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(n°500) Safranal, a Saffron Constituent, Attenuates Retinal Degeneration in P23H Rats

Fernández-Sánchez L, Lax P, Esquiva G, Martín-Nieto J, Pinilla I, Cuenca N., PLoS One. 2012;7(8):e43074. Epub 2012 Aug 10., University of Alicante, Alicante, Spain.


Saffron, an extract from Crocus sativus, has been largely used in traditional medicine for its antiapoptotic and anticarcinogenic properties. In this work, we investigate the effects of safranal, a component of saffron stigmas, in attenuating retinal degeneration in the P23H rat model of autosomal dominant retinitis pigmentosa. Our findings indicate that dietary supplementation with safranal slows photoreceptor cell degeneration and ameliorates the loss of retinal function and vascular network disruption in P23H rats. This work also suggests that safranal could be potentially useful to retard retinal degeneration in patients with retinitis pigmentosa.

(n° 501) A Longitudinal Follow-Up Study of Saffron Supplementation in Early Age-Related Macular Degeneration: Sustained Benefits to Central Retinal Function

Piccardi M, Marangoni D, Minnella AM, Savastano MC, Valentini P, Ambrosio L, Capoluongo E, Maccarone R, Bisti S, Falsini B., Evid Based Complement Alternat Med. 2012;2012:429124. Epub 2012 Jul 18., Universita' Cattolica del Sacro Cuore, Roma, Italy.


Objectives. In a previous randomized clinical trial (Falsini et al. (2010)), it was shown that short-term Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD). The aim of this study was to evaluate whether the observed functional benefits from Saffron supplementation may extend over a longer follow-up duration. . Conclusion. These results indicate that in early AMD Saffron supplementation induces macular function improvements from baseline that are extended over a long-term follow up.

(n° 502) Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity.

Yamauchi M, Tsuruma K, Imai S, Nakanishi T, Umigai N, Shimazawa M, Hara H., Eur J Pharmacol. 2011 Jan 10;650(1):110-9. Epub 2010 Oct 14., Gifu Pharmaceutical University, Gifu, Japan.


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. 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.

(n° 503) Oral administration of crocetin prevents inner retinal damage induced by N-methyl-d-aspartate in mice

Ohno Y, Nakanishi T, Umigai N, Tsuruma K, Shimazawa M, Hara H., Eur J Pharmacol. 2012 Sep 5;690(1-3):84-9. Epub 2012 Jul 1., Gifu Pharmaceutical University, Gifu , Japan..


Crocetin, an aglycone of crocin, is found in stigmas of the saffron crocus (Crocus starus L.) and has been used in traditional medicine. We investigated the effects of oral administration of crocetin on damage induced by N-methyl-d-aspartate (NMDA) in the murine retina. Crocetin was orally administered before and after intravitreal injection of NMDA. A. These findings indicate that oral administration of crocetin prevented NMDA-induced retinal damage via inhibition of the caspase pathway.

(n° 504) Crocin "saffron" protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes.

El-Beshbishy HA, Hassan MH, Aly HA, Doghish AS, Alghaithy AA., Ecotoxicol Environ Saf. 2012 Sep;83:47-54. Epub 2012 Jul 4., Taibah University, Madinah, Saudi Arabia; and Al-Azhar University, Nasr City, Cairo Egypt.


Beryllium chloride (BeCl(2)) is a highly toxic substance that accumulates in different tissues after absorption. The purpose of this study was to investigate protective role of crocin against BeCl(2)-intoxication in rats. Our results suggested that, BeCl(2) induced oxidation of cellular lipids and proteins and that administration of crocin reduced BeCl(2)-induced oxidative stress combined with initiation of mRNA expression of antioxidant genes.

(n° 505) Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of alpha-tocopherol.

Ochiai T, Ohno S, Soeda S, Tanaka H, Shoyama Y, Shimeno H., Neurosci Lett. 2004 May 13;362(1):61-4., Fukuoka University, Fukuoka 814-180, Japan


Crocin is a pharmacologically active component of Crocus sativus L. (saffron) used in traditional Chinese medicine. We report here the effects of crocin on neuronally differentiated pheochromocytoma (PC-12) cells deprived of serum/glucose. These antioxidant effects of crocin were more effective than those of alpha-tocopherol at the same concentration. Crocin also suppressed the activation of caspase-8 caused by serum/glucose deprivation. These results together with our previous data suggest that crocin is a unique and potent antioxidant that combats oxidative stress in neurons.

(n° 506) Effect of Saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats.

Saleem S, Ahmad M, Ahmad AS, Yousuf S, Ansari MA, Khan MB, Ishrat T, Islam F., J Med Food. 2006 Summer;9(2):246-53., Jamia Hamdard University, New Delhi, India


The modifying effects of Crocus sativus (CS) stigma extract on neurobehavioral activities, malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase (SOD), catalase (CAT), and Na(+),K(+)-ATPase activities, and glutamate (Glu) and aspartate (Asp) content were examined in the middle cerebral artery (MCA) occlusion (MCAO) model of acute cerebral ischemia in rats. The present results may suggest the effectiveness of CS in focal ischemia most probably by virtue of its antioxidant property.

(n° 507) Inhibition of human platelet aggregation and membrane lipid peroxidation by food spice, saffron.

Jessie SW, Krishnakantha TP., Mol Cell Biochem. 2005 Oct;278(1-2):59-63., Central Food Technological Research Institute, Mysore, India.


The inhibitory activity of saffron extract was studied on human platelets. Platelet aggregation and lipid peroxidation were evaluated with platelet rich plasma (PRP) and platelet membranes respectively obtained from blood of healthy human volunteers. Lipid peroxidation in platelet membranes induced by iron-ascorbic acid system was inhibited by saffron extract significantly with IC50 of 0.33 mg. Hence, it may be said that aqueous extract of saffron may have component(s), which protect platelets from aggregation and lipid peroxidation.

(n° 508) Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup.

Shati AA, Elsaid FG, Hafez EE., Neuroscience. 2011 Feb 23;175:66-74. Epub 2010 Nov 27., King Khalid University, Abha , Saudi Arabia.


