Saffron

Other Name(s):

Autumn Crocus, Azafrán, Azafron, Croci Stigma, Crocus Cultivé, Crocus sativus, Indian Saffron, Kashmira, Kesar, Kumkuma, Saffron Crocus, Safran, Safran Cultivé, Safran Espagnol, Safran des Indes, Safran Véritable, Spanish Saffron, True Saffron, Zafran.

Overview

Saffron is a plant. The dried stigmas (thread-like parts of the flower) are used to make saffron spice. It can take 75,000 saffron blossoms to produce a single pound of saffron spice. Saffron is largely cultivated and harvested by hand. Due to the amount of labor involved in harvesting, saffron is considered one of the world's most expensive spices. The stigmas are also used to make medicine.

Saffron is used for asthma, cough, whooping cough (pertussis), and to loosen phlegm (as an expectorant). It is also used for sleep problems (insomnia), cancer, “hardening of the arteries” (atherosclerosis), intestinal gas (flatulence), depression, Alzheimer's disease, fright, shock, spitting up blood (hemoptysis), pain, heartburn, and dry skin.

Women use saffron for menstrual cramps and premenstrual syndrome (PMS). Men use it to prevent early orgasm (premature ejaculation) and infertility.

Saffron is also used for to increase interest in sex (as an aphrodisiac) and to induce sweating.

Some people apply saffron directly to the scalp for baldness (alopecia).

In foods, saffron is used as a spice, yellow food coloring, and as a flavoring agent.

In manufacturing, saffron extracts are used as fragrance in perfumes and as a dye for cloth.

How does work?

There isn't enough information to know how saffron might work.

SLIDESHOW

Learn to Spot Depression: Symptoms, Warning Signs, Medication See Slideshow

Uses

Possibly Effective for...

  • Alzheimer's disease. Some research shows that taking a specific saffron product (IMPIRAN, Iran) by mouth for 22 weeks might improve symptoms of Alzheimer's disease about as well as the prescription drug donepezil (Aricept).
  • Depression. Taking specific saffron extracts (Novin Zaferan Co, Iran) by mouth seems to improve symptoms of major depression after 6-8 weeks of treatment. Some studies suggest that saffron might be as effective as taking a low-dose prescription antidepressant such as fluoxetine or imipramine.
  • Menstrual discomfort. Some research shows the taking a specific product containing saffron, anise, and celery seed (SCA, Gol Daro Herbal Medicine Laboratory) reduces pain during the menstrual cycle.
  • Premenstrual syndrome (PMS). Some research shows that taking a specific saffron extract (Department of Cultivation and Development of Institute of Medicinal Plants, Iran) improves symptoms of PMS after two menstrual cycles.

Insufficient Evidence to Rate Effectiveness for...

  • Asthma. Some early research suggests that drinking an herbal tea mixture containing saffron along with anise, black seed, caraway, cardamom, chamomile, fennel, and licorice may reduce asthma symptoms in people with allergic asthma.
  • Athletic performance. Some early research shows that taking a chemical from saffron called crocetin might decrease fatigue in men during exercise.
  • Erectile dysfunction. Some early research suggests that taking saffron might reduce erectile dysfunction and increase the number and duration of erections.
  • Male infertility. Some research suggests that saffron might improve sperm function in men. However, the research has been inconsistent.
  • Psoriasis. Some early research suggests that drinking saffron tea daily, along with a diet rich in fruits and vegetables, might reduce the severity of psoriasis.
  • Insomnia.
  • Cancer.
  • “Hardening of the arteries” (atherosclerosis).
  • Cough.
  • Stomach gas.
  • Early male orgasm (premature ejaculation).
  • Baldness.
  • Pain.
  • Other conditions.
More evidence is needed to rate saffron for these uses.

Side Effects

Saffron is POSSIBLY SAFE for most people when taken by mouth as a medicine for up to 6 weeks. Some possible side effects include dry mouth, anxiety, dizziness, drowsiness, nausea, change in appetite, and headache. Allergic reactions can occur in some people.

