Saffron (Crocus sativus) for depression: A systematic review of clinical studies and examination of underlying antidepressant mechanisms of action

Human Psychopharmacology

Volumn 29, Issue 6, 2014, Pages 517-527

  Lopresti, Adrian L ^a   Drummond, Peter D ^a  

^a MURDOCH UNIVERSITY   (Australia)

Author keywords

antidepressant; Crocus sativus; depression; review; saffron

Indexed keywords

ANTIDEPRESSANT AGENT; PLANT MEDICINAL PRODUCT;

ANIMAL; CROCUS; DEPRESSIVE DISORDER; HUMAN; PATHOPHYSIOLOGY; PHYTOTHERAPY; RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANIMALS; ANTIDEPRESSIVE AGENTS; CROCUS; DEPRESSIVE DISORDER; HUMANS; PHYTOTHERAPY; PLANT PREPARATIONS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84912139884     PISSN: 08856222     EISSN: 10991077     Source Type: Journal    
DOI: 10.1002/hup.2434     Document Type: Review

References (86)

1. Agha-Hosseini M, Kashani L, Aleyaseen A, et al,. 2008. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. Bjog 115: 515-519.
2. Ahmad AS, Ansari MA, Ahmad M, et al,. 2005. Neuroprotection by crocetin in a hemi-Parkinsonian rat model. Pharmacol Biochem Behav 81: 805-813.
3. Akhondzadeh Basti A, Moshiri E, Noorbala AA, Jamshidi AH, Abbasi SH, Akhondzadeh S,. 2007. 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 31: 439-442.
4. Akhondzadeh Basti A, Ghoreishi SA, Noorbala AA, Akhondzadeh SH, Rezazadeh SH,. 2008. Petal and stigma of Crocus sativus L. in the treatment of depression: a pilot double-blind randomized trial. J Med Plants Res 7: 29-36.
5. Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F,. 2004. 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 4: 12.
6. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al,. 2005. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res 19: 148-151.
7. Akhondzadeh S, Sabet MS, Harirchian MH, et al,. 2010a. 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 35: 581-588.
8. Akhondzadeh S, Shafiee Sabet M, Harirchian MH, et al,. 2010b. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology (Berl) 207: 637-643.
9. Alavizadeh SH, Hosseinzadeh H,. 2014. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem Toxicol 64: 65-80.
10. Anderson G, Berk M, Dean O, Moylan S, Maes M,. 2014. Role of immune-inflammatory and oxidative and nitrosative stress pathways in the etiology of depression: therapeutic implications. CNS Drugs 28: 1-10.
11. Asdaq SM, Inamdar MN,. 2010. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Appl Biochem Biotechnol 162: 358-372.
12. Ayatollahi H, Javan AO, Khajedaluee M, Shahroodian M, Hosseinzadeh H,. 2014. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytother Res 28: 593-543.
13. Bani S, Pandey A, Agnihotri VK, Pathania V, Singh B,. Selective Th2 upregulation by Crocus sativus: a neutraceutical spice. Evid Based Complement Alternat Med 2011. Article ID 639862. DOI: 10.1155/2011/639862
14. Carr GV, Lucki I,. 2011. The role of serotonin receptor subtypes in treating depression: a review of animal studies. Psychopharmacology (Berl) 213: 265-287.
15. Cowen PJ,. 1990. A role for 5-HT in the action of antidepressant drugs. Pharmacol Ther 46: 43-51.
16. Dowlati Y, Herrmann N, Swardfager W, et al,. 2010. A meta-analysis of cytokines in major depression. Biol Psychiatry 67: 446-457.
17. Duman RS,. 2009. Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci 11: 239-255.
18. Duman RS, Monteggia LM,. 2006. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59: 1116-1127.
19. El-Beshbishy HA, Hassan MH, Aly HA, Doghish AS, Alghaithy AA, 2012. Crocin "saffron" protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. Ecotoxicol Environ Saf 83: 47-54.
20. Falsini B, Piccardi M, Minnella A, et al,. 2010. Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci 51: 6118-6124.
21. Farahmand SK, Samini F, Samini M, Samarghandian S,. 2013. Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver. Biogerontology 14: 63-71.
22. Fukui H, Toyoshima K, Komaki R,. 2011. Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus). Phytomedicine 18: 726-730.
23. Georgiadou G, Tarantilis PA, Pitsikas N,. 2012. Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder. Neurosci Lett 528: 27-30.
24. Ghadrdoost B, Vafaei AA, Rashidy-Pour A, et al,. 2011. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol 667: 222-229.
25. Ghasemi T, Abnous K, Vahdati F, Mehri S, Razavi BM, Hosseinzadeh H,. Antidepressant effect of Crocus sativus aqueous extract and its effect on CREB, BDNF, and VGF transcript and protein levels in rat hippocampus. Drug Res (Stuttg) 2014. Epub ahead of print, 2 April 2014. DOI: 10.1055/s-0034-1371876