Aluminium has been proposed as an environmental factor that may affect several enzymes and other biomolecules related to neurotoxicity and Alzheimer's disease (AD). The promising protective effect of aqueous saffron extract and honey syrup on neurotoxicity induced by aluminuim chloride (AlCl(3)) may be derived from their own antioxidant properties. We conclude that the biochemical and molecular studies showed the neurotoxicity of AlCl(3) in the brains of mice. In addition, there was an ameliorative change with saffron extract and honey syrup against AlCl(3) neurotoxicity. The obtained molecular results suggest that AlCl(3) made induction for BCL-W gene, which is an anticancer gene or belongs to the DNA repair system in the brain cells, as well as for R-spondin and inositol polyphosphate 4-phosphatase genes, which help in cell proliferation.

(n° 509) Saffron (Crocus sativus) aqueous extract and its constituent crocin reduces stress-induced anorexia in mice.

Halataei BA, Khosravi M, Arbabian S, Sahraei H, Golmanesh L, Zardooz H, Jalili C, Ghoshooni H., Phytother Res. 2011 Dec;25(12):1833-8. doi: 10.1002/ptr.3495. Epub 2011 Apr 19., Islamic AZAD University, North Tehran Branch, Tehran, Iran


In the present study, the effects of an ethanol and aqueous extract of saffron Crocus sativus and its constituents safranal and crocin on the stress-induced reduction in food intake, weight gain and anorexic time in mice were investigated. It can be concluded that the saffron aqueous extract and its constituent crocin reduce side effects of electroshock stress in mice.

(n° 510) Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus.

Hosseinzadeh H, Sadeghnia HR. J Pharm Pharm Sci. 2005 Aug 22;8(3):394-9., Mashhad University of Medical Sciences, Mashhad, Iran


Increased oxidative stress has been implicated in the mechanisms of delayed neuronal cell death following cerebral ischemic insult. In this study, we investigated whether safranal, an active constituent of Crocus sativus L. stigmas, may ameliorate ischemia-reperfusion injury (IRI)-induced oxidative damage in rat hippocampus. It is concluded that safranal have some protective effects on different markers of oxidative damage in hippocampal tissue from ischemic rats.

(n° 511) Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells.

Soeda S, Ochiai T, Paopong L, Tanaka H, Shoyama Y, Shimeno H., Life Sci. 2001 Nov 2;69(24):2887-98., Fukuoka University, Japan.


Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-alpha on neuronally differentiated PC-12 cells. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.

(n° 512) A dietary colorant crocin mitigates arthritis and associated secondary complications by modulating cartilage deteriorating enzymes, inflammatory mediators and antioxidant status.

Hemshekhar M, Sebastin Santhosh M, Sunitha K, Thushara RM, Kemparaju K, Rangappa KS, Girish KS., Department of Studies in Biochemistry, University of Mysore, Mysore 06, Karnataka, India., Biochimie. 2012 Dec;94(12):2723-33. doi: 10.1016/j.biochi.2012.08.013. Epub 2012 Aug 24.


Articular cartilage degeneration and inflammation are the hallmark of progressive arthritis and is the leading cause of disability in 10-15% of middle aged individuals across the world. Cartilage and synovium are mainly degraded by either enzymatic or non-enzymatic ways. Matrix metalloproteinases (MMPs), hyaluronidases (HAases) and aggrecanases are the enzymatic mediators and inflammatory cytokines and reactive oxygen species being non-enzymatic mediators. In addition, MMPs and HAases generated end-products act as inflammation inducers via CD44 and TLR-4 receptors involved NF-κB pathway. Although several drugs have been used to treat arthritis, numerous reports describe the side effects of these drugs that may turn fatal. On this account several medicinal plants and their isolated molecules have been involved in modern medicine strategies to fight against arthritis. In view of this, the present study investigated the antiarthritic potentiality of Crocin, a dietary colorant carotenoid isolated from stigma of Crocus sativus. Crocin effectively neutralized the augmented serum levels of enzymatic (MMP-13, MMP-3 and MMP-9 and HAases) and non-enzymatic (TNF-α, IL-1β, NF-κB, IL-6, COX-2, PGE(2) and ROS) inflammatory mediators. Further, Crocin re-established the arthritis altered antioxidant status of the system (GSH, SOD, CAT and GST). It also protected the bone resorption by inhibiting the elevated levels of bone joint exoglycosidases, cathepsin-D and tartrate resistant acid phosphatases. Taken together, Crocin revitalized the arthritis induced cartilage and bone deterioration along with inflammation and oxidative damage that could be accredited to its antioxidant nature. Thus, Crocin could be an effective antiarthritic agent which can equally nullify the arthritis associated secondary complication.

(n° 513) The effect of Crocus sativus extract on human lymphocytes' cytokines and T helper 2/T helper 1 balance.

Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A., J Med Food. 2011 Dec;14(12):1538-45., Mashhad University of Medical Sciences, Mashhad, Iran.


The effects of macerated extracts of Crocus sativus (Family Iridaceae) (saffron) on cell viability and cytokine release of stimulated peripheral blood mononuclear cells by phytohemagglutinin (PHA) and nonstimulated cells were examined. These results indicated that the extract of saffron leads to increased ratio of IFN-γ to IL-4.

(n° 514) Further examination of antiradical properties of Crocus sativus stigmas extract rich in crocins.

Ordoudi SA, Befani CD, Nenadis N, Koliakos GG, Tsimidou MZ., J Agric Food Chem. 2009 Apr 22;57(8):3080-6., Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.


Data for antiradical properties of saffron extract and its bioactive constituents (crocins, crocetin) are limited and poorly discussed in comparison with those of extracts containing potent scavengers. Further examination was sought using the Folin-Ciocalteu (F-C) reagent and various free radical species produced in cell-free or cell model systems. Our findings point out that saffron extracts exhibit a remarkable intracellular antioxidant activity that cannot be revealed using assays repeatedly applied to the evaluation of phenolic-type antioxidants.

(n° 515) Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.

Yoshino F, Yoshida A, Umigai N, Kubo K, Lee MC.,J Clin Biochem Nutr. 2011 Nov;49(3):182-7. Epub 2011 Oct 29., Kanagawa Dental College, 82 Inaoka-cho, Yokosuka, , Japan.


Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain

(n° 516) Phosphorylation arbitrates safranal-induced myocardial protection against ischemia-reperfusion injury in rats.

