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Life Extension Magazine August 2012


Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women. 

Snacking is an uncontrolled eating behavior, predisposing weight gain and obesity. It primarily affects the female population and is frequently associated with stress. We hypothesized that oral supplementation with Satiereal (Inoreal Ltd, Plerin, France), a novel extract of saffron stigma, may reduce snacking and enhance satiety through its suggested mood-improving effect, and thus contribute to weight loss. Healthy, mildly overweight women (N = 60) participated in this randomized, placebo-controlled, double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period. Snacking frequency, the main secondary variable, was assessed by daily self-recording of episodes by the subjects in a nutrition diary. Twice a day, enrolled subjects consumed 1 capsule of Satiereal (176.5 mg extract per day (n = 31) or a matching placebo (n = 29). Caloric intake was left unrestricted during the study. At baseline, both groups were homogeneous for age, body weight, and snacking frequency. Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks (P < .01). The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group (P < .05). Other anthropometric dimensions and vital signs remained almost unchanged in both groups. No subject withdrawal attributable to a product effect was reported throughout the trial, suggesting a good tolerability to Satiereal. Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss. The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective.

Nutr Res. 2010 May;30(5):305-13

Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial.

Depression is a serious disorder in today's society, with estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As a therapeutic plant, saffron is considered excellent for stomach ailments and as an antispasmodic, to help digestion and to increase appetite. It is also used for depression in Persian traditional medicine. Our objective was to assess the efficacy of the stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6-week double-blind, placebo-controlled and randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton rating scale for depression score of at least 18. In this double-blind, placebo-controlled, single-centre and randomized trial, patients were randomly assigned to receive a capsule of saffron 30 mg[sol ]day (BD) (Group 1) or a capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, Crocus sativus produced a significantly better outcome on the Hamilton depression rating scale than the placebo (d.f. = 1, F = 18.89, p < 0.001). There were no significant differences in the two groups in terms of the observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.

Phytother Res. 2005 Feb;19(2):148-51

Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice.

Saffron stigma (Crocus sativus L.) is used for insomnia and anxiety in traditional medicine. In this study, the anxiolytic and hypnotic effects of saffron aqueous extract and its constituents, crocin and safranal, were studied in mice. Agents were administered intraperitoneally in mice before the experiments for the evaluation of hypnotic activity (induced by sodium pentobarbital, 30 mg/kg, i.p.), anxiolytic activity (elevated plus maze test), locomotor activity (open field test) and motor coordination (Rotarod test). The aqueous extract reduced the locomotor activity dose dependently. At low doses, saffron showed a significant increase in the time on the open arms of the maze. When using the Rotarod method, the aqueous extract showed considerable effect on motor coordination of the mice. In the hypnotic test, only a dose of 0.56 g/kg of saffron increased the total sleep. Crocin showed no anxiolytic, hypnotic or myorelaxation effects. Safranal, in higher doses, 0.15 and 0.35 mL/kg, showed anxiolytic effects. Safranal increased the total sleep time dose dependently. This constituent at lower doses (0.05 and 0.15 mL/kg) decreased some locomotion activity parameters. Safranal demonstrated no effects on motor coordination. The results showed that saffron aqueous extract and safranal have anxiolytic and hypnotic effects.

Phytother Res. 2009 Jun;23(6):768-74

Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro.

Extracts of saffron (Crocus sativus L.) have been reported to inhibit cell growth of human tumor cells. In order to study the cytotoxic effect of the characteristic compounds of saffron spice, we have isolated crocin, crocetin, picrocrocin and safranal. Doses inducing 50% cell growth inhibition (LD50) on HeLa cells were 2.3 mg/ml for an ethanolic extract of saffron dry stigmas, 3 mM for crocin, 0.8 mM for safranal and 3 mM for picrocrocin. Crocetin did not show cytotoxic effect. Cells treated with crocin exhibited wide cytoplasmic vacuole-like areas, reduced cytoplasm, cell shrinkage and pyknotic nuclei, suggesting apoptosis induction. Considering its water-solubility and high inhibitory growth effect, crocin is the more promising saffron compound to be assayed as a cancer therapeutic agent.

