Clinical applications of saffron (Crocus sativus) and its constituents: A review

Drug Research

Volumn 65, Issue 6, 2015, Pages 287-295

  Moshiri, M ^a   Vahabzadeh, M ^a,b   Hosseinzadeh, H ^a  

^a MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

clinical; crocin; Crocus sativus; saffron; safranal

Indexed keywords

CROCUS SATIVUS EXTRACT; DONEPEZIL; ANTIDEPRESSANT AGENT; ANTIPRURITIC AGENT; PLANT EXTRACT;

ALLERGY; ALZHEIMER DISEASE; ANTIDEPRESSANT ACTIVITY; ARTICLE; CARDIOVASCULAR SYSTEM; CLINICAL TRIAL (TOPIC); COMPARATIVE STUDY; CONSTIPATION; CONTROLLED CLINICAL TRIAL (TOPIC); CROCUS SATIVUS; DECREASED APPETITE; DEPRESSION; DIARRHEA; DIZZINESS; DROWSINESS; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DYSMENORRHEA; ERECTILE DYSFUNCTION; FATIGUE; HEADACHE; HUMAN; HYPOMANIA; IMMUNE SYSTEM; INCREASED APPETITE; INFERTILITY; INSOMNIA; MOOD DISORDER; NAUSEA; NONHUMAN; PARESTHESIA; PREMENOPAUSE; PREMENSTRUAL SYNDROME; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESTLESSNESS; SEXUAL DYSFUNCTION; SIDE EFFECT; SKIN CARE; SKIN TINGLING; STOMACH PAIN; TREMOR; URINE RETENTION; VOMITING; WEIGHT REDUCTION; XEROSTOMIA; ANIMAL; CHEMISTRY; CROCUS; DRUG EFFECTS; FEMALE;

ALZHEIMER DISEASE; ANIMALS; ANTIDEPRESSIVE AGENTS; ANTIPRURITICS; CLINICAL TRIALS AS TOPIC; CROCUS; FEMALE; HUMANS; PLANT EXTRACTS; PREMENSTRUAL SYNDROME; WEIGHT LOSS;

EID: 84930414392     PISSN: 21949379     EISSN: 21949387     Source Type: Journal    
DOI: 10.1055/s-0034-1375681     Document Type: Article

References (94)