Taking large amounts of saffron by mouth is POSSIBLY UNSAFE. High doses can cause poisoning, including yellow appearance of the skin, eyes, and mucous membranes; vomiting; dizziness; bloody diarrhea; bleeding from the nose, lips, and eyelids; numbness; and other serious side effects. Doses of 12-20 grams can cause death.

Special Precautions & Warnings:

Pregnancy and breast-feeding: Taking saffron by mouth in amounts larger than what is normally found in food is LIKELY UNSAFE. Larger amounts of saffron can make the uterus contract and might cause a miscarriage.

Not enough is known about the safety of using saffron during breast-feeding. Stay on the safe side and avoid use.

Bipolar disorder: Saffron seems to be able to affect mood. There is a concern that it might trigger excitability and impulsive behavior (mania) in people with bipolar disorder. Don't use saffron if you have this condition.

Allergies to Lolium, Olea (includes olive), and Salsola plant species: People who are allergic to these plants might also be allergic to saffron.

Heart conditions: Saffron might affect how fast and how strong the heart beats. Taking large amounts of saffron might worsen some heart conditions.

Low blood pressure: Saffron might lower blood pressure. Taking saffron might make blood pressure become too low in people with low blood pressure.

**SpecialPrecautions**

Interactions

Medications for high blood pressure (Antihypertensive drugs)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Saffron might lower blood pressure. Taking saffron along with medications used for lowering high blood pressure might cause your blood pressure to go too low.

Some medications for high blood pressure include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.

Medications for high blood pressure (Calcium channel blockers)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Saffron might lower blood pressure. Taking saffron with medication for high blood pressure might cause your blood pressure to go too low.

Some medications for high blood pressure include nifedipine (Adalat, Procardia), verapamil (Calan, Isoptin, Verelan), diltiazem (Cardizem), isradipine (DynaCirc), felodipine (Plendil), amlodipine (Norvasc), and others.

Dosing

The following doses have been studied in scientific research:

BY MOUTH:

  • For depression: 30 mg/day of a specific saffron extract (Novin Zaferan Co, Iran). A different saffron extract 15 mg twice daily has also been used.
  • For premenstrual syndrome (PMS): 15 mg of a specific ethanol saffron extract twice daily (Department of Cultivation and Development of Institute of Medicinal Plants, Tehran, Iran).
  • For menstrual discomfort: 500 mg of a specific combination product containing saffron, celery seed and anise extracts (SCA, Gol Daro Herbal Medicine Laboratory) taken three times a day for the first three days of menstruation.
  • For Alzheimer's disease: 30 mg/day of a specific saffron product (IMPIRAN, Iran).

QUESTION

Depression is a(n) __________ . See Answer

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to Rate (detailed description of each of the ratings).

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References

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Hosseinzadeh, H. and Noraei, N. B. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother.Res 2009;23(6):768-774. View abstract.

Hosseinzadeh, H. and Sadeghnia, H. R. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: involvement of GABAergic and opioids systems. Phytomedicine. 2007;14(4):256-262. View abstract.

Hosseinzadeh, H. and Sadeghnia, H. R. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci. 2005;8(3):394-399. View abstract.

Hosseinzadeh, H. and Talebzadeh, F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia 2005;76(7-8):722-724. View abstract.

Hosseinzadeh, H. and Younesi, H. M. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC.Pharmacol 3-15-2002;2:7. View abstract.

Hosseinzadeh, H., Abootorabi, A., and Sadeghnia, H. R. Protective effect of Crocus sativus stigma extract and crocin (trans-crocin 4) on methyl methanesulfonate-induced DNA damage in mice organs. DNA Cell Biol. 2008;27(12):657-664. View abstract.

Hosseinzadeh, H., Modaghegh, M. H., and Saffari, Z. Crocus sativus L. (Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid.Based.Complement Alternat.Med. 2009;6(3):343-350. View abstract.

Hosseinzadeh, H., Sadeghnia, H. R., and Rahimi, A. Effect of safranal on extracellular hippocampal levels of glutamate and aspartate during kainic Acid treatment in anesthetized rats. Planta Med. 2008;74(12):1441-1445. View abstract.

Hosseinzadeh, H., Sadeghnia, H. R., Ziaee, T., and Danaee, A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharm Sci. 2005;8(3):387-393. View abstract.