Cancer Lett. 1996 Feb 27;100(1-2):23-30

Inhibition of breast cancer cell proliferation by style constituents of different Crocus species.

Among the different species of Crocus, only C. sativus has been extensively studied for the composition and the biological properties of its styles, since these constitute the well-known spice saffron, which is widely used in the Mediterranean, Indian and Chinese diet. With high performance liquid chromatography (HPLC) and UV/vis spectroscopy, the presence of hydrophilic carotenoids in the styles of three other Crocus taxa, endemic in Greece, C. boryi ssp. tournefortii, C. boryi ssp. boryi and C. niveus, is reported for the first time. Incubation of MCF-7 and MDA-MB-231 breast cancer cells for 48 h with different concentrations of all four Crocus style extracts showed a dose-dependent inhibitory effect on cell proliferation measured by the MTT assay. The antiproliferative effect was not related to the presence of estrogen receptors. Studies on the effect of trans-crocin-4 (the main carotenoid constituent of C. sativus styles, digentibiosylester of crocetin), crocetin and safranal showed that the antiproliferative effect is attributed to the constituent crocins irrespective of the degree of glycosylation. These results show that the styles of the various Crocus taxa merit further investigation of their composition and mechanisms of action of their carotenoid constituents in order to establish if they could be used as chemopreventive or anticancer agents.

Anticancer Res. 2007 Jan-Feb;27(1A):357-62

Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.).

Since cancer is the most common cause of death in the world population, the possibility that readily available natural substances from plants, vegetables, herbs, and spices may be beneficial in the prevention of cancer warrants closer examination. Saffron in filaments is the dried, dark red stigmata of Crocus sativus L. flowers and it is used as a spice, food colorant, and a drug in medicine. A growing body of research has demonstrated that saffron extract itself and its main constituents, the carotenoids, possess chemopreventive properties against cancer. This review discusses recent literature data and our results on the cancer chemopreventive activities of saffron and its main ingredients.

Exp Biol Med (Maywood). 2002 Jan;227(1):20-5

Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents.

Radical scavenging activity is involved in aging processes, antiinflammatory, anticancer and wound healing activity. Hence, in the present study the DPPH radical scavenging activity of a natural product that possesses biological properties, an extract of Crocus sativus L. (saffron), grown in Crocos, Kozani (Greece), and some of its bioactive constituents (crocin, safranal) was studied. It was shown that a methanol extract of Crocus sativus exhibited high antioxidant activity, although it contains several active and inactive constituents. In trying to approximate a structure-activity relationship, two bioactive constituents of saffron extract were tested, namely crocin and safranal. Crocin showed high radical scavenging activity (50% and 65% for 500 and 1,000 ppm solution in methanol, respectively), followed by safranal (34% for 500 ppm solution). All the tested samples showed high radical scavenging activity, probably due to the ability to donate a hydrogen atom to the DPPH radical.Thus, saffron grown in Greece can be used promisingly in functional foods, drinks with antioxidant activity, in pharmaceutical and cosmetic preparations for their antioxidant activity and probably for their antiaging activity. Saffron can also be used internally in the form of powder or other pharmacotechnical formulae as a food supplement with antioxidant properties.

Phytother Res. 2005 Nov;19(11):997-1000

Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity.