1. Kianbakht S. A systematic review on pharmacology of saffron and its active constituents. J Med Plants: 2009; 28 1 23 (in persion)
2. Koocheki A., Ganjeali A., Abbassil F. The effect of duration and condition of incubation, weight of mother corms and photoperiod on corm and shoot characteristics of saffron plant (Crocus sativus L.). J Iran Field Crop Res: 2006; 4 20 25 (in persion)
3. Hosseinzadeh H., Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia: 2005; 76 722 724
4. Hosseinzadeh H., Sadeghnia H. R. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: involvement of GABAergic and opioids systems. Phytomedicine: 2007; 14 256 262
5. Wang Y., Han T., Zhu Y. et al. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med. 2010; 64 24 30
6. Hosseinzadeh H., Karimi G., Niapoor M. Antidepressant effects of Crocus sativus stigma extracts and its constituents, crocin and safranal, in mice. J Med Plants: 2004; 3 48 58
7. Nam K. N., Park Y. M., Jung H. J. et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol: 2010; 648 110 116
8. Hosseinzadeh H., Younesi H. M. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol: 2002; 2 7
9. Nair S. C., Pannikar B., Panikkar K. R. Antitumour activity of saffron (Crocus sativus). Cancer Lett: 1991; 57 109 114
10. Zhang Y., Shoyama Y., Sugiura M. et al. Effects of Crocus sativus L. on the ethanol-induced impairment of passive avoidance performances in mice. Biol Pharm Bull: 1994; 17 217 221
11. Abe K., Saito H. Effects of saffron extract and its constituent crocin on learning behaviour and long-term potentiation. Phytother Res: 2000; 14 149 152
12. Hosseinzadeh H., Sadeghnia H. R., Ghaeni F. A. et al. Effects of saffron (Crocus sativus l.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother Res: 2012; 26 381 386
13. Hosseinzadeh H., Ziaei T. Effects of Crocus sativus stigma extract and its constituents, crosin and safranal, on intact memory and scopolamine -indused learning deficits in rats performing the Morris water maze task. J Med Plants: 2006; 5 40 50
14. Abdullaev Jafarova F., Caballero-Ortega H., Riveron-Negrete L. et al. In vitro evaluation of the chemopreventive potential of saffron. Rev Invest Clin: 2002; 54 430 436
15. Premkumar K., Abraham S. K., Santhiya S. T. et al. Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother Res: 2003; 17 614 617
16. Mohajeri S. A., Hosseinzadeh H., Abbasi-Ghaeni F. Saffron (Crocus sativus L.) and crocin have memory enhancing effect after chronic cerebral hypoperfusion in rats. J Clinbiochem: 2011; 8 274
17. Hosseinzadeh H., Sadeghnia H. R., Ziaee T. et al. 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; 8 387 393
18. Mansoori P., Akhondzadeh S., Raisi F. et al. A Randomized, Double-blind, Placebo - controlled Study of Safety of the Adjunctive Saffron on Sexual Dysfunction Induced by a Selective. J Med Plants: 2011; 10 121 130
19. Ramadan A., Soliman G., Mahmoud S. S. et al. Evaluation of the safety and antioxidant activitie s of Crocus sativus and Propolis ethanolic extracts. J Saudi Chem Soci: 2012; 16 13 21
20. Mansoori P., Akhondzadeh S., Raisi F. et al. A randomized, double-blind, placebo-controled, study of safety the adjunctive saffron on sexual dysfunction induced by selective sertonin reuptake inhibitor. J Med Plants: 2011; 10 121 130
21. Mohajeri D., Mousavi G., Mesgari M. et al. Subacute toxicity of Crocus sativus l. (saffron) stigma ethanolic extract in rats. Am J Pharma Toxi: 2007; 2 189 193
22. Asai A., Nakano T., Takahashi M. et al. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J Agric Food Chem: 2005; 53 7302 7306
23. Xi L., Qian Z., Du P. et al. Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats. Phytomedicine: 2007; 14 633 636
24. Singla C. K., Bhat G. V. Crocin: An Overview. Indo Glo J Pharmaceu Sci: 2011; 1 281 286
25. Liu T. Z., Qian Z. Y. Pharmacokinetics of crocetin in rats. Yao Xue Xue Bao: 2002; 37 367 369
26. Tang L., Yan F., Xu Y. et al. Determination of crocin-1 in rabbit plasma and the pharmacokinetics by RP-HPLC. Yao Xue Xue Bao: 2004; 39 854 856
27. Umigai N., Murakami K., Ulit M. V. et al. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration. Phytomedicine: 2011; 18 575 578
28. Modaghegh M. H., Shahabian M., Esmaeili H. A. et al. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers. Phytomedicine: 2008; 15 1032 1037
29. Drugs.com:. Saffron http://www.drugs.com/npp/saffron.html: 2012
30. Rx-list (The internt drug index). saffron, http://www.rxlist.com/saffron-page2/supplements.htm (Accessed 14/5/2012) http://www.rxlist.com/saffron-page2/supplements.htm