Hosseinzadeh, H., Ziaee, T., and Sadeghi, A. The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats. Phytomedicine. 2008;15(6-7):491-495. View abstract.

Imenshahidi, M., Hosseinzadeh, H., and Javadpour, Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother.Res 12-9-2009; View abstract.

Jagadeeswaran, R., Thirunavukkarasu, C., Gunasekaran, P., Ramamurty, N., and Sakthisekaran, D. In vitro studies on the selective cytotoxic effect of crocetin and quercetin. Fitoterapia 2000;71(4):395-399. View abstract.

Jalali-Heravi, M., Parastar, H., and Ebrahimi-Najafabadi, H. Characterization of volatile components of Iranian saffron using factorial-based response surface modeling of ultrasonic extraction combined with gas chromatography-mass spectrometry analysis. J Chromatogr.A 8-14-2009;1216(33):6088-6097. View abstract.

Jalali-Heravi, M., Parastar, H., and Ebrahimi-Najafabadi, H. Self-modeling curve resolution techniques applied to comparative analysis of volatile components of Iranian saffron from different regions. Anal.Chim.Acta 3-10-2010;662(2):143-154. View abstract.

Jessie, S. W. and Krishnakantha, T. P. Inhibition of human platelet aggregation and membrane lipid peroxidation by food spice, saffron. Mol.Cell Biochem. 2005;278(1-2):59-63. View abstract.

Joukar, S., Najafipour, H., Khaksari, M., Sepehri, G., Shahrokhi, N., Dabiri, S., Gholamhoseinian, A., and Hasanzadeh, S. The effect of saffron consumption on biochemical and histopathological heart indices of rats with myocardial infarction. Cardiovasc.Toxicol 2010;10(1):66-71. View abstract.

Kakehi, K., Kinoshita, M., Oda, Y., and Abdul-Rahman, B. Lectin from bulbs of Crocus sativus recognizing N-linked core glycan: isolation and binding studies using fluorescence polarization. Methods Enzymol. 2003;362:512-522. View abstract.

Kanakis, C. D., Daferera, D. J., Tarantilis, P. A., and Polissiou, M. G. Qualitative determination of volatile compounds and quantitative evaluation of safranal and 4-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde (HTCC) in Greek saffron. J Agric.Food Chem. 7-14-2004;52(14):4515-4521. View abstract.

Kanakis, C. D., Tarantilis, P. A., Pappas, C., Bariyanga, J., Tajmir-Riahi, H. A., and Polissiou, M. G. An overview of structural features of DNA and RNA complexes with saffron compounds: Models and antioxidant activity. J Photochem.Photobiol.B 6-3-2009;95(3):204-212. View abstract.

Kanakis, C. D., Tarantilis, P. A., Tajmir-Riahi, H. A., and Polissiou, M. G. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J Agric.Food Chem. 2-7-2007;55(3):970-977. View abstract.

Kanakis, C. D., Tarantilis, P. A., Tajmir-Riahi, H. A., and Polissiou, M. G. DNA interaction with saffron's secondary metabolites safranal, crocetin, and dimethylcrocetin. DNA Cell Biol. 2007;26(1):63-70. View abstract.

Kandeler, R. and Ullrich, W. R. Symbolism of plants: examples of European-Mediterranean culture presented with biology and history of art. J Exp.Bot. 2009;60(1):6-8. View abstract.

Kanofsky, J. R. and Sima, P. D. Girard's reagent P derivative of beta-Apo-8'-carotenal: a potent photoprotective agent. Photochem.Photobiol. 2001;73(4):349-358. View abstract.

Kazi, H. A. and Qian, Z. Crocetin reduces TNBS-induced experimental colitis in mice by downregulation of NFkB. Saudi J Gastroenterol. 2009;15(3):181-187. View abstract.

Keyhani, E. and Keyhani, J. Comparative study of superoxide dismutase activity assays in Crocus sativus L. corms. Prikl.Biokhim.Mikrobiol. 2006;42(1):111-116. View abstract.