Bharti S, Golechha M, Kumari S, Siddiqui KM, Arya DS., Eur J Nutr. 2012 Sep;51(6):719-27. Epub 2011 Oct 9., Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India


Traditional medicine has been appropriately identified as the most productive soil for the cultivation and harvesting of modern medicines. Herein, we postulate that safranal, an active constituent of Crocus sativus, owing to its strong antioxidant and anti-apoptotic potential, could be a valuable molecule in alleviating myocardial ischemia-reperfusion (IR) injury. To evaluate this hypothesis, safranal (0.1-0.5 mL/kg/day, i.p.) We concluded that safranal not only significantly decreased infarct size, but also improved left ventricular functions and the overall hemodynamic status of the myocardium. Interestingly, safranal enhanced phosphorylation of Akt/GSK-3β/eNOS and suppressed IKK-β/NF-κB protein expressions in IR-challenged myocardium. Our findings also imply that safranal exhibits strong anti-apoptotic potential, as evidenced by upregulated Bcl-2 expression and downregulated Bax and caspase3 expression with decreased TUNEL positivity. Moreover, safranal dose-dependently normalized myocardial antioxidant and nitrotyrosine levels, cardiac injury markers (LDH and CK-MB), and decreased TNF-α level in IR-insulted myocardium. Histopathological and ultrastructural findings correlated with the functional and biochemical outcomes showing preserved myocardial architecture and decreased inflammatory cells and edema. Taken together, these results provide convincing evidence of safranal as an invaluable molecule in myocardial IR setting probably due to its fortified antioxidant and anti-apoptotic potential.

(n° 517) Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells.

Mehri S, Abnous K, Mousavi SH, Shariaty VM, Hosseinzadeh H., Cell Mol Neurobiol. 2012 Mar;32(2):227-35. Epub 2011 Sep 7., Mashhad University of Medical Sciences, Mashhad, Iran


Acrylamide (ACR) is a potent neurotoxic in human and animal models. In this study, the effect of crocin, main constituent of Crocus sativus L. (Saffron) on ACR-induced cytotoxicity was evaluated using PC12 cells as a suitable in vitro model. T. In conclusion, our results indicated that pretreatment with crocin protected cells from ACR-induced apoptosis partly by inhibition of intracellular ROS production.

(n° 518) The role of crocetin in protection following cerebral contusion and in the enhancement of angiogenesis in rats.

Bie X, Chen Y, Zheng X, Dai H., Fitoterapia. 2011 Oct;82(7):997-1002. Epub 2011 Jun 30., School of Medicine Zhejiang University, Hangzhou, China


The protective role of crocetin following cerebral contusion and its effects on the enhancement of angiogenesis in rats was investigated. Our results demonstrate that the protective effects of crocetin upon brain injury may be related to its ability to inhibit apoptosis at early stages of the injury and its ability to promote angiogenesis at the sub-acute stage.

(n° 519) Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity.

Karimi E, Oskoueian E, Hendra R, Jaafar HZ., Molecules. 2010 Sep 6;15(9):6244-56., Universiti Putra Malaysia (UPM), UPM Serdang, Selangor, Malaysia.


Saffron (Crocus sativus L.) belongs to the Iridaceae family. The stigma of saffron has been widely used as spice, medicinal plant, and food additive in the Mediterranean and Subtropical countries. Recently, attention has been paid to the identification of new sources of safe natural antioxidants for the food industry. The antioxidant activities of spices are mainly attributed to their phenolic and flavonoid compounds. Saffron is one of the spices believed to possess antioxidant properties, but information on its antioxidant activity and phenolic, flavonoids compound are rather limited, therefore this research was carried out to evaluate the antioxidant activity of saffron stigmas extracted with different solvents. In summary, saffron stigmas showed antioxidant activity and methanol appeared to be the best solvent to extract the active components, among which the presence of gallic acid and pyrogallol might contribute towards the stigma's antioxidant properties. Hence, saffron stigma could be applied as a natural antioxidant source for industrial purposes.

(n° 520) The effect of saffron (Crocus sativus) extract for healing of second-degree burn wounds in rats.

Khorasani G, Hosseinimehr SJ, Zamani P, Ghasemi M, Ahmadi A., Keio J Med. 2008 Dec;57(4):190-5, Mazandaran University of Medical Sciences, Iran.


The aim of this study was to evaluate the efficacy of pollen of saffron extract cream in the treatment of thermal induced burn wounds and to compare its results with silver sulfadiazine (SSD) in rats. The wound size of saffron group was significantly smaller than other groups. Histological comparison has shown that saffron significantly increased re-epithelialization in burn wounds, as compared to other cream-treated wounds. Although the exact mechanism of saffron is unclear, anti-inflammatory and antioxidant effects of saffron may have contributed to the wound healing. The results of this study raise the possibility of potential efficacy of saffron in accelerating wound healing in burn injuries.

(n° 521) Saponins from the Spanish saffron Crocus sativus are efficient adjuvants for protein-based vaccines.

Castro-Díaz N, Salaun B, Perret R, Sierro S, Romero JF, Fernández JA, Rubio-Moraga A, Romero P., Vaccine. 2012 Jan 5;30(2):388-97. Epub 2011 Nov 10, University of Castilla-La Mancha, Albacete, Spain


Protein and peptide-based vaccines provide rigorously formulated antigens. However, these purified products are only weakly immunogenic by themselves and therefore require the addition of immunostimulatory components or adjuvants in the vaccine formulation. Various compounds derived from pathogens, minerals or plants, possess pro-inflammatory properties which allow them to act as adjuvants and contribute to the induction of an effective immune response. This preclinical study provides an in depth immunological characterization of a new saponin as a vaccine adjuvant, and encourages its further development for use in vaccine formulations.

(n° 522) Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies.

Geromichalos GD, Lamari FN, Papandreou MA, Trafalis DT, Margarity M, Papageorgiou A, Sinakos Z., J Agric Food Chem. 2012 Jun 20;60(24):6131-8. Epub 2012 Jun 11., Theagenion Cancer Hospital, Thessaloniki, Greece.


Inhibitors of acetylcholine breakdown by acetylcholinesterase (AChE) constitute the main therapeutic modality for Alzheimer's disease. In the search for natural products with inhibitory action on AChE, this study investigated the activity of saffron extract and its constituents by in vitro enzymatic and molecular docking studies. Saffron has been used in traditional medicine against Alzheimer's disease. These results reinforce previous findings about the beneficial action of saffron against Alzheimer's disease and may be of value for the development of novel therapeutic agents based on carotenoid-based dual binding inhibitors.

(n° 523) Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats.

Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA., Phytother Res. 2012 Mar;26(3):381-6. doi: 10.1002/ptr.3566. Epub 2011 Jul 19., Mashhad University of Medical Sciences, Mashhad, Iranal memory after chronic cerebral hypoperfusion in rats.


Cerebral ischemia produces brain damage and related behavioral deficits such as memory. In this study, a rat model of chronic cerebral hypoperfusion was used to determine whether saffron extract and crocin, which are potent antioxidants and free radical scavengers, can reduce vascular cognitive impairment. The results showed that the escape latency time was significantly reduced from 24.64 s in the control group to 8.77 and 10.47 s by crocin (25 mg/kg) and saffron extract (250 mg/kg). The traveled distance to find the platform was also changed from 772 cm in the control group to 251 and 294 cm in the crocin (25 mg/kg) and saffron extract (250 mg/kg) groups. The percentages of time spent in the target quadrant, in comparison with the control group (24.16%), increased to 34.25% in the crocin (25 mg/kg) and 34.85% in the saffron extract (250 mg/kg) group. This study suggests that saffron extract and crocin improve spatial cognitive abilities following chronic cerebral hypoperfusion and that these effects may be related to the antioxidant effects of these compounds.

(n° 524) Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells.

Mousavi SH, Tayarani NZ, Parsaee H.,Mashhad University of Medical Sciences, Mashhad, Iran.


Diabetic neuropathy is one of the most frequent complications of diabetes. Despite some studies, the exact mechanism of glucose neurotoxicity has not been fully elucidated. Increased reactive oxygen species (ROS) has proposed as a possible mechanism. Crocus sativus L. (saffron) has been known as a source of antioxidants. Therefore, neuroprotective effect of saffron extract, its active component crocin and gamma-glutamylcysteinylglycine (GSH) was studied . These results suggest saffron and its carotenoid crocin could be potentially useful in diabetic neuropathy treatment.

(n° 525) Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells.

Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, Jung WS, Cho KH, Park JH, Kang I, Hong JW, Lee EH., Eur J Pharmacol. 2010 Dec 1;648(1-3):110-6. Epub 2010 Sep 18., Kyung Hee University, Yongin-si , South Korea


Microglial cells play critical roles in the immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of microglia helps in restoring CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that observed in Alzheimer's and Parkinson's diseases. Crocin and crocetin, found in the fruits of gardenia and in the stigmas of saffron, have been considered for the treatment of various disorders in traditional oriental medicine. Crocin and crocetin have been reported to have diverse pharmacological functions, such as anti-hyperlipidemic, anti-atherosclerotic, and anti-cancer effects. Specifically, the neuroprotective potential of crocetin derivatives has previously been demonstrated. The specific aim of this study was to examine whether crocin or crocetin represses microglial activation. Crocin and crocetin were shown to be effective in the inhibition of LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells. These compounds reduced the LPS-stimulated productions of tumor necrosis factor-α, interleukin-1β, and intracellular reactive oxygen species. The compounds also effectively reduced LPS-elicited NF-κB activation. In addition, crocin reduced NO release from microglia stimulated with interferon-γ and amyloid-β. In organotypic hippocampal slice cultures, both crocin and crocetin blocked the effect of LPS on hippocampal cell death. These results suggest that crocin and crocetin provide neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.

(n° 526) Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats' memory.

Pitsikas N, Zisopoulou S, Tarantilis PA, Kanakis CD, Polissiou MG, Sakellaridis N., Behav Brain Res. 2007 Nov 2;183(2):141-6. Epub 2007 Jun 12., University of Thessaly, Larissa, Greece


Crocus sativus L. is a plant cultivated in various parts of the world. Its involvement in learning and memory processes has been proposed. Crocins are water-soluble carotenoids and are among the active components of C. sativus L. The present study was designed to investigate in the rat the effects of crocins on recognition and spatial memory. In a first study, crocins (15 and 30mg/kg) counteracted delay-dependent recognition memory deficits in the normal rat, suggesting that these carotenoids modulate storage and/or retrieval of information. In a subsequent study, treatment with crocins (30mg/kg and to a lesser extent also 15mg/kg) attenuated scopolamine (0.2mg/kg)-induced performance deficits in the radial water maze test. The present results support and extend the enhancing effects of crocins on memory and, then, to our knowledge, for the first time, demonstrate its implication in the mechanisms underlying recognition and spatial memory.

(n° 527) Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo.

Ochiai T, Shimeno H, Mishima K, Iwasaki K, Fujiwara M, Tanaka H, Shoyama Y, Toda A, Eyanagi R, Soeda S., Biochim Biophys Acta. 2007 Apr;1770(4):578-84. Epub 2006 Dec 5., Fukuoka University, Fukuoka , Japan


Crocus sativus L. (saffron) has been used as a spice for flavoring and coloring food preparations, and in Chinese traditional medicine as an anodyne or tranquilizer. Our previous study demonstrated that crocin, a carotenoid pigment of saffron, can suppress the serum deprivation-induced death of PC12 cells by increasing glutathione (GSH) synthesis and thus inhibiting neutral sphingomyelinase (nSMase) activity and ceramide formation. The carotenoid pigments of saffron consist of crocetin di-(beta-d-glucosyl)-ester [dicrocin], crocetin-(beta-d-gentiobiosyl)-(beta-d-glucosyl)-ester [tricrocin] and crocetin-di-(beta-d-gentiobiosyl)-ester [crocin]. Saffron also contains picrocrocin, the substance causing saffron's bitter taste. In this study, to confirm whether neuroprotective effects of saffron are caused solely by crocin, we examined the antioxidant and GSH-synthetic activities of these crocins in PC12 cells under serum-free and hypoxic conditions. Measurements of cell viability, peroxidized membrane lipids and caspase-3 activity showed that the rank order of the neuroprotective potency at a concentration of 10 muM was crocin>tricrocin>dicrocin and picrocrocin (the latter two crocins had a little or no potency). In addition, we show that among these saffron's constituents, crocin most effectively promotes mRNA expression of gamma-glutamylcysteinyl synthase (gamma-GCS), which contributes to GSH synthesis as the rate-limiting enzyme, and that the carotenoid can significantly reduce infarcted areas caused by occlusion of the middle cerebral artery (MCA) in mice.

(n° 528) Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection.

