Skip to content
2000
image of Crocus sativus and Neurological Health: A Review on Depression and Impaired Neurogenesis

Abstract

(saffron) is a valuable medicinal plant with a rich phytochemical profile, including bioactive carotenoids, flavonoids, and terpenoids. The key constituents of saffron, crocin, crocetin, picrocrocin, and safranal, exhibit potent neuroprotective properties, with crocin, a water-soluble carotenoid, plays a crucial role in promoting neurogenesis and mitigating depressive symptoms. Depression, affecting approximately 280 million individuals globally (WHO, 2023), is closely associated with impaired neurogenesis, highlighting the need for novel treatment strategies. , particularly in its nanotherapeutic form, shows promise in the treatment of depression by effectively crossing the blood-brain barrier and modulating neurotransmitter systems. In addition to its carotenoids, saffron contains flavonoids, such as kaempferol and quercetin derivatives, which contribute to its antioxidant and anti-inflammatory activities. This review explores the phytochemical composition of , its role in neurogenesis, and its potential as a therapeutic agent for depression and neurodegenerative disorders.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128380974250716232813
2025-08-05
2025-11-06

  • From This Site

    /content/journals/cpd/10.2174/0113816128380974250716232813
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Kumar A. Pareek V. Faiq M.A. Ghosh S.K. Kumari C. Adult neurogenesis in humans: A review of basic concepts, history, current research, and clinical implications. Innov. Clin. Neurosci. 2019 16 5-6 30 37 31440399
    [Google Scholar]
  2. Bian X. Yang W. Lin J. Jiang B. Shao X. Hypothalamic-pituitary-adrenal axis and epilepsy. J. Clin. Neurol. 2024 20 2 131 139 10.3988/jcn.2023.0308 38330420
    [Google Scholar]
  3. Hussain M.S. Gupta G. Samuel V.P. Immunopathology of herpes simplex virus‐associated neuroinflammation: Unveiling the mysteries. Rev. Med. Virol. 2024 34 1 e2491 10.1002/rmv.2491 37985599
    [Google Scholar]
  4. Horgusluoglu E. Nudelman K. Nho K. Saykin A.J. Adult neurogenesis and neurodegenerative diseases: A systems biology perspective. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 2017 174 1 93 112 10.1002/ajmg.b.32429
    [Google Scholar]
  5. Pariante C.M. Lightman S.L. The HPA axis in major depression: classical theories and new developments. Trends Neurosci. 2008 31 9 464 468 10.1016/j.tins.2008.06.006 18675469
    [Google Scholar]
  6. Young E.A. Haskett R.F. Murphy-Weinberg V. Watson S.J. Akil H. Loss of glucocorticoid fast feedback in depression. Arch. Gen. Psychiatry 1991 48 8 693 699 10.1001/archpsyc.1991.01810320017003 1652926
    [Google Scholar]
  7. Hussain M.S. Moglad E. Afzal M. Autophagy‐associated non‐coding RNAs: Unraveling their impact on Parkinson’s disease pathogenesis. CNS Neurosci. Ther. 2024 30 5 e14763 10.1111/cns.14763 38790149
    [Google Scholar]
  8. Lino de Oliveira C. Bolzan J.A. Surget A. Belzung C. Do antidepressants promote neurogenesis in adult hippocampus? A systematic review and meta-analysis on naive rodents. Pharmacol. Ther. 2020 210 107515 10.1016/j.pharmthera.2020.107515 32109488
    [Google Scholar]
  9. Siddiqui SA Ali Redha A Snoeck ER Anti-depressant properties of crocin molecules in saffron. molecules 2022 27 7 2076 10.3390/molecules27072076 35408474
    [Google Scholar]
  10. Abu-Izneid T. Rauf A. Khalil A.A. Nutritional and health beneficial properties of saffron (Crocus sativus L): a comprehensive review. Crit. Rev. Food Sci. Nutr. 2022 62 10 2683 2706 10.1080/10408398.2020.1857682 33327732
    [Google Scholar]
  11. Tóth B. Hegyi P. Lantos T. The efficacy of saffron in the treatment of mild to moderate depression: A meta-analysis. Planta Med. 2019 85 1 24 31 10.1055/a‑0660‑9565 30036891
    [Google Scholar]
  12. Javadi B. Sahebkar A. Emami S.A. A survey on saffron in major islamic traditional medicine books. Iran. J. Basic Med. Sci. 2013 16 1 1 11 23638288