Khalili, M, Roghani, M, and Ekhlasi, M. The Effect of Aqueous Crocus sativus L. Extract on Intracerebroventricular Streptozotocin-induced Cognitive Deficits in Rat: a Behavioral Analysis. Iranian Journal of Pharmaceutical Research 2009;8:185-191.

Khorasani, G., Hosseinimehr, S. J., Zamani, P., Ghasemi, M., and Ahmadi, A. The effect of saffron (Crocus sativus) extract for healing of second-degree burn wounds in rats. Keio J Med. 2008;57(4):190-195. View abstract.

Kim, Y. S., Kim, J. J., Cho, K. H., Jung, W. S., Moon, S. K., Park, E. K., and Kim, D. H. Biotransformation of ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, hesperidin, poncirin, glycyrrhizin, and baicalin by human fecal microflora and its relation to cytotoxicity against tumor cells. J Microbiol.Biotechnol. 2008;18(6):1109-1114. View abstract.

Koyama, A., Ohmori, Y., Fujioka, N., Miyagawa, H., Yamasaki, K., and Kohda, H. Formation of Stigma-Like Structures and Pigment in Cultured Tissues of Crocus sativus. Planta Med. 1988;54(4):375-376. View abstract.

Laabich, A., Vissvesvaran, G. P., Lieu, K. L., Murata, K., McGinn, T. E., Manmoto, C. C., Sinclair, J. R., Karliga, I., Leung, D. W., Fawzi, A., and Kubota, R. Protective effect of crocin against blue light- and white light-mediated photoreceptor cell death in bovine and primate retinal primary cell culture. Invest Ophthalmol.Vis.Sci. 2006;47(7):3156-3163. View abstract.

Leung, Y. K. and Ho, J. W. Effects of vitamins and common drugs on reduction of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rat microsomes. Arch.Physiol Biochem. 2001;109(2):175-179. View abstract.

Li, C. Y. and Wu, T. S. Constituents of the pollen of Crocus sativus L. and their tyrosinase inhibitory activity. Chem.Pharm Bull.(Tokyo) 2002;50(10):1305-1309. View abstract.

Li, C. Y. and Wu, T. S. Constituents of the stigmas of Crocus sativus and their tyrosinase inhibitory activity. J Nat.Prod. 2002;65(10):1452-1456. View abstract.

Li, C. Y., Lee, E. J., and Wu, T. S. Antityrosinase principles and constituents of the petals of Crocus sativus. J Nat.Prod. 2004;67(3):437-440. View abstract.

Li, N., Lin, G., Kwan, Y. W., and Min, Z. D. Simultaneous quantification of five major biologically active ingredients of saffron by high-performance liquid chromatography. J Chromatogr.A 7-23-1999;849(2):349-355. View abstract.

Liakopoulou-Kyriakides, M. and Skubas, A. I. Characterization of the platelet aggregation inducer and inhibitor isolated from Crocus sativus. Biochem.Int. 1990;22(1):103-110. View abstract.

Liu, T. Z. and Qian, Z. Y. [Pharmacokinetics of crocetin in rats]. Yao Xue.Xue.Bao. 2002;37(5):367-369. View abstract.

Liu, Y., Long, Y., Zhu, L., Cao, G., and Zhong, Z. [Physiological and ecological effects of potassium on expansion of crocus corm]. Ying.Yong.Sheng Tai Xue.Bao. 2004;15(4):663-666. View abstract.

Lopez, R. C. and Gomez-Gomez, L. Isolation of a new fungi and wound-induced chitinase class in corms of Crocus sativus. Plant Physiol Biochem. 2009;47(5):426-434. View abstract.

Lucas, C. D., Hallagan, J. B., and Taylor, S. L. The role of natural color additives in food allergy. Adv.Food Nutr.Res 2001;43:195-216. View abstract.

Lv, C. F., Luo, C. L., Ji, H. Y., and Zhao, P. [Influence of crocin on gene expression profile of human bladder cancer cell lines T24]. Zhongguo Zhong.Yao Za Zhi. 2008;33(13):1612-1617. View abstract.