Papandreou MA, Tsachaki M, Efthimiopoulos S, Cordopatis P, Lamari FN, Margarity M., Behav Brain Res. 2011 Jun 1;219(2):197-204. Epub 2011 Jan 14., University of Patras, Patras, Greece


Brain aging is characterized by cognitive decline and memory deficits that could be the result of oxidative stress and impaired cholinergic function. In this study, the effects of a daily, 7-day, intraperitoneal administration of saffron on cognitive functions were examined in both healthy adult (4 months old) and aged (20 months old), male Balb-c mice (n=8/group), by passive avoidance test. These data, together with earlier studies suggest that crocetin is a unique and potent antioxidant, capable of mediating the in vivo effects of saffron.

(n° 529) Crocin improved learning and memory impairments in streptozotocin-induced diabetic rats.

Tamaddonfard E, Farshid AA, Asri-Rezaee S, Javadi S, Khosravi V, Rahman B, Mirfakhraee Z., Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran., Iran J Basic Med Sci. 2013 Jan;16(1):91-100.


Objective(s): Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP) injection of streptozotocin (STZ, 45 mg/kg). Transfer latency (TL) paradigm in elevated plus-maze (EPM) was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1) and retention transfer latency (TL2), and MDA, decreased transfer latency shortening (TLs) and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.

(n° 530) Crocetin attenuates spatial learning dysfunction and hippocampal injury in a model of vascular dementia

Tashakori-Sabzevar F, Hosseinzadeh H, Motamedshariaty VS, Movassaghi AR, Mohajeri SA., Curr Neurovasc Res. 2013 Nov;10(4):325-34., Pharmaceutical Research Center, School of pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.


Chronic cerebral hypoperfusion produces brain ischemia and is associated with related memory impairment. In this study, we prepared crocetin from crocin (the main water soluble pigment in saffron stigmas) in an acidic hydrolysis and its purity was evaluated using spectrophotometry, thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The memory enhancing effect of crocetin was then studied in a rat model of chronic cerebral hypoperfusion. Different doses of crocetin were administered intraperitoneally (i.p.). The spatial learning and memory function were tested using Morris water maze, after permanent occlusion of common carotids. Finally, the animals were euthanatized in CO2 chamber and histopathological changes in cerebral cortex and hippocampus were investigated. The results indicated that the escape latency time significantly decreased in crocetin treated rats, in comparison with control animals. Also, the percentage of time spent and traveled distance in target quadrant on final test trial day increased in crocetin 8 mg/kg group, compared to control group, while no difference was observed between groups in swimming speed. All behavioral results were confirmed by histopathological analysis. According to our data, crocetin (8 mg/kg) could properly protect cerebrocortical and hippocampus neurons against ischemia. In conclusion, treatment with crocetin could effectively prevent neuropathological alterations in hippocampus thereby resulting in improvement of spatial learning memory in rats after chronic cerebral hypoperfusion.

(n° 531) The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines.

Bajbouj K, Schulze-Luehrmann J, Diermeier S, Amin A, Schneider-Stock R., BMC Complement Altern Med. 2012 May 28;12(1):69,


Saffron extract, a natural product, has been shown to induce apoptosis in several tumor cell lines. Nevertheless, the p53-dependency of saffron's mechanism of action in colon cancer remains unexplored. This is the first study showing the effect of saffron in HCT116 colorectal cancer cells with different p53 status. Saffron induced DNA-damage and apoptosis in both cell lines

(n° 532) Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro.

Escribano J, Alonso GL, Coca-Prados M, Fernandez JA., Cancer Lett. 1996 Feb 27;100(1-2):23-30, Universidad de Castilla-La Mancha, Albacete, Spain


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.

(n° 533) Crocetin: an agent derived from saffron for prevention and therapy for cancer.

Gutheil WG, Reed G, Ray A, Anant S, Dhar A., Curr Pharm Biotechnol. 2012 Jan;13(1):173-9., University of Missouri-Kansas City, MO, USA.


Cancer is one of the leading causes of death in the United States and accounts for approximately 8 million deaths per year worldwide. Although there is an increasing number of therapeutic options available for patients with cancer, their efficacy is time-limited and non-curative. Approximately 50-60% cancer patients in the United States utilize agents derived from different parts of plants or nutrients (complementary and alternative medicine), exclusively or concurrently with traditional therapeutic regime such as chemotherapy and/or radiation therapy. The need for new drugs has prompted studies evaluating possible anti-cancer agents in fruits, vegetables, herbs and spices. Saffron, a spice and a food colorant present in the dry stigmas of the plant Crocus sativus L., has been used as an herbal remedy for various ailments including cancer by the ancient Arabian, Indian and Chinese cultures. Crocetin, an important carotenoid constituent of saffron, has shown significant potential as an anti-tumor agent in animal models and cell culture systems. Crocetin affects the growth of cancer cells by inhibiting nucleic acid synthesis, enhancing anti-oxidative system, inducing apoptosis and hindering growth factor signaling pathways. This review discusses the studies on cancer.

(n° 534) Cytotoxic effect of saffron stigma aqueous extract on human transitional cell carcinoma and mouse fibroblast.

Feizzadeh B, Afshari JT, Rakhshandeh H, Rahimi A, Brook A, Doosti H., Urol J. 2008 Summer;5(3):161-7. Source: Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran


Saffron has been suggested to have inhibitory effects on tumoral cells. We evaluated the cytotoxic effect of aqueous extract of saffron on human transitional cell carcinoma (TCC) and mouse non-neoplastic fibroblast cell lines. However, significant growth inhibitory effects of the extract were shown at concentrations of 400 microg/mL and 800 microg/mL. Saffron aqueous extract has inhibitory effects on the growth of both TCC 5637 and normal L929 cell lines. This effect is dose dependent.

(n° 535) Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies.

Magesh V, Singh JP, Selvendiran K, Ekambaram G, Sakthisekaran D., Mol Cell Biochem. 2006 Jul;287(1-2):127-35. Epub 2006 May 10., , University of Madras, Chennai, India


Lung cancer is the leading cause of cancer related mortality worldwide. Crocetin, saffron plant derivative known to play a role in cancer chemoprevention. In the present study the effects of crocetin was tested against lung cancer-bearing mice in both pre-initiation and post-initiation periods.Crocetin profoundly reverted back the pathological changes observed in cancerous animals. From the results crocetin proves to scavenge free radical and plays an important role in cellular function. Tumor incidence and histopathological studies proves crocetin is a potent antitumour agent.

