Drug Res (Stuttg) 2015; 65(06): 287-295
DOI: 10.1055/s-0034-1375681
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Clinical Applications of Saffron (Crocus sativus) and its Constituents: A Review

M. Moshiri
1   Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR. Iran
,
M. Vahabzadeh
1   Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR. Iran
2   Medical Toxicology Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
,
H. Hosseinzadeh
3   Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
› Author Affiliations
Further Information

Publication History

received 11 November 2013

accepted 21 February 2014

Publication Date:
21 May 2014 (online)

Abstract

Commonly known as saffron, Crocus sativus L and its active components have shown several useful pharmacological effects such as anticonvulsant, antidepressant, anti-inflammatory, antitumor, radical scavenger effects, learning and memory improving effects, etc. There has been an increasing body of data on saffron use in medical databases within the last 20 years. In the current review, the strengths and weaknesses of some of the clinical trials about different pharmacological effects of saffron will be discussed

C. sativus extract has been studied in 8 anti-depressant clinical trials in comparison to placebo or some antidepressant drugs, in which saffron showed effectiveness as an antidepressant drug. Clinical trials on anti-Alzheimer effect of saffron demonstrated that it was more effective than the placebo, and as effective as donepezil. 2 clinical trials on antipruritic and complexion promoter in skin care effects of saffron both confirmed that saffron was more efficient than the placebo. In another clinical trial, it was proved that in addition to the weight loss treatment, saffron could reduce snacking frequency. Clinical trials conducted on women with premenstrual syndrome showed that saffron could reduce suffering symptoms more than the placebo and similar to standard treatments.

Furthermore, additional clinical trials on effects of saffron on erection dysfunction, allergies, cardiovascular and immune system as well as its safety, toxicity and human pharmacokinetics are reviewed herein.

 
  • References

  • 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 HR. 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 KN, Park YM, Jung HJ 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 HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol 2002; 2: 7
  • 9 Nair SC, Pannikar B, Panikkar KR. 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 HR, Ghaeni FA 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 SK, Santhiya ST 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 SA, 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 HR, 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 SS 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 CK, Bhat GV. Crocin: An Overview. Indo Glo J Pharmaceu Sci 2011; 1: 281-286
  • 25 Liu TZ, Qian ZY. 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 MV et al. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration. Phytomedicine 2011; 18: 575-578
  • 28 Modaghegh MH, Shahabian M, Esmaeili HA 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 AH, Ayati Z, Parizadeh MR 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 SY, Qian ZY, Tang FT et al. Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci 2005; 77: 907-921
  • 35 Xu GL, Yu SQ, Gong ZN 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 MS, Harirchian MH 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 MH 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 AA 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 AA, Noorbala AA 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 PA, O’Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol 2004; 57: 121-126
  • 42 Chang PY, Wang CK, Liang JD 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 MR, Khooei AR 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 SN, Arora S, Sharma AK 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 MH, Shafei MN, 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 JL, Chisolm 3rd GM. 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 SK, 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 MJ, Perry E. The role of phytochemicals in the treatment and prevention of dementia. Drugs Aging 2011; 28: 439-468
  • 55 Ebrahim-Habibi MB, 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 HR. 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 MA, Kanakis CD, Polissiou MG 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 AA, 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 GR, 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 NB. 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 AA 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 Burke MJ, Preskorn SH. Standard antidepressant pharmacotherapy for the acute treatment of mood disorders. In: Bloom EF, Kupfer DJ. ed. Psychopharmacology – 4th 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 Masinaei Nezhad N, Abdullahi Mohammad AQ, Hashemi Bonjar ZS et al. Effect of Crocus sativus L. (Saffron) on depression among students of zabol faculty of medical sciences 2005. J Neurol Sci 2005; 238 (Supplement 1) (Abstracts of the XVIIIth World 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 MC, Vina J, Ji LL. Interplay of oxidants and antioxidants during exercise: implications for muscle health. Phys Sportsmed 2009; 37: 116-123
  • 73 Reid MB. Free radicals and muscle fatigue: Of ROS, canaries, and the IOC. Free Radic Biol Med 2008; 44: 169-179
  • 74 Hosseinzadeh H, Modaghegh MH, 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 MR, 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 MR, 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 RB. 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 AS. 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 DJ, Hetherington MM. 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 MR, Hosseinzadeh H. Does Saffron have antisolar and moisturizing effects?. IJPR 2010; 9: 133-140
  • 92 Vyas LK, Tapar KK, Nema RK. Study of Crocus sativus as complexion promoter in skin care. IJPCR 2010; 2: 76-79
  • 93 Hosseinzadeh H, Abootorabi A, Sadeghnia HR. 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 RN, 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