Ma SP, Liu BL. Pharmacological studies of glycosides of saffron crocus (Crocus sativus): effects on blood coagulation, platelet aggregation, and thrombosis. Chinese Traditional and Herbal Drugs (China) 1999;30:196-198.

Maccarone, R., Di Marco, S., and Bisti, S. Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Invest Ophthalmol.Vis.Sci. 2008;49(3):1254-1261. View abstract.

Magesh, V., DurgaBhavani, K., Senthilnathan, P., Rajendran, P., and Sakthisekaran, D. In vivo protective effect of crocetin on benzo(a)pyrene-induced lung cancer in Swiss albino mice. Phytother.Res 2009;23(4):533-539. View abstract.

Magesh, V., Singh, J. P., Selvendiran, K., Ekambaram, G., and Sakthisekaran, D. Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol.Cell Biochem. 2006;287(1-2):127-135. View abstract.

Maggi, L., Carmona, M., Zalacain, A., Tome, M. M., Murcia, M. A., and Alonso, G. L. Parabens as agents for improving crocetin esters' shelf-life in aqueous saffron extracts. Molecules. 2009;14(3):1160-1170. View abstract.

Martin, G., Goh, E., and Neff, A. W. Evaluation of the developmental toxicity of crocetin on Xenopus. Food Chem.Toxicol 2002;40(7):959-964. View abstract.

Martinez, F. V., Munoz Pamplona, M. P., Urzaiz, A. G., and Garcia, E. C. Occupational airborne contact dermatitis from saffron bulbs. Contact Dermatitis 2007;57(4):284-285. View abstract.

Martins, M. L., Martins, H. M., and Bernardo, F. Aflatoxins in spices marketed in Portugal. Food Addit.Contam 2001;18(4):315-319. View abstract.

Mathews-Roth, M. M. Effect of crocetin on experimental skin tumors in hairless mice. Oncology 1982;39(6):362-364. View abstract.

Miyakoshi, J., Tsukada, T., Tachiiri, S., Bandoh, S., Yamaguchi, K., and Takebe, H. Enhanced NOR-1 gene expression by exposure of Chinese hamster cells to high-density 50 Hz magnetic fields. Mol.Cell Biochem. 1998;181(1-2):191-195. View abstract.

Modaghegh, M. H., Shahabian, M., Esmaeili, H. A., Rajbai, O., and Hosseinzadeh, H. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers. Phytomedicine. 2008;15(12):1032-1037. View abstract.

Molnar, J., Szabo, D., Pusztai, R., Mucsi, I., Berek, L., Ocsovszki, I., Kawata, E., and Shoyama, Y. Membrane associated antitumor effects of crocine-, ginsenoside- and cannabinoid derivates. Anticancer Res 2000;20(2A):861-867. View abstract.

Moneret-Vautrin, D. A., Morisset, M., Lemerdy, P., Croizier, A., and Kanny, G. Food allergy and IgE sensitization caused by spices: CICBAA data (based on 589 cases of food allergy). Allerg.Immunol.(Paris) 2002;34(4):135-140. View abstract.

Moraga, A. R., Mozos, A. T., Ahrazem, O., and Gomez-Gomez, L. Cloning and characterization of a glucosyltransferase from Crocus sativus stigmas involved in flavonoid glucosylation. BMC.Plant Biol. 2009;9:109. View abstract.

Moraga, A. R., Nohales, P. F., Perez, J. A., and Gomez-Gomez, L. Glucosylation of the saffron apocarotenoid crocetin by a glucosyltransferase isolated from Crocus sativus stigmas. Planta 2004;219(6):955-966. View abstract.

Moraga, A. R., Rambla, J. L., Ahrazem, O., Granell, A., and Gomez-Gomez, L. Metabolite and target transcript analyses during Crocus sativus stigma development. Phytochemistry 2009;70(8):1009-1016. View abstract.

Morgan, T. J., Venkatesh, B., Crerar-Gilbert, A., Willgoss, D., and Endre, Z. H. Sodium crocetinate does not alter gut hypercapnic responses or renal energy stores during transient sub-diaphragmatic ischaemia. Intensive Care Med. 2003;29(4):652-654. View abstract.

