trial. The Journal of the American Medical Association 309, 2005–2015.CrossRefGoogle Scholar
Akhondzadeh, S., Sabet, M.S., Harirchian, M.H., Togha, M., Cheraghmakani, H., Razeghi, S., Hejazi, S., Yousefi, M.H., Alimardani, R., Jamshidi, A., Zare, F. & Moradi, A. (2010). Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: A 16-week, randomized and placebo-controlled trial. Journal of Clinical Pharmacy and Therapeutics 35, 581–588.CrossRefGoogle ScholarPubMed
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. (2009). A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl) 207, 637–643.CrossRefGoogle ScholarPubMed
Akhondzadeh, S., Tahmacebi-Pour, N., Noorbala, A.A., Amini, H., Fallah-Pour, H., Jamshidi, A.H. & Khani, M. (2005). Crocus sativus L. in the treatment of mild to moderate depression: A double-blind, randomized and placebo-controlled trial. Phytotherapy Research 19, 148–151.Google Scholar
Amin, A., Hamza, A.A., Bajbouj, K., Ashraf, S.S. & Daoud, S. (2011). Saffron: A potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology 54, 857–867.CrossRefGoogle ScholarPubMed
Asai, A., Nakano, T., Takahashi, M. & Nagao, A. (2005). Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. Journal of Agricultural and Food Chemistry 53, 7302–7306.Google Scholar
Ayatollahi, H., Javan, A.O., Khajedaluee, M., Shahroodian, M. & Hosseinzadeh, H. (2013 June 3). Effect of Crocus sativus L. (Saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytotherapy Research DOI: 10.1002/ptr.5021.Google Scholar
Bowers, F., Valter, K., Chan, S., Walsh, N., Maslim, J. & Stone, J. (2001). Effects of oxygen and bFGF on the vulnerability of photoreceptors to light damage. Investigative Ophthalmology & Visual Science 42, 804–815.Google Scholar
Bird, A.C., Bressler, N.M., Bressler, S.B., Bressler, S.B., Chisholm, I.H., Coscas, G., Davis, M.D., de Jong, P.T., Klaver, C.C., Klein, B.E., Klein, R. (1995). The International ARM Epidemiological Study Group. An international classification and grading system for age-related maculopathy and age-related macular degeneration. Survey of Ophthalmology 39, 367–374.CrossRefGoogle ScholarPubMed
Beatty, S., Koh, H., Phil, M., Henson, D. & Boulton, M. (2000). The role of oxidative stress in the pathogenesis of age-related macular degeneration. Survey of Ophthalmology 45, 115–134.Google Scholar
Buschini, E., Piras, A., Nuzzi, R. & Vercelli, A. (2011). Age related macular degeneration and drusen: Neuroinflammation in the retina. Progress in Neurobiology 95, 14–25.Google Scholar
Di Marco, F., Romeo, S., Nandasena, C., Purushothuman, S., Adams, C., Bisti, S. & Stone, J. (2013). The time course of action of two neuroprotectants, dietary saffron and photobiomodulation, assessed in the rat retina. American Journal of Neurodegenerative Disease 2, 208–220.Google Scholar
Falsini, B., Fadda, A., Iarossi, G., Piccardi, M., Canu, D., Minnella, A., Serrao, S. & Scullica, L. (2000 May). Retinal sensitivity to flicker modulation: Reduced by early age-related maculopathy. Investigative Ophthalmology & Visual Science 41, 1498–1506.Google Scholar
Falsini, B., Piccardi, M., Iarossi, G., Fadda, A., Merendino, E. & Valentini, P. (2003 Jan). Influence of short-term antioxidant supplementation on macular function in age-related maculopathy: A pilot study including electrophysiologic assessment. Ophthalmology 110, 51–60.CrossRefGoogle ScholarPubMed
Falsini, B., Piccardi, M., Minnella, A., Savastano, C., Capoluongo, E., Fadda, A., Balestrazzi, E., Maccarone, R. & Bisti, S. (2010). Influence of saffron supplementation on retinal flicker sensitivity in early age related macular degeneration. Investigative Ophthalmology & Visual Science 51, 6118–6124.CrossRefGoogle ScholarPubMed
Fernández-Sánchez, L., Lax, P., Esquiva, G., Martín-Nieto, J., Pinilla, I. & Cuenca, N. (2012). Safranal, a saffron constituent, attenuates retinal degeneration in P23H rats. PLoS One 7, e43074.Google Scholar
Garcýà -Olmo, D.C., Riese, H.H., Escribano, J., Ontanòn, J., Fernandez, J.A., Atiènzar, M. & Garcýà -Olmo, D. (1999). Effects of longterm treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): An experimental study in the rat. Nutrition and Cancer 35, 120–126.Google Scholar
Giaccio, M. (2004). Crocetin from saffron: An active component of an ancient spice. Critical Reviews in Food Science and Nutrition 44, 155–172.CrossRefGoogle ScholarPubMed
Hollyfield, J.G. (2010). Age-related macular degeneration: the molecular link between oxidative damage, tissue-specific inflammation and outer retinal disease: The Proctor lecture. Investigative Ophthalmology & Visual Science 51, 1275–1281.Google Scholar
Hosseinzadeh, H., Sadeghnia, H.R., Ghaeni, F.A., Motamedshariaty, V.S. & Mohajeri, S.A. (2012). Effects of saffron (Crocus sativus L) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytotherapy Research 26, 381–386.Google Scholar
Iarossi, G., Falsini, B. & Piccardi, M. (2003). Regional cone dysfunction in retinitis pigmentosa evaluated by flicker ERGs: Relationship with perimetric sensitivity losses. Investigative Ophthalmology & Visual Science 44, 866–874.CrossRefGoogle ScholarPubMed