    [Google Scholar]
  13. Yaribeygi H. Mohammadi M.T. Rezaee R. Sahebkar A. Crocin improves renal function by declining Nox‐4, IL‐18, and p53 expression levels in an experimental model of diabetic nephropathy. J. Cell. Biochem. 2018 119 7 6080 6093 10.1002/jcb.26806 29575259
    [Google Scholar]
  14. Yaribeygi H. Mohammadi M.T. Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed. Pharmacother. 2018 98 333 337 10.1016/j.biopha.2017.12.077
    [Google Scholar]
  15. Marx W. Lane M. Rocks T. Effect of saffron supplementation on symptoms of depression and anxiety: a systematic review and meta-analysis. Nutr. Rev. 2019 77 8 557 571 10.1093/nutrit/nuz023 31135916
    [Google Scholar]
  16. Roustazade R. Radahmadi M. Yazdani Y. Therapeutic effects of saffron extract on different memory types, anxiety, and hippocampal BDNF and TNF-α gene expressions in sub-chronically stressed rats. Nutr. Neurosci. 2022 25 1 192 206 10.1080/1028415X.2021.1943138 34165393
    [Google Scholar]
  17. Ayati Z. Yang G. Ayati M.H. Emami S.A. Chang D. Saffron for mild cognitive impairment and dementia: a systematic review and meta-analysis of randomised clinical trials. BMC Complementary Medicine and Therapies 2020 20 1 333 10.1186/s12906‑020‑03102‑3 33167948
    [Google Scholar]
  18. Cerdá-Bernad D. Costa L. Serra A.T. Saffron against neuro-cognitive disorders: An overview of its main bioactive compounds, their metabolic fate and potential mechanisms of neurological protection. Nutrients 2022 14 24 5368 10.3390/nu14245368 36558528
    [Google Scholar]
  19. Zandi N. Pazoki B. Momeni Roudsari N. Prospects of saffron and its derivatives in Alzheimer’s disease. Arch. Iran Med. 2021 24 3 233 252 10.34172/aim.2021.35 33878882
    [Google Scholar]
  20. Inoue E. Suzuki T. Shimizu Y. Sudo K. Kawasaki H. Ishida N. Saffron ameliorated motor symptoms, short life span and retinal degeneration in Parkinson’s disease fly models. Gene 2021 799 145811 10.1016/j.gene.2021.145811 34224829
    [Google Scholar]
  21. Pascual-Brazo J. Baekelandt V. Encinas J. Neurogenesis as a new target for the development of antidepressant drugs. Curr. Pharm. Des. 2014 20 23 3763 3775 10.2174/13816128113196660739 24180394
    [Google Scholar]
  22. Serafini G. Hayley S. Pompili M. Hippocampal neurogenesis, neurotrophic factors and depression: possible therapeutic targets? CNS Neurol. Disord. Drug Targets 2015 13 10 1708 1721 10.2174/1871527313666141130223723 25470403
    [Google Scholar]
  23. Deng W. Aimone J.B. Gage F.H. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 2010 11 5 339 350 10.1038/nrn2822 20354534
    [Google Scholar]
  24. Berton O. Nestler E.J. New approaches to antidepressant drug discovery: beyond monoamines. Nat. Rev. Neurosci. 2006 7 2 137 151 10.1038/nrn1846 16429123
    [Google Scholar]
  25. Bambico F.R. Belzung C. Novel insights into depression and antidepressants: a synergy between synaptogenesis and neurogenesis? Curr. Top. Behav. Neurosci. 2012 15 243 291 10.1007/7854_2012_234 23271325
    [Google Scholar]
  26. Hussain M.S. Chaturvedi V. Goyal S. Singh S. Mir R.H. An update on the application of nano phytomedicine as an emerging therapeutic tool for neurodegenerative diseases. Curr. Bioact. Compd. 2024 20 5 e251023222648 10.2174/0115734072258656231013085318
    [Google Scholar]
  27. Respondek M. Buszman E. Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain. Postepy Hig. Med. Dosw. 2015 69 1451 1461
    [Google Scholar]
  28. Jasoria Y. Agrawal M. Singhal M. Chaudhary H. Yadav M. Hussain M.S. Role of Exosomes in Multiple Sclerosis. Exosomes Based Drug Delivery Strategies for Brain Disorders. Springer 2024 103 121 10.1007/978‑981‑99‑8373‑5_4
    [Google Scholar]
  29. Baptista P. Andrade J.P. Adult Hippocampal neurogenesis: regulation and possible functional and clinical correlates. Front. Neuroanat. 2018 12 44 10.3389/fnana.2018.00044 29922131
    [Google Scholar]
  30. Benarroch E.E. Adult neurogenesis in the dentate gyrus. Neurology 2013 81 16 1443 1452 10.1212/WNL.0b013e3182a9a156 24078736