26. Gohari AR, Saeidnia S, Mahmoodabadi MK,. 2013. An overview on saffron, phytochemicals, and medicinal properties. Pharmacogn Rev 7: 61-66.
27. Halataei BA, Khosravi M, Arbabian S, et al,. 2011. Saffron (Crocus sativus) aqueous extract and its constituent crocin reduces stress-induced anorexia in mice. Phytother Res 25: 1833-1838.
28. Hannestad J, DellaGioia N, Bloch M,. 2011. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacol 36: 2452-2459.
29. Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H,. 2010. Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: protective effects of crocin and safranal. Food Chem Toxicol 48: 2803-2808.
30. Hausenblas HA, Saha D, Dubyak PJ, Anton SD,. 2013. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med 11: 377-383.
31. Hemshekhar M, Sebastin Santhosh M, Sunitha K, et al,. 2012. A dietary colorant crocin mitigates arthritis and associated secondary complications by modulating cartilage deteriorating enzymes, inflammatory mediators and antioxidant status. Biochimie 94: 2723-2733.
32. Hiles SA, Baker AL, de Malmanche T, Attia J,. 2012. A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: exploring the causes of heterogeneity. Brain Behav Immun 26: 1180-1188.
33. Hood SD, Bell CJ, Nutt DJ,. 2005. Acute tryptophan depletion. Part I: rationale and methodology. Aust N Z J Psychiatry 39: 558-564.
34. Hooshmandi Z, Rohani AH, Eidi A, Fatahi Z, Golmanesh L, Sahraei H,. 2011. Reduction of metabolic and behavioral signs of acute stress in male Wistar rats by saffron water extract and its constituent safranal. Pharm Biol 49: 947-954.
35. Hosseinzadeh H, Nassiri-Asl M,. 2013. Avicenna's (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res 27: 475-483.
36. Hosseinzadeh H, Motamedshariaty VS, Hadizadeh F,. 2007. Antidepressant effect of kaempferol, a constituent of saffron (Crocus sativus) petal, in mice and rats. Pharmacologyonline 2: 367-370.
37. Howren MB, Lamkin DM, Suls J,. 2009. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71: 171-186.
38. Jadad AR, Moore RA, Carroll D, et al,. 1996. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17: 1-12.
39. Jiang C, Salton SR,. 2013. The role of neurotrophins in major depressive disorder. Transl Neurosci 4: 46-58.
40. Kashani L, Raisi F, Saroukhani S, et al,. 2013. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study. Hum Psychopharmacol 28: 54-60.
41. Kawabata K, Tung NH, Shoyama Y, Sugie, S, Mori T, Tanaka T,. 2012. Dietary crocin inhibits colitis and colitis-associated colorectal carcinogenesis in male ICR mice. Evid Based Complement Alternat Med 2012: 820415.
42. Kempton MJ, Salvador Z, Munafo MR, et al,. 2011. Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry 68: 675-690.
43. Lee BH, Kim YK,. 2010. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investig 7: 231-235.
44. Leonard B, Maes M,. 2012. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 36: 764-785.
45. Liu Y, Ho RC, Mak A,. 2012. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord 139: 230-239.
46. Lopresti AL, Maker GL, Hood SD, Drummond PD,. 2014. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry 48: 102-111.
47. Maes M, Galecki P, Chang YS, Berk M,. 2011. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 35: 676-692.
48. Maes M, Mihaylova I, Kubera M, Ringel K,. 2012a. Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression. Prog Neuropsychopharmacol Biol Psychiatry 36: 169-175.
49. Maes M, Zdenek F, Medina M, Scapagnini G, Nowak G, Berk M,. 2012b. New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates-Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology 20: 127-150.
50. Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russell J,. 2007. Neurobiology of depression: an integrated view of key findings. Int J Clin Pract 61: 2030-2040.
51. Matthes S, Mosienko V, Bashammakh S, Alenina N, Bader M,. 2010. Tryptophan hydroxylase as novel target for the treatment of depressive disorders. Pharmacology 85: 95-109.
52. Melnyk JP, Wang S, Marcone MF,. 2010. Chemical and biological properties of the world's most expensive spice: Saffron. Food Res Int 43: 1981-1989.
53. Modabbernia A, Sohrabi H, Nasehi AA, et al,. 2012. Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial. Psychopharmacology (Berl) 223: 381-388.
54. Modaghegh MH, Shahabian M, Esmaeili HA, Rajbai O, Hosseinzadeh H,. 2008. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers. Phytomedicine 15: 1032-1037.
55. Moghaddasi MS,. 2010. Saffron chemicals and medicine usage. J Med Plants Res 40: 427-430.
56. Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O, Hosseinzadeh H,. 2013. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci 16: 39-46.
57. Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S, Akhondzadeh S,. 2006. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine 13: 607-611.
58. Nam KN, Park YM, Jung HJ, et al,. 2010. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol 648: 110-116.
59. Newmaster SG, Grguric M, Shanmughanandhan D, Ramalingam S, Ragupathy S,. 2013. DNA barcoding detects contamination and substitution in North American herbal products. BMC Medicine 11: 222.
60. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH,. 2005. 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 97: 281-284.
61. Pace TW, Hu F, Miller AH,. 2007. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun 21: 9-19.
62. Palta P, Samuel LJ, Miller ER, 3rd, Szanton, SL,. 2014. Depression and oxidative stress: results from a meta-analysis of observational studies. Psychosom Med 76: 12-19.
63. Pariante CM, Lightman SL,. 2008. The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31: 464-468.
64. Piccardi M, Marangoni D, Minnella AM, et al,. 2012. A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function. Evid Based Complement Alternat Med 2012: 429124.
65. Poma A, Fontecchio G, Carlucci G, Chichiricco G,. 2012. Anti-inflammatory properties of drugs from saffron crocus. Antiinflamm Antiallergy Agents Med Chem 11: 37-51.
66. Raison CL, Miller AH,. 2011. Is depression an inflammatory disorder? Curr Psychiatry Rep 13: 467-475.
67. Raison CL, Capuron L, Miller AH,. 2006. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 27: 24-31.
68. Razavi BM, Hosseinzadeh H, Movassaghi AR, Imenshahidi M, Abnous K,. 2013. Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. Chem Biol Interact 203: 547-555.
69. Sadeghnia HR, Kamkar M, Assadpour E, Boroushaki MT, Ghorbani A,. 2013. Protective effect of safranal, a constituent of Crocus sativus, on quinolinic acid-induced oxidative damage in rat hippocampus. Iran J Basic Med Sci 16: 73-82.
70. Samarghandian S, Borji A, Delkhosh MB, Samini F,. 2013. Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. J Pharm Pharm Sci 16: 352-362.
71. Sampathu SR, Shivashankar S, Lewis YS, Wood AB,. 1984. Saffron (Crocus sativus Linn.)-cultivation, processing, chemistry and standardization. Cr Rev Food Sci 20: 123-157.
72. Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A,. 2011. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol 21: 841-860.
73. Schmidt M, Betti G, Hensel A,. 2007. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 157: 315-319.
74. Scholey A, Kennedy D, Wesnes K,. 2005. The psychopharmacology of herbal extracts: issues and challenges. Psychopharmacology (Berl) 179: 705-707; author reply 708-11.
75. Schulz KF, Altman DG, Moher D,. 2010. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med 152: 726-732.
76. Sen S, Duman R, Sanacora G,. 2008. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 64: 527-532.
77. Shahmansouri N, Farokhnia M, Abbasi SH, et al,. 2014. A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J Affect Disord 155: 216-222.
78. Shen XC, Qian ZY,. 2006. Effects of crocetin on antioxidant enzymatic activities in cardiac hypertrophy induced by norepinephrine in rats. Pharmazie 61: 348-352.
79. Tashakori-Sabzevar F, Hosseinzadeh H, Motamedshariaty VS, Movassaghi AR, Mohajeri SA,. 2013. Crocetin attenuates spatial learning dysfunction and hippocampal injury in a model of vascular dementia. Curr Neurovasc Res 10: 325-334.
80. Toker L, Amar S, Bersudsky Y, Benjamin J, Klein E, Agam G,. 2010. The biology of tryptophan depletion and mood disorders. Isr J Psychiatry Relat Sci 47: 46-55.
81. Vahdati Hassani F, Naseri V, Razavi BM, Mehri S, Abnous K, Hosseinzadeh H,. 2014. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. Daru 22: 16.
82. Valkanova V, Ebmeier KP, Allan CL,. 2013. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord 150: 736-744.
83. Wang Y, Han T, Zhu Y, et al,. 2010. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med 64: 24-30.
84. Wang Y, Yan J, Xi L, Qian Z, Wang Z, Yang L,. 2012. Protective effect of crocetin on hemorrhagic shock-induced acute renal failure in rats. Shock 38: 63-67.
85. Xu GL, Li G, Ma HP, Zhong H, Liu F, Ao GZ,. 2009. Preventive effect of crocin in inflamed animals and in LPS-challenged RAW 264.7 cells. J Agric Food Chem 57: 8325-8330.
86. Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM,. 2011. Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuropsychopharmacol Biol Psychiatry 35: 722-729.