(n° 536) Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice.

Premkumar K, Thirunavukkarasu C, Abraham SK, Santhiya ST, Ramesh A., Hum Exp Toxicol. 2006 Feb;25(2):79-84., University of Madras, Chennai, India


The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and anti-tumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin-C (MMC)--using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.

(n° 537) Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells.

Aung HH, Wang CZ, Ni M, Fishbein A, Mehendale SR, Xie JT, Shoyama CY, Yuan CS., Exp Oncol. 2007 Sep;29(3):175-80., , The Pritzker School of Medicine, University of Chicago, USA


To investigate the anti-proliferative effects of Crocus sativus extract and its major constituent, crocin, on three colorectal cancer cell lines (HCT-116, SW-480, and HT-29). The cell growth inhibition effect was compared to that of non-small cell lung cancer (NSCLC) cells. In addition, Crocus sativus' effect on non-cancer cells was evaluated. The observed effects suggest that crocin is a major responsible constituent in the extract. Significant anti-proliferative effects were also observed in non-small cell lung cancer cells. However, Crocus sativus extract did not significantly affect the growth of non-cancer young adult mouse colon cells. Conclusion: Data from this study demonstrated that Crocus sativus extract and its major constituent, crocin, significantly inhibited the growth of colorectal cancer cells while not affecting normal cells.

(n° 538) Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice.

Das I, Chakrabarty RN, Das S.,Asian Pac J Cancer Prev. 2004 Jan-Mar;5(1):70-6.Chittaranjan National Cancer Institute, Kolkata, India


One of the most promising strategies for cancer prevention today is chemoprevention using readily available natural substances from vegetables, fruits, herbs and spices. Among the spices, saffron (Crocus sativus, L) a member of the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacological studies have demonstrated many health promoting properties including radical scavenging, anti-mutagenic and immuno-modulating effects. In the present study the effects of an aqueous infusion of saffron on two stage skin papillogenesis / carcinogenesis in mice Significant reduction in papilloma formation was found with saffron application in the pre-initiation and post-initiation periods, and particular when the agent was given both pre- and post-initiation. The inhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymes like glutathione-S-transferase (GST) and glutahinoe peroxidase (GPx), as well as catalase (CAT) and superoxide dismutase (SOD).

(n° 539) Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines.

Yamauchi M, Tsuruma K, Imai S, Nakanishi T, Umigai N, Shimazawa M, Hara H., Eur J Pharmacol. 2011 Jan 10;650(1):110-9. Epub 2010 Oct 14., Gifu Pharmaceutical University, Gifu, Japan.


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. 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.

(n° 540) Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma.

Amin A, Hamza AA, Bajbouj K, Ashraf SS, Daoud S., Hepatology. 2011 Sep 2;54(3):857-67. doi: 10.1002/hep.24433. Epub 2011 Jul 19., United Arab Emirates University, Al Ain, United Arab Emirates


Saffron has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of saffron against diethylnitrosamine (DEN)-induced liver cancer in rats. Administration of saffron at doses of 75, 150, and 300 mg/kg/day was started 2 weeks prior to the DEN injection and was continued for 22 weeks. Conclusion: This study provides evidence that saffron exerts a significant chemopreventive effect against liver cancer through inhibition of cell proliferation and induction of apoptosis. This report also shows some evidence that saffron protects rat liver from cancer via modulating oxidative damage and suppressing inflammatory response.

(n° 541) Suppression of pulmonary tumor promotion and induction of apoptosis by Crocus sativus L. extraction.

Samarghandian S, Tavakkol Afshari J, Davoodi S., Appl Biochem Biotechnol. 2011 May;164(2):238-47. Epub 2010 Dec 12., Mashhad University Medical Sciences, Mashhad, Iran.


Saffron is harvested from the dried, dark red stigmas of Crocus sativus flowers. It is used as a spice for flavoring and coloring food as a perfume. It is often used for treating several diseases. We investigated the potential of the ethanolic extract of saffron to induce antiproliferative and cytotoxic effects in cultured carcinomic human alveolar basal epithelial cells in comparison with non-malignant (L929) cells. The results showed that the ethanolic extract of saffron decreased cell viability in malignant cells as a concentration and time-dependent manner. We also showed that even higher concentrations of saffron is safe for L929, but the extract exerts pro-apoptotic effects in a lung cancer-derived cell line and could be considered as a potential chemotherapeutic agent in lung cancer.

(n° 542) Convolvulus galaticus, Crocus antalyensis, and Lilium candidum extracts show their antitumor activity through induction of p53-mediated apoptosis on human breast cancer cell line MCF-7 cells.

Tokgun O, Akca H, Mammadov R, Aykurt C, Deniz G., J Med Food. 2012 Aug 16., Pamukkale University , Kınıklı, Denizli, Turkey .


Abstract Conventional and newly emerging treatment procedures such as chemotherapy, catalytic therapy, photodynamic therapy, and radiotherapy have not succeeded in reversing the outcome of cancer diseases to any drastic extent, which has led researchers to investigate alternative treatment options. It has been reported that several members of the Convolvulaceae, Iridaceae, and Liliaceae families have antitumor activity against some tumor cell lines. Here we first report that Convolvulus galaticus, Crocus antalyensis, and Lilium candidum species have cytotoxic activity on human breast cancer cell line MCF-7 cells. Our results indicate that these plant extracts have cytotoxic effects on human breast carcinoma cell line MCF-7 cells and that this cytotoxic effect comes from p53-mediated stimulation of apoptosis.

(n° 543) The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats.

Hosseinzadeh H, Ziaee T, Sadeghi A., Phytomedicine. 2008 Jun;15(6-7):491-5. Epub 2007 Oct 24., Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR Iran.


In this study, the aphrodisiac activities of Crocus sativus stigma aqueous extract and its constituents, safranal and crocin, were evaluated in male rats. The aqueous extract (80, 160 and 320mg/kg body wt.), crocin (100, 200 and 400mg/kg body wt.), safranal (0.1, 0.2 and 0.4ml/kg), sildenafil (60mg/kg body wt., as a positive control) and saline were administered intraperitoneally to male rats. Mounting frequency (MF), intromission frequency (IF), erection frequency (EF), mount latency (ML), intromission latency (IL) and ejaculation latency (EL) were the factors evaluated during the sexual behavior study. Crocin, at all doses, and the extract, especially at doses 160 and 320mg/kg body wt., increased MF, IF and EF behaviors and reduced EL, IL and ML parameters. Safranal did not show aphrodisiac effects. The present study reveals an aphrodisiac activity of saffron aqueous extract and its constituent crocin.

(n° 544) Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: a pilot study.

Shamsa A, Hosseinzadeh H, Molaei M, Shakeri MT, Rajabi O., Phytomedicine. 2009 Aug;16(8):690-3. Epub 2009 May 9., Ghaem Hospital en Mashhad university of medical sciences, Iran.


In this study, the effect of Crocus sativus (saffron) was studied on male erectile dysfunction (ED). Twenty male patients with ED were followed for ten days in which each morning they took a tablet containing 200mg of saffron. After the ten days of taking saffron there was a statistically significant improvement in tip rigidity and tip tumescence as well as base rigidity and base tumescence. Saffron showed a positive effect on sexual function with increased number and duration of erectile events seen in patients with ED even only after taking it for ten days.

(n° 545) Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial.

Modabbernia A, Sohrabi H, Nasehi AA, Raisi F, Saroukhani S, Jamshidi A, Tabrizi M, Ashrafi M, Akhondzadeh S., Psychopharmacology (Berl). 2012 May 3. , Tehran University of Medical Sciences, Tehran,Iran.


Saffron (Crocus sativus L.) has shown aphrodisiac effects in some animal and human studies. Nine patients (60%) in the saffron group and one patient (7%) in the placebo group achieved normal erectile function (score > 25 on erectile function domain) at the end of the study (P value of Fisher's exact test = 0.005). Frequency of side effects were similar between the two groups. Saffron is a tolerable and efficacious treatment for fluoxetine-related erectile dysfunction One of the great ironies of depression treatment is that while depression can rob you of your desire for sex, the drugs that treat it can be much worse, causing not only low libido, but also erectile dysfunction and difficulties with orgasm.

(n° 546) Effect of saffron on semen parameters of infertile men.

Heidary M, Vahhabi S, Reza Nejadi J, Delfan B, Birjandi M, Kaviani H, Givrad S.,Urol J. 2008 Fall;5(4):255-9., Department of Urology, Lorestan University of Medical Sciences, Khorramabad, Iran.


We conducted this study to determine the effects of saffron (Crocus sativus) on the results of semen analysis in men with idiopathic infertility. In this clinical trial, 52 nonsmoker infertile men whose problem could not be solved surgically were enrolled. They were treated by saffron for 3 months. Saffron, 50 mg, was solved in drinking milk and administered 3 times a week during the study course. Semen analysis was done before and after the treatment and the results were compared. Saffron, as an antioxidant, is positively effective on sperm morphology and motility in infertile men, while it does not increase sperm count.

(n° 547) Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats.

Amin B, Hosseinzadeh H., Fitoterapia. 2012 Jul;83(5):888-95. Epub 2012 Mar 28., Isfahan University of Medical Sciences, Isfahan, Iran.


The current study was designed to evaluate therapeutic potential of systemically administered ethanolic and aqueous extracts of saffron as well as its bioactive ingredients, safranal and crocin, in chronic constriction injury (CCI)-induced neuropathic pain in rats. T In conclusion, the results of this study suggest that ethanolic and aqueous extracts of saffron as well as safranal could be useful in treatment of different kinds of neuropathic pains and as an adjuvant to conventional medicines.

(n° 548) Preventive effect of crocin in inflamed animals and in LPS-challenged RAW 264.7 cells.

Xu GL, Li G, Ma HP, Zhong H, Liu F, Ao GZ., J Agric Food Chem. 2009 Sep 23;57(18):8325-30.


Gardenia jasminoides Ellis and Crocus sativus L. are both traditional Chinese medicines that have significant biologic activities on inflammatory processes. But the active ingredients remain unclear. Crocin, a representative of carotenoid compounds, has now drawn considerable attention not only because it is a natural food colorant but also because it has great potential in medicine. But until now, the systematic anti-inflammatory effect of crocin has not been well established. In the present study, experiments were carried out to evaluate the anti-inflammatory effects of crocin in vitro and in vivo. In vitro, cyclooxygenase (COX) inhibition assays showed that crocin exhibits a dual inhibitory activity against the COX-1 and COX-2 enzymes. Anti-inflammatory activity in vivo was evaluated using two animal edema model tests. Pretreatment with crocin (p.o.) dose-dependently inhibited the xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. In gastric lesion tests, crocin was gastric-sparing in that it elicited markedly fewer stomach lesions as compared to the number of stomach lesions caused by indomethacin in rats. In further studies, crocin was found to significantly inhibit the productions of prostaglandin E(2) (PGE(2)) in lipopolysaccharide (LPS)-challenged RAW 264.7, which is parallel to its prevention of the nuclear translocation of the NF-kappaB p50 and p65 subunits. These data indicate that crocin exhibits obvious anti-inflammatory effects and may be one of the active ingredients in Gardenia jasminoides Ellis or Crocus sativus L. that can modulate inflammatory processes.

(n° 549) The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs.

Boskabady MH, Tabatabaee A, Byrami G.,Phytomedicine. 2012 Jul 15;19(10):904-11. Epub 2012 Jun 27., Mashhad University of Medical Sciences, Mashhad, Iran.


Different pharmacological effects of Crocus sativus have been demonstrated on guinea pig tracheal chains in previous studies. In the present study, the prophylactic effect of the extract of C. sativus and its constituent, safranal on lung pathology and total and differential white blood cells (WBC) of sensitized guinea pigs was examined. These results showed a preventive effect of the extract of C. sativus and its constituent safranal on lung inflammation of sensitized guinea pigs. The results also showed that the effect of the plant is perhaps due to its constituent safranal

(n° 550) Antidepressant properties of bioactive fractions from the extract of Crocus sativus L.

Wang Y, Han T, Zhu Y, Zheng CJ, Ming QL, Rahman K, Qin LP., J Nat Med. 2010 Jan;64(1):24-30. Epub 2009 Sep 29.


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.

(n° 551) Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial.

Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S., Phytomedicine. 2006 Nov;13(9-10):607-11. Epub 2006 Sep 18., Arak University of Medical Sciences, Arak Tehran, Iran


Depression is a major worldwide health problem. Indeed, by 2020, depressive disorders are estimated to represent the second largest disease burden worldwide. Although a variety of pharmaceutical agents are available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. Our objective was to assess the efficacy of petal of Crocus sativus in the treatment of mild-to-moderate depression in a 6-week double-blind, placebo-controlled and randomized trial. The results of this study indicate the efficacy of petal of C. sativus in the treatment of mild-to-moderate depression.

(n° 552) Reduction of metabolic and behavioral signs of acute stress in male Wistar rats by saffron water extract and its constituent safranal.

Hooshmandi Z, Rohani AH, Eidi A, Fatahi Z, Golmanesh L, Sahraei H.,Pharm Biol. 2011 Sep;49(9):947-54. Epub 2011 May 19., Islamic AZAD University, Tehran, Iran.


Saffron extract can inhibit the metabolic disorders induced by stress but the mechanism of action of saffron extract in the central nervous system is not clear. The present research investigated the effects of saffron water extract and its constituent, safranal on the behavioral and metabolic signs induced by electroshock stress in male Wistar rats (W: 250-300 g). Dried saffron material and maceration method was used for extraction. The result showed that stress elevated the corticosterone plasma (115 nmol/L) concentration in the control and intra-amygdala (1, 5, and 10 µg/rat)-treated groups but not in groups that received extract or safranal (55 nmol/L) intraperitoneally (1, 5, and 10 mg/kg). Moreover, anorexia was reduced only in groups that received the extract (1, 5, and 10 mg/kg) or safranal (1, 5, and 10 mg/kg) intraperitoneally (50 sec). Stress increased sniffing, rearing, locomotion, and coping time, which were decreased by intraperitoneal (1, 5, and 10 mg/kg) but not by intra-amygdala (1, 5, and 10 µg/rat) administration of saffron extract and safranal.The results revealed that saffron water extract and safranal had an important impact on the reduction of both metabolic and behavioral signs of stress in male Wistar rats. Moreover, the involvement of the amygdala in this observation can be ruled out.

(n° 553) Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review.

Dwyer AV, Whitten DL, Hawrelak JA., Altern Med Rev. 2011 Mar;16(1):40-9., Goulds Naturopathica, Australia


To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints. Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located. Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo. A number of herbal medicines show promise in the management of mild-to-moderate depression.

(n° 554) Safranal enhances non-rapid eye movement sleep in pentobarbital-treated mice.

Liu Z, Xu XH, Liu TY, Hong ZY, Urade Y, Huang ZL, Qu WM., CNS Neurosci Ther. 2012 Aug;18(8):623-30. doi: 10.1111/j.1755-5949.2012.00334.x. Epub 2012 May 28., Fudan University, Shanghai, China , Wannan Medical College, Wuhu, China, saka Bioscience Institute, Osaka, Japan.


Aims: Safranal (2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde, C(10) H(14) O) is an active ingredient in the saffron, which is used in traditional medicine. It has been reported to have sedative and anti-epileptic effects, but its hypnotic effects remain uncertain. The aim of this study was to evaluate effects of safranal on sleep-wake cycle. Conclusion: These findings indicate that safranal enhances NREM sleep in pentobarbital-treated mice. The hypnotic effects of safranal may be related to the activation of the sleep-promoting neurons in the VLPO and the simultaneous inhibition of the wakefulness-promoting neurons in the TMN, suggesting that safranal may be a hypnotic substance.

(n° 555) Crocin promotes non-rapid eye movement sleep in mice.

Masaki M, Aritake K, Tanaka H, Shoyama Y, Huang ZL, Urade Y., Mol Nutr Food Res. 2012 Feb;56(2):304-8. doi: 10.1002/mnfr.201100181. Epub 2011 Oct 28., Osaka Bioscience Institute, Suita, Osaka, Japan


Crocus sativus L. (saffron) has been traditionally used for the treatment of insomnia and other diseases of the nervous systems. Two carotenoid pigments, crocin and crocetin, are the major components responsible for the various pharmacological activities of C. sativus L. In this study, we examined the sleep-promoting activity of crocin and crocetin by monitoring the locomotor activity and electroencephalogram after administration of these components to mice. Crocin (30 and 100 mg/kg) increased the total time of non-rapid eye movement (non-REM) sleep by 60 and 170%, respectively, during a 4-h period from 20:00 to 24:00 after its intraperitoneal administration at a lights-off time of 20:00. Crocetin (100 mg/kg) also increased the total time of non-REM sleep by 50% after the administration. These compounds did not change the amount of REM sleep or show any adverse effects, such as rebound insomnia, after the induction of sleep.

(n° 556) Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus).

Fukui H, Toyoshima K, Komaki R., Phytomedicine. 2011 Jun 15;18(8-9):726-30. Epub 2011 Jan 15., Nara University of Education, Nara, Japan


The purpose of this study was to clarify the effects of saffron odor on symptoms unique to women, such as premenstrual syndrome (PMS), dysmenorrhea (menstrual pain) and irregular menstruation. Thirty-five women with a normal sense of smell were exposed to saffron odor for 20 min. Saliva samples were then collected to measure levels of cortisol (C), testosterone (T) and 17-β estradiol (E) by enzyme immunoassay, and the State-Trait Anxiety Inventory (STAI) was administered as a psychological test.Saffron odor significantly decreased C levels after short-term stimulation (20 min) in both follicular and luteal phases. E level after exposure to saffron odor was increased in both the follicular- and luteal-phase groups. STAI score decreased in the follicular and luteal phases in the saffron group.The present findings support the existence of physiological and psychological effects of saffron odor in women. Our results indicate that saffron odor exert some effects in the treatment of PMS, dysmenorrhea and irregular menstruation. This is the first report to suggest that saffron odor may be effective in treating menstrual distress.

(n° 557) Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial.

Agha-Hosseini M, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara AR, Akhondzadeh S., BJOG. 2008 Mar;115(4):515-9., Tehran University of Medical Sciences, Tehran, Iran.


The aim of this double-blind and placebo-controlled trial was to investigate whether saffron (stigma of Crocus sativus L.) could relieve symptoms of premenstrual syndrome (PMS). Double-blind, randomised and placebo-controlled trial. Women aged 20-45 years with regular menstrual cycles and experience of PMS symptoms for at least 6 months were eligible for the study. Women were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice a day; morning and evening) conclusion : The results of this study indicate the efficacy of C. sativus L. in the treatment of PMS.

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