Jarrett, S.G. & Boulton, M.E. (2012). Consequences of oxidative stress in age-related macular degeneration. Molecular Aspects of Medicine 33, 399–417.CrossRefGoogle ScholarPubMed
Kanakis, C.D., Tarantilis, P.A., Tajimir-Riahi, H.A. & Polissiou, M.G. (2007). Crocetin, dimethylcrocetin, and safranal bind humanserum albumin: Stability and antioxidative properties. Journal of Agricultural and Food Chemistry 55, 970–977.CrossRefGoogle Scholar
Maccarone, R., Di Marco, S. & Bisti, S. (2008). Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Investigative Ophthalmology & Visual Science 49, 1254–1261.Google Scholar
Marangoni, D., Falsini, B., Piccardi, M., Ambrosio, L., Minnella, A.M., Savastano, M.C., Bisti, S., Maccarone, R., Fadda, A., Mello, E., Concolino, P. & Capoluongo, E. (2013 Sept). Functional effect of saffron supplementation and risk genotypes in early age-related macular degeneration: A preliminary report. Journal of Translational Medicine 11, 228.CrossRefGoogle ScholarPubMed
Nam, K.N., Park, Y.M., Jung, H.J., Lee, J.Y., Min, B.D., Park, S.U., Jung, W.S., Cho, K.H., Park, J.H., Kang, I., Hong, J.W. & Lee, E.H. (2010) Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. European Journal of Pharmacology 648, 110–116.CrossRefGoogle ScholarPubMed
Natoli, R., Zhu, Y., Valter, K., Bisti, S., Eells, J. & Stone, J. (2010). Gene and noncoding RNA regulation underlying photoreceptor protection: Microarray study of dietary antioxidant saffron and photobiomodulation in rat retina. Molecular Vision 16, 1801–1822.Google Scholar
Ochiai, T., Shimeno, H., Mishima, K., Iwasaki, K., Fujiwara, M., Tanaka, H., Shoyama, Y., Toda, A., Eyanagi, R. & Soeda, S. (2007). Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochemica Biophysica Acta 1770, 578–584.Google Scholar
Ohno, Y., Nakanishi, T., Umigai, N., Tsuruma, K., Shimazawa, M. & Hara, H. (2012). Oral administration of crocetin prevents inner retinal damage induced by N-methyl-D-aspartate in mice. European Journal of Pharmacology 690, 84–89.CrossRefGoogle ScholarPubMed
Organisciak, D.T. & Vaughan, D.K. (2010). Retinal light damage: Mechanisms and protection. Progress in Retinal Eye Research 29, 113–134.Google Scholar
Piccardi, M., Marangoni, D., Minnella, A.M., Savastano, M.C., Valentini, P., Ambrosio, L., Capoluongo, E., Maccarone, R., Bisti, S. & Falsini, B. (2012). A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: Sustained benefits to central retinal function. Evidence Based Complement Alternat Med. 2012, 429124.CrossRefGoogle ScholarPubMed
Piccardi, M., Ziccardi, L., Stifano, G., Montrone, L., Iarossi, G., Minnella, A., Fadda, A., Balestrazzi, E. & Falsini, B. (2009). Regional cone-mediated dysfunction in age-related maculopathy evaluated by focal electroretinograms: Relationship with retinal morphology and perimetric sensitivity. Ophthalmic Research 41, 194–202.CrossRefGoogle ScholarPubMed
Purushothuman, S., Nandasena, C., Peoples, C.L., El Massri, N., Johnstone, D.M., Mitrofanis, J. & Stone, J. (2013). Saffron pre-treatment offers neuroprotection to Nigral and retinal dopaminergic cells of MPTP-treated mice. Journal of Parkinsons Disease 3, 77–83. doi: 10.3233/JPD-130173.Google Scholar
Ratnapriya, R. & Chew, E.Y. (2013 Aug). Age-related macular degeneration-clinical review and genetics update. Clinical Genetics 84, 160–166.Google Scholar
Rutar, M., Provis, J.M. & Valter, K. (2010). Brief exposure to damaging light causes focal recruitment of macrophages, and long-term destabilization of photoreceptors in the albino rat retina. Current Eye Research 35, 631–643.Google Scholar
Stone, J., Mervin, K., Walsh, N., Valter, K., Provis, J. & Penfold, P. (2005). Photoreceptor stability and degeneration in mammalian retina: Lessons from the edge. In Macular Degeneration: Science and Medicine in Practice, ed. Penfold, P. & Provis, J., pp. 149–165. Heidelberg, Germany: Springer Verlag.Google Scholar
Swaroop, A., Chew, E.Y., Rickman, C.B. & Abecasis, G.R. (2009). Unraveling a multifactorial late-onset disease: From genetic susceptibility to disease mechanisms for age-related macular degeneration. Annual Review of Genomics and Human Genetics 10, 19–43.CrossRefGoogle ScholarPubMed
Umigai, N., Murakami, K., Ulit, M.V., Antonio, L.S., Shirotori, M., Morikawa, H. & Nakano, T. (2011). The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration. Phytomedicine 18, 575–578.Google Scholar
Xi, L., Qian, Z., Du, P. & Fu, J. (2007). Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats. Phytomedicine 14, 633–636.Google Scholar
Xuan, B., Zhou, Y.H., Li, N., Min, Z.D. & Chiou, G.C. (1999). Effects of crocin analogues on ocular blood flow and retinal function. Journal of Ocular Pharmacology and Therapeutics 15, 143–152.Google Scholar
Yamauchi, M., Tsuruma, K., Imai, S., Nakanishi, T., Umigai, N., Shimazawa, M. & Hara, H. (2011). Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity. European Journal of Pharmacology 650, 110–119.CrossRefGoogle ScholarPubMed