Crocetin is a carotenoid that is the aglicone of crocin, which are found in saffron stigmas (Crocus sativus L.) and gardenia fruit (Gardenia jasminoides Ellis). In this study, we investigated the effects of crocetin on retinal damage. To examine whether crocetin affects stress pathways, we investigated intracellular oxidation induced by reactive oxygen species, expression of endoplasmic reticulum (ER) stress-related proteins, disruption of the mitochondrial membrane potential ((m)), and caspases activation. In vitro, we employed cultured retinal ganglion cells (RGC-5, a mouse ganglion cell-line transformed using E1A virus). Cell damage was induced by tunicamycin or hydrogen peroxide (H(2)O(2)) exposure. Crocetin at a concentration of 3μM showed the inhibitory effect of 50-60% against tunicamycin- and H(2)O(2)-induced cell death and inhibited increase in caspase-3 and -9 activity. Moreover, crocetin inhibited the enzymatic activity of caspase-9 in a cell-free system. In vivo, retinal damage in mice was induced by exposure to white light at 8000lx for 3h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5days after light exposure and recording the electroretinogram (ERG). Retinal cell damage was also detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at 48h after light exposure. Crocetin at 100mg/kg, p.o. significantly inhibited photoreceptor degeneration and retinal dysfunction and halved the expression of TUNEL-positive cells. These results indicate that crocetin has protective effects against retinal damage in vitro and in vivo, suggesting that the mechanism may inhibit increase in caspase-3 and -9 activities after retinal damage.

Eur J Pharmacol. 2011 Jan 10;650(1):110-9

Antidepressant properties of bioactive fractions from the extract of Crocus sativus L.

The aim of this study was to investigate the antidepressant properties of stigmas and corms of Crocus sativus L. The aqueous ethanol extract of C. sativus corms was fractionated on the basis of polarity. Among the different fractions, the petroleum ether fraction and dichloromethane fraction at doses of 150, 300, and 600 mg/kg showed significant antidepressant-like activities in dose-dependent manners, by means of behavioral models of depression. The immobility time in the forced swimming test and tail suspending test was significantly reduced by the two fractions, without accompanying changes in ambulation when assessed in the open-field test. By means of a gas chromatography-mass spectrometry technique, twelve compounds of the petroleum ether fraction were identified. These data show that administration of C. sativus corms extract produces antidepressant-like effects. Aqueous stigmas extract also exerted antidepressive effects in the behavioral models. Crocin 1 and crocin 2 of the aqueous stigmas extract were identified by a reversed-phase HPLC analysis. In addition, the bioactive compound crocin 1 in this herb was quantitatively determined. The data indicate that antidepressant-like properties of aqueous stigma extracts may be due to crocin 1, giving support to the validity of the use of this plant in traditional medicine. All these results suggest that the low polarity parts of C. sativus corms should be considered as a new plant material for curing depression, which merit further studies regarding antidepressive-like activities of chemical compounds isolated from the two fractions and mechanism of action.

J Nat Med. 2010 Jan;64(1):24-30

Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration.

PURPOSE: To evaluate the functional effect of short-term supplementation of saffron, a spice containing the antioxidant carotenoids crocin and crocetin, in early age-related macular degeneration (AMD). METHODS: Twenty-five patients with AMD were randomly assigned to oral saffron 20 mg/d or placebo supplementation over a 3-month period and then reverted to placebo or saffron for a further 3 months. Focal electroretinograms (fERGs) and clinical findings were recorded at baseline and after 3 months of saffron or placebo supplementation. fERGs were recorded in response to a sinusoidally modulated (41 Hz), uniform field presented to the macular region (18°) at different modulations between 16.5% and 93.5%. Main outcome measures were fERG amplitude (in microvolts), phase (in degrees), and modulation thresholds. RESULTS: After saffron, patients' fERGs were increased in amplitude, compared with either baseline or values found after placebo supplementation (mean change after saffron, 0.25 log μV; mean change after placebo, -0.003 log μV; P < 0.01). fERG thresholds were decreased after saffron supplementation but not placebo, compared with baseline (mean change after saffron, -0.26 log units; mean change after placebo, 0.0003 log units). CONCLUSIONS: The results indicate that short-term saffron supplementation improves retinal flicker sensitivity in early AMD. Although the results must be further replicated and the clinical significance is yet to be evaluated, they provide important clues that nutritional carotenoids may affect AMD in novel and unexpected ways, possibly beyond their antioxidant properties. ( number, NCT00951288.).

Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6118-24