Moshiri, E., Basti, A. A., Noorbala, A. A., Jamshidi, A. H., Hesameddin, Abbasi S., and Akhondzadeh, S. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine. 2006;13(9-10):607-611. View abstract.

Mousavi, S. H., Tavakkol-Afshari, J., Brook, A., and Jafari-Anarkooli, I. Role of caspases and Bax protein in saffron-induced apoptosis in MCF-7 cells. Food Chem.Toxicol 2009;47(8):1909-1913. View abstract.

Mousavi, S. H., Tayarani, N. Z., and Parsaee, H. Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells. Cell Mol.Neurobiol. 2010;30(2):185-191. View abstract.

Naghizadeh, B., Boroushaki, M. T., Vahdati, Mashhadian N., and Mansouri, M. T. Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. Iran Biomed.J 2008;12(2):93-100. View abstract.

Nair, S. C., Kurumboor, S. K., and Hasegawa, J. H. Saffron chemoprevention in biology and medicine: a review. Cancer Biother. 1995;10(4):257-264. View abstract.

Nair, S. C., Panikkar, K. R., and Parthod, R. K. Protective effects of crocetin on the bladder toxicity induced by cyclophosphamide. Cancer Biother. 1993;8(4):339-343. View abstract.

Nair, S. C., Salomi, M. J., Panikkar, B., and Panikkar, K. R. Modulatory effects of Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in mice. J Ethnopharmacol. 1991;31(1):75-83. View abstract.

Nemati, H., Boskabady, M. H., and Ahmadzadef, Vostakolaei H. Stimulatory effect of Crocus sativus (saffron) on beta2-adrenoceptors of guinea pig tracheal chains. Phytomedicine. 2008;15(12):1038-1045. View abstract.

Notas, G., Miliaraki, N., Kampa, M., Dimoulios, F., Matrella, E., Hatzidakis, A., Castanas, E., and Kouroumalis, E. Patients with primary biliary cirrhosis have increased serum total antioxidant capacity measured with the crocin bleaching assay. World J Gastroenterol. 7-21-2005;11(27):4194-4198. View abstract.

Ochiai, T., Ohno, S., Soeda, S., Tanaka, H., Shoyama, Y., and Shimeno, H. Crocin prevents the death of rat pheochromyctoma (PC-12) cells by its antioxidant effects stronger than those of alpha-tocopherol. Neurosci.Lett. 5-13-2004;362(1):61-64. View abstract.

Ochiai, T., Shimeno, H., Mishima, K., Iwasaki, K., Fujiwara, M., Tanaka, H., Shoyama, Y., Toda, A., Eyanagi, R., and Soeda, S. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochim.Biophys.Acta 2007;1770(4):578-584. View abstract.

Ochiai, T., Soeda, S., Ohno, S., Tanaka, H., Shoyama, Y., and Shimeno, H. Crocin prevents the death of PC-12 cells through sphingomyelinase-ceramide signaling by increasing glutathione synthesis. Neurochem.Int. 2004;44(5):321-330. View abstract.

Ordoudi, S. A. and Tsimidou, M. Z. Crocin bleaching assay (CBA) in structure-radical scavenging activity studies of selected phenolic compounds. J Agric.Food Chem. 12-13-2006;54(25):9347-9356. View abstract.

Ordoudi, S. A. and Tsimidou, M. Z. Crocin bleaching assay step by step: observations and suggestions for an alternative validated protocol. J Agric.Food Chem. 3-8-2006;54(5):1663-1671. View abstract.

Ordoudi, S. A., Befani, C. D., Nenadis, N., Koliakos, G. G., and Tsimidou, M. Z. Further examination of antiradical properties of Crocus sativus stigmas extract rich in crocins. J Agric.Food Chem. 4-22-2009;57(8):3080-3086. View abstract.

Osswald, W. F., Schutz, W., and Elstner, E. F. Indole-3-Acetic Acid Oxidation and Crocin Bleaching by Horseradish Peroxidase. Plant Physiol 1988;86(4):1310-1314. View abstract.

Papandreou, M. A., Kanakis, C. D., Polissiou, M. G., Efthimiopoulos, S., Cordopatis, P., Margarity, M., and Lamari, F. N. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric.Food Chem. 11-15-2006;54(23):8762-8768. View abstract.