    [Google Scholar]
  31. Hussain S. Khan M.A. Rajan R. Jyoti J. Sharma S. Sahu S.K. Nanorobots: The future of healthcare. In: AIP Publishing 2023 2800 020171 10.1063/5.0162904
    [Google Scholar]
  32. Hanson N.D. Owens M.J. Nemeroff C.B. Depression, antidepressants, and neurogenesis: a critical reappraisal. Neuropsychopharmacology 2011 36 13 2589 2602 10.1038/npp.2011.220
    [Google Scholar]
  33. Kosar M Demirci B Goger F Kara I Baser KHC Volatile composition, antioxidant activity, and antioxidant components in saffron cultivated in Turkey. Int J Food Prop 2017 20 sup1 S746 54 10.1080/10942912.2017.1311341
    [Google Scholar]
  34. Ghanbari J. Khajoei-Nejad G. Erasmus S.W. van Ruth S.M. Identification and characterisation of volatile fingerprints of saffron stigmas and petals using PTR-TOF-MS: Influence of nutritional treatments and corm provenance. Ind. Crops Prod. 2019 141 111803 10.1016/j.indcrop.2019.111803
    [Google Scholar]
  35. Anastasaki E. Kanakis C. Pappas C. Geographical differentiation of saffron by GC–MS/FID and chemometrics. Eur. Food Res. Technol. 2009 229 6 899 905 10.1007/s00217‑009‑1125‑x
    [Google Scholar]
  36. Gohari A. Saeidnia S. Mahmoodabadi M. An overview on saffron, phytochemicals, and medicinal properties. Pharmacogn. Rev. 2013 7 1 61 66 10.4103/0973‑7847.112850 23922458
    [Google Scholar]
  37. Pandita D. Saffron (Crocus sativus L.): Phytochemistry, therapeutic significance and omics-based biology. Medicinal and aromatic plants. Medicinal and Aromatic Plants. Elsevier 2021 325 396
    [Google Scholar]
  38. Javan I.Y. Hosseinzadehgonabad Y. Isolation of main genes involved in flowering of Saffron (Crocus sativus L.) in order to study effective flowering protein. J. Food Sci. Eng. 2017 7 396 397
    [Google Scholar]
  39. Escribano J. Alonso G.L. Coca-Prados M. Fernández J.A. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett. 1996 100 1-2 23 30 10.1016/0304‑3835(95)04067‑6 8620447
    [Google Scholar]
  40. Trapero A. Ahrazem O. Rubio-Moraga A. Jimeno M.L. Gómez M.D. Gómez-Gómez L. Characterization of a glucosyltransferase enzyme involved in the formation of kaempferol and quercetin sophorosides in Crocus sativus. Plant Physiol. 2012 159 4 1335 1354 10.1104/pp.112.198069 22649274
    [Google Scholar]
  41. Hussain M.S. Altamimi A.S.A. Afzal M. Kaempferol: Paving the path for advanced treatments in aging-related diseases. Exp. Gerontol. 2024 188 112389 10.1016/j.exger.2024.112389 38432575
    [Google Scholar]
  42. Mottaghipisheh J. Mahmoodi Sourestani M. Kiss T. Comprehensive chemotaxonomic analysis of saffron crocus tepal and stamen samples, as raw materials with potential antidepressant activity. J. Pharm. Biomed. Anal. 2020 184 113183 10.1016/j.jpba.2020.113183 32105944
    [Google Scholar]
  43. Yılmaz E. Baltaci S.B. Mogulkoc R. Baltaci A.K. The impact of flavonoids and BDNF on neurogenic process in various physiological/pathological conditions including ischemic insults: a narrative review. Nutr. Neurosci. 2024 27 9 1025 1041 10.1080/1028415X.2023.2296165 38151886
    [Google Scholar]
  44. Yilmaz E. Acar G. Onal U. Erdogan E. Baltaci A.K. Mogulkoc R. Effect of 2-Week Naringin Supplementation on Neurogenesis and BDNF Levels in Ischemia–Reperfusion Model of Rats. Neuromolecular Med. 2024 26 1 4 10.1007/s12017‑023‑08771‑0 38457013
    [Google Scholar]
  45. Rubio-Moraga Á. Gerwig G.J. Castro-Díaz N. Triterpenoid saponins from corms of Crocus sativus: Localization, extraction and characterization. Ind. Crops Prod. 2011 34 3 1401 1409 10.1016/j.indcrop.2011.04.013
    [Google Scholar]
  46. Ali A. Yu L. Kousar S. Crocin: Functional characteristics, extraction, food applications and efficacy against brain related disorders. Front. Nutr. 2022 9 1009807 10.3389/fnut.2022.1009807 36583211
    [Google Scholar]
  47. Lamptey R.N.L. Chaulagain B. Trivedi R. Gothwal A. Layek B. Singh J. A review of the common neurodegenerative disorders: Current therapeutic approaches and the