31. Schmidt M., Betti G., Hensel A. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr: 2007; 157 315 319
32. Mohamadpour A. H., Ayati Z., Parizadeh M. R. et al. Safety Evaluation of Crocin (a constituent of saffron) Tablets in Healthy Volunteers. Iran J Basic Med Sci: 2013; 15 24 31
33. Okano K., Nishio T., Fukaya C. et al. Isolation and identification of a platelet aggregation inhibitor from saffron (Crocus sativus Linne, Iridaceae). Wakan Iyaku Gakka ish: 1992; 9 175 181
34. He S. Y., Qian Z. Y., Tang F. T. et al. Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci: 2005; 77 907 921
35. Xu G. L., Yu S. Q., Gong Z. N. et al. Study of the effect of crocin on rat experimental hyperlipemia and the underlying mechanisms. Zhongguo Zhong Yao Za Zhi: 2005; 30 369 372
36. Akhondzadeh S., Sabet M. S., Harirchian M. H. et al. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial. J Clin Pharm Ther: 2010; 35 581 588
37. Akhondzadeh S., Shafiee Sabet M., Harirchian M. H. et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacol (Berl): 2010; 207 637 643
38. Akhondzadeh S., Tahmacebi-Pour N., Noorbala A. A. et al. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res: 2005; 19 148 151
39. Moshiri E., Basti A. A., Noorbala A. A. et al. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine: 2006; 13 607 611
40. Gout B., Bourges C., Paineau-Dubreuil S. Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women. Nutr Res: 2010; 30 305 313
41. Routledge P. A., O'Mahony M. S., Woodhouse K. W. Adverse drug reactions in elderly patients. Br J Clin Pharmacol: 2004; 57 121 126
42. Chang P. Y., Wang C. K., Liang J. D. et al. Studies on the pharmacological action of zang hong hua (Crocus sativus l.). i. effects on uterus and estrus cycle. Yao Xue Xue Bao: 1964; 11 94 100
43. Mehdizadeh R., Parizadeh M. R., Khooei A. R. et al. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced myocardial infarction in Wistar rats. Iran J Basic Med Sci: 2013; 16 56 63
44. Goyal S. N., Arora S., Sharma A. K. et al. Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats. Phytomedicine: 2011; 17 227 232
45. Imenshahidi M., Hosseinzadeh H., Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res: 2010; 24 990 994
46. Boskabady M. H., Shafei M. N., Shakiba A. et al. Effect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig isolated heart. Phytother Res: 2008; 22 330 334
47. Gainer J. L., Chisolm G. M. 3rd. Oxygen diffusion and atherosclerosis. Atheroscl: 1974; 19 135 138
48. Zheng S., Qian Z., Tang F. et al. Suppression of vascular cell adhesion molecule-1 expression by crocetin contributes to attenuation of atherosclerosis in hypercholesterolemic rabbits. Bioch Pharmacol: 2005; 70 1192 1199
49. Grisolia S. Letter: Hypoxia, saffron, and cardiovascular disease. Lancet: 1974; 2 41 42
50. Kamalipour M., Akhondzadeh S. Cardiovascular Effects of Saffron: An Evidence-Based Review. J Teh Univ Heart Cent: 2011; 6 59 61
51. Verma S. K., Bordia A. Antioxidant property of Saffron in man. Indian J Med Sci: 1998; 52 205
52. Mancuso C., Siciliano R., Barone E. et al. Pharmacologists and Alzheimer disease therapy: to boldly go where no scientist has gone before. Exp Opin Investig Drugs: 2011; 20 1243 1261
53. Reitz C., Brayne C., Mayeux R. Epidemiology of Alzheimer disease. Nat Rev Neurol: 2011; 7 137 152
54. Howes M. J., Perry E. The role of phytochemicals in the treatment and prevention of dementia. Drugs Aging: 2011; 28 439 468
55. Ebrahim-Habibi M. B., Amininasab M., Ebrahim-Habibi A. et al. Fibrillation of alpha-lactalbumin: effect of crocin and safranal, two natural small molecules from Crocus sativus. Biopolym: 2010; 93 854 865
56. Hosseinzadeh H., Sadeghnia H. R. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci: 2005; 8 394 399
57. Papandreou M. A., Kanakis C. D., Polissiou M. G. et al. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem: 2006; 54 8762 8768
58. Shams J., Hedayati M., Asefi F. et al. Water extract of saffron (Crocus sativus) increases brain dopamine and glutamate concentration in the rat. Eur Neuropsychopharmacol: 2010; 20 S353
59. Abe K., Sugiura M., Yamaguchi S. et al. Saffron extract prevents acetaldehyde-induced inhibition of long-term potentiation in the rat dentate gyrus in vivo. Brain Res: 1999; 851 287 289
60. Akhondzadeh S., Fallah-Pour H., Afkham K. et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med: 2004; 4 12
61. Hosseinzadeh H., Karimi G., Niapoor M. Antidepressant effect of Crocus sativus L. extracts and their constituents, Crocin and safranal, in mice. In: Fernández J-A, Abdullaev F. eds. first International Symposium on Saffron Biology and Biotechnology 2004. Albacete, Spain: 2004