Pathan, S. A., Alam, S., Jain, G. K., Zaidi, S. M., Akhter, S., Vohora, D., Khar, R. K., and Ahmad, F. J. Quantitative analysis of safranal in saffron extract and nanoparticle formulation by a validated high-performance thin-layer chromatographic method. Phytochem.Anal. 2010;21(3):219-223. View abstract.

Pitsikas, N. and Sakellaridis, N. Crocus sativus L. extracts antagonize memory impairments in different behavioural tasks in the rat. Behav.Brain Res 10-2-2006;173(1):112-115. View abstract.

Pitsikas, N., Boultadakis, A., Georgiadou, G., Tarantilis, P. A., and Sakellaridis, N. Effects of the active constituents of Crocus sativus L., crocins, in an animal model of anxiety. Phytomedicine. 2008;15(12):1135-1139. View abstract.

Pitsikas, N., Zisopoulou, S., Tarantilis, P. A., Kanakis, C. D., Polissiou, M. G., and Sakellaridis, N. Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats' memory. Behav.Brain Res 11-2-2007;183(2):141-146. View abstract.

Premkumar, K., Abraham, S. K., Santhiya, S. T., and Ramesh, A. Inhibitory effects of aqueous crude extract of Saffron (Crocus sativus L.) on chemical-induced genotoxicity in mice. Asia Pac.J Clin Nutr. 2003;12(4):474-476. View abstract.

Premkumar, K., Abraham, S. K., Santhiya, S. T., and Ramesh, A. Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother.Res 2003;17(6):614-617. View abstract.

Premkumar, K., Kavitha, S., Santhiya, S. T., Ramesh, A. R., and Suwanteerangkul, J. Interactive effects of saffron with garlic and curcumin against cyclophosphamide induced genotoxicity in mice. Asia Pac.J Clin Nutr. 2004;13(3):292-294. View abstract.

Roy, J. W., Graham, M. C., Griffin, A. M., and Gainer, J. L. A novel fluid resuscitation therapy for hemorrhagic shock. Shock 1998;10(3):213-217. View abstract.

Rubio, A., Rambla, J. L., Santaella, M., Gomez, M. D., Orzaez, D., Granell, A., and Gomez-Gomez, L. Cytosolic and plastoglobule-targeted carotenoid dioxygenases from Crocus sativus are both involved in beta-ionone release. J Biol.Chem. 9-5-2008;283(36):24816-24825. View abstract.

Rubio-Moraga, A., Castillo-Lopez, R., Gomez-Gomez, L., and Ahrazem, O. Saffron is a monomorphic species as revealed by RAPD, ISSR and microsatellite analyses. BMC.Res Notes 2009;2:189. View abstract.

Sadeghnia, H. R., Cortez, M. A., Liu, D., Hosseinzadeh, H., and Snead, O. C., III. Antiabsence effects of safranal in acute experimental seizure models: EEG and autoradiography. J Pharm Pharm Sci. 2008;11(3):1-14. View abstract.

Sako, F., Kobayashi, N., Taniguchi, N., and Takakuwa, E. A study on the toxicity of natural food dyes--toxicity and enzyme inhibition in Paramecium caudatum. J Toxicol Sci. 1978;3(2):127-136. View abstract.

Saleem, S., Ahmad, M., Ahmad, A. S., Yousuf, S., Ansari, M. A., Khan, M. B., Ishrat, T., and Islam, F. Effect of Saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats. J Med.Food 2006;9(2):246-253. View abstract.

Salomi, M. J., Nair, S. C., and Panikkar, K. R. Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr Cancer 1991;16(1):67-72. View abstract.

Sanchez, A. M., Carmona, M., Ordoudi, S. A., Tsimidou, M. Z., and Alonso, G. L. Kinetics of individual crocetin ester degradation in aqueous extracts of saffron (Crocus sativus L.) upon thermal treatment in the dark. J Agric.Food Chem. 3-12-2008;56(5):1627-1637. View abstract.

Sanchez, A. M., Carmona, M., Prodanov, M., and Alonso, G. L. Effect of centrifugal ultrafiltration on the composition of aqueous extracts of saffron spice (Crocus sativus L.). J Agric.Food Chem. 8-27-2008;56(16):7293-7301. View abstract.

Sanchez, A. M., Carmona, M., Zalacain, A., Carot, J. M., Jabaloyes, J. M., and Alonso, G. L. Rapid determination of crocetin esters and picrocrocin from saffron spice (Crocus sativus L.) using UV-visible spectrophotometry for quality control. J Agric.Food Chem. 5-14-2008;56(9):3167-3175. View abstract.

Sarris, J. Herbal medicines in the treatment of psychiatric disorders: a systematic review. Phytother.Res 2007;21(8):703-716. View abstract.

Schmidt, M., Betti, G., and Hensel, A. Saffron in phytotherapy: pharmacology and clinical uses. Wien.Med.Wochenschr. 2007;157(13-14):315-319. View abstract.

Sengul, M., Yildiz, H., Gungor, N., Cetin, B., Eser, Z., and Ercisli, S. Total phenolic content, antioxidant and antimicrobial activities of some medicinal plants. Pak.J Pharm Sci. 2009;22(1):102-106. View abstract.

Seyde, W. C., McKernan, D. J., Laudeman, T., Gainer, J. L., and Longnecker, D. E. Carotenoid compound crocetin improves cerebral oxygenation in hemorrhaged rats. J Cereb.Blood Flow Metab 1986;6(6):703-707. View abstract.

Shahrokhabadi KN, Afshari JT, Rakhshandeh H, and Barouk A. Study of cytotoxicity effect of total saffron extract on hepatocarcinoma cell line (HepG2). Medical Sciences Journal of Islamic Azad University Tehran Medical Branch 2009;19(3):4.

Sheehan, J., Ionescu, A., Pouratian, N., Hamilton, D. K., Schlesinger, D., Oskouian, R. J., Jr., and Sansur, C. Use of trans sodium crocetinate for sensitizing glioblastoma multiforme to radiation: laboratory investigation. J Neurosurg. 2008;108(5):972-978. View abstract.

Shen, X. C. and Qian, Z. Y. Effect of crocetin on cardiac hypertrophy induced by overloading pressure in rats. Yao Xue.Xue.Bao. 2004;39(3):172-175. View abstract.

Shen, X. C. and Qian, Z. Y. Effects of crocetin on antioxidant enzymatic activities in cardiac hypertrophy induced by norepinephrine in rats. Pharmazie 2006;61(4):348-352. View abstract.

Shen, X. C., Qian, Z. Y., Wang, Y. J., and Duan, J. A. Crocetin attenuates norepinephrine-induced cytotoxicity in primary cultured rat cardiac myocytes by antioxidant in vitro. J Asian Nat.Prod.Res 2009;11(5):417-425. View abstract.

Shen, X. C., Y-Lu, and Qian, Z. Y. Effects of crocetin on the matrix metalloproteinases in cardiac hypertrophy induced by norepinephrine in rats. J Asian Nat.Prod.Res 2006;8(3):201-208. View abstract.

Sheng, L., Qian, Z., Shi, Y., Yang, L., Xi, L., Zhao, B., Xu, X., and Ji, H. Crocetin improves the insulin resistance induced by high-fat diet in rats. Br.J Pharmacol 2008;154(5):1016-1024. View abstract.

Singer, M., Stidwill, R. P., Nathan, A., and Gainer, J. L. Intravenous crocetinate prolongs survival in a rat model of lethal hypoxemia. Crit Care Med. 2000;28(6):1968-1972. View abstract.

Singh, U. P., Singh, D. P., Maurya, S., Maheshwari, R., Singh, M., Dubey, R. S., and Singh, R. B. Investigation on the phenolics of some spices having pharmacotherapeuthic properties. J Herb.Pharmacother. 2004;4(4):27-42. View abstract.

Soeda, S., Ochiai, T., Paopong, L., Tanaka, H., Shoyama, Y., and Shimeno, H. Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells. Life Sci. 11-2-2001;69(24):2887-2898. View abstract.

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