Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report

Marangoni, Dario; Falsini, Benedetto; Piccardi, Marco; Ambrosio, Lucia; Minnella, Angelo Maria; Savastano, Maria Cristina; Bisti, Silvia; Maccarone, Rita; Fadda, Antonello; Mello, Enrica; Concolino, Paola; Capoluongo, Ettore

doi:10.1186/1479-5876-11-228

Cited by 56 publications

(42 citation statements)

References 48 publications

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“…In particular, orally administered saffron partially preserved both morphology and function in light damaged retina [1]. A pilot clinical trial conducted on AMD patients provided the first evidence of successful saffron treatment in therapy [11], the positive effects being maintained in time [12] and in patients carrying genetic mutation [13]. Multiple actions of saffron have been suggested, including modulation of gene expression in animal models of retinal degeneration [14].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

et al. 2016

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Experimental studies demonstrated that saffron (Crocus sativus) given as a dietary supplement counteracts the effects of bright continuous light (BCL) exposure in the albino rat retina, preserving both morphology and function and probably acting as a regulator of programmed cell death [1]. The purpose of this study was to ascertain whether the neuroprotective effect of saffron on rat retina exposed to BCL is associated with a modulation of the endocannabinoid system (ECS). To this aim, we used eight experimental groups of Sprague-Dawley rats, of which six were exposed to BCL for 24 hours. Following retinal function evaluation, retinas were quickly removed for biochemical and morphological analyses. Rats were either saffron-prefed or intravitreally injected with selective type-1 (CB1) or type-2 (CB2) cannabinoid receptor antagonists before BCL. Prefeeding and intravitreally injections were combined in two experimental groups before BCL. BCL exposure led to enhanced gene and protein expression of retinal CB1 and CB2 without affecting the other ECS elements. This effect of BCL on CB1 and CB2 was reversed by saffron treatment. Selective CB1 and CB2 antagonists reduced photoreceptor death, preserved morphology and visual function of retina, and mitigated the outer nuclear layer (ONL) damage due to BCL. Of interest, CB2-dependent neuroprotection was more pronounced than that conferred by CB1. These data suggest that BCL modulates only distinct ECS elements like CB1 and CB2, and that saffron and cannabinoid receptors could share the same mechanism in order to afford retinal protection.

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Section: Introductionmentioning

confidence: 99%

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

et al. 2016

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“…Maccarone et al [22] provided data showing that Saf is protective in a rat model of lightinduced retinal degeneration. A proof-of-principle clinical trial in age-related macular degeneration (AMD) patients confirmed the potentiality of Saf treatment in neurodegenerative diseases and its consistency in time [23,24] and in patients carrying genetic mutations [25]. The biological mechanisms underlying neuroprotection are thus far unknown even though a direct control of gene expression was suggested [26,27].…”

Section: Introductionmentioning

confidence: 99%

Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors

Corso

Cavallero

Baroni

et al. 2016

Purinergic Signalling

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P2X7-type purinergic receptors are distributed throughout the nervous system where they contribute to physiological and pathological functions. In the retina, this receptor is found in both inner and outer cells including microglia modulating signaling and health of retinal cells. It is involved in retinal neurodegenerative disorders such as retinitis pigmentosa and age-related macular degeneration (AMD). Experimental studies demonstrated that saffron protects photoreceptors from light-induced damage preserving both retinal morphology and visual function and improves retinal flicker sensitivity in AMD patients. To evaluate a possible interaction between saffron and P2X7 receptors (P2X7Rs), different cellular models and experimental approaches were used. We found that saffron positively influences the viability of mouse primary retinal cells and photoreceptor-derived 661W cells exposed to ATP, and reduced the ATP-induced intracellular calcium increase in 661W cells. Similar results were obtained on HEK cells transfected with recombinant rat P2X7R but not on cells transfected with rat P2X2R. Finally, patch-clamp experiments showed that saffron inhibited cationic currents in HEK-P2X7R cells. These results point out a novel mechanism through which saffron may exert its protective role in neurodegeneration and support the idea that P2X7-mediated calcium signaling may be a crucial therapeutic target in the treatment of neurodegenerative diseases.

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“…; Marangoni et al . ), equating to a much lower daily dose (~ 0.25–0.33 mg/kg/day) than that used in this study. It is also possible that differences in the dose–response relationship arise when the daily dose of saffron is consumed as a single bolus (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The sustained neuroprotective efficacy of saffron following 10 days of pretreatment may relate to the daily dose given, which was estimated at 1 mg/kg/day (via injection of 0.2% saffronwater into a vegetable matrix) in the rat study compared tõ 14 mg/kg/day in this study. Similarly, in successful clinical trials of saffron in early-stage age-related macular degeneration, participants received 20 mg/day of saffron supplementation (Falsini et al 2010;Piccardi et al 2012;Marangoni et al 2013), equating to a much lower daily dose (~0.25-0.33 mg/kg/day) than that used in this study. It is also possible that differences in the dose-response relationship arise when the daily dose of saffron is consumed as a single bolus (e.g.…”

Section: Comparison To Previous Studies and Limitationsmentioning

confidence: 99%

Widespread brain transcriptome alterations underlie the neuroprotective actions of dietary saffron

Skladnev

Ganeshan

Kim

et al. 2016

Journal of Neurochemistry

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Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for 2, 5 or 10 days before administration of the parkinsonian neurotoxin MPTP (50 mg/kg). Five days of saffron pre-conditioning provided the greatest benefit against MPTP-induced neuropathology, significantly mitigating both loss of functional dopaminergic cells in the substantia nigra pars compacta (p < 0.01) and abnormal neuronal activity in the caudate-putamen complex (p < 0.0001). RNA microarray analysis of the brain transcriptome of mice pre-conditioned with saffron for 5 days revealed differential expression of 424 genes. Bioinformatics analysis identified enrichment of molecular pathways (e.g. adherens junction, TNFR1 and Fas signaling) and expression changes in candidate genes (Cyr61, Gpx8, Ndufs4, and Nos1ap) with known neuroprotective actions. The apparent biphasic nature of the dose-response relationship between saffron and measures of neuroprotection, together with the stress-inducible nature of many of the up-regulated genes and pathways, lend credence to the idea that saffron, like various other phytochemicals, is a hormetic stimulus, with functions beyond its strong antioxidant capacity. These findings provide impetus for a more comprehensive evaluation of saffron as a neuroprotective intervention.

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Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report

Cited by 56 publications

References 48 publications

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors

Widespread brain transcriptome alterations underlie the neuroprotective actions of dietary saffron

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