62. Noorbala A. A., Akhondzadeh S., Tahmacebi-Pour N. et al. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol: 2005; 97 281 284
63. Hosseinzadeh H., Motamedshariaty V., Hadizadeh F. Antidepressant effect of kempferol, a constituent of saffron (Crocus sativus) petal, in mice and rat. Pharmacologyonline: 2007; 2 367 370
64. Karimi G. R., Hosseinzadeh H., Khaleghpanah P. Study of antidepressant effect of aqueous and ethanolic of Crocus sativus in mice. IJBMS: 2001; 4 11 15
65. Hosseinzadeh H., Noraei N. B. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res: 2009; 23 768 774
66. Akhondzadeh Basti A., Moshiri E., Noorbala A. A. et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry: 2007; 31 439 442
67. th Generation of Progress. New York Raven Press: 1995
68. Sarris J., Panossian A., Schweitzer I. et al. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol: 2011; 21 841 860
69. Agha-Hosseini M., Kashani L., Aleyaseen A. et al. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. Bjog: 2008; 115 515 519
70. thWorld Congress of Neurology) S1 S570
71. Shemshian M., Sadeghi A., Kermani T. et al. Saffron (Crocus sativus) in the treatment of anxiety and depression: a double-blind, randomized and placebo-controlled trial. Clin Biochem: 2011; 44 S118
72. Gomez-Cabrera M. C., Vina J., Ji L. L. Interplay of oxidants and antioxidants during exercise: implications for muscle health. Phys Sportsmed: 2009; 37 116 123
73. Reid M. B. Free radicals and muscle fatigue: Of ROS, canaries, and the IOC. Free Radic Biol Med: 2008; 44 169 179
74. Hosseinzadeh H., Modaghegh M. H., 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; 6 343 350
75. Mizuma H., Tanaka M., Nozaki S. et al. Daily oral administration of crocetin attenuates physical fatigue in human subjects. Nutr Res: 2009; 29 145 150
76. Hosseinzadeh H., Ziaee T., 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; 15 491 495
77. Shamsa A., Hosseinzadeh H., Molaei M. et al. Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: a pilot study. Phytomedicine: 2009; 16 690 693
78. Safarinejad M. R., Shafiei N., Safarinejad S. An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for treating erectile dysfunction in men naive to treatment. Int J Impot Res: 2010; 22 240 250
79. Safarinejad M. R., Shafiei N., Safarinejad S. A prospective double-blind randomized placebo-controlled study of the effect of saffron (Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia. Phytother Res: 2011; 25 508 516
80. Sultana A., ur Rahman K., Nagaraj R. B. Conception in unilateral right tubal blockage with herbomineral formulations: a case report. J Altern Complement Med: 2011; 17 557 561
81. Dante G., Facchinetti F. Herbal treatments for alleviating premenstrual symptoms: a systematic review. J Psychosom Obstet Gynaecol: 2011; 32 42 51
82. Coco A. S. Primary dysmenorrhea. Am Fam Physician: 1999; 60 489 496
83. Nahid K., Fariborz M., Ataolah G. et al. The effect of an Iranian herbal drug on primary dysmenorrhea: a clinical controlled trial. J Midwifery Womens Health: 2009; 54 401 404
84. Fukui H., Toyoshima K., Komaki R. Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus). Phytomedicine: 2011; 18 726 730
85. Wallis D. J., Hetherington M. M. Emotions and eating. Self-reported and experimentally induced changes in food intake under stress. Appetite: 2009; 52 355 362
86. Feo F., Martinez J., Martinez A. et al. Occupational allergy in saffron workers. Allergy: 1997; 52 633 641
87. Varasteh A., Rahim Zadeh M., Farid Hosseini R. et al. Determination of saffron (Crocus sativus) allergenicity. IJBMS: 2000; 3 33 37
88. Kianbakht S., Ghazavi A. Immunomodulatory effects of saffron: a randomized double-blind placebo-controlled clinical trial. Phytother Res: 2011; 25 1801 1805
89. Abdullaev F. Biological properties and medicinal use of saffron (Crocus sativus L.). Acta Hort (ISHS): 2007; 739 339 345
90. Konoshima T., Takasaki M., Tokuda H. et al. Crocin and crocetin derivatives inhibit skin tumour promotion in mice. Phytother Res: 1998; 12 400 404
91. Golmohammadzadeh S., Jaafari M. R., Hosseinzadeh H. Does Saffron have antisolar and moisturizing effects? IJPR: 2010; 9 133 140
92. Vyas L. K., Tapar K. K., Nema R. K. Study of Crocus sativus as complexion promoter in skin care. IJPCR: 2010; 2 76 79
93. Hosseinzadeh H., Abootorabi A., 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; 27 657 664
94. Chatterjee S., Datta R. N., Bhattacharyya D. et al. Emollient and antipruritic effect of Itch cream in dermatological disorders: A randomized controlled trial. Indian J Pharmacol: 2005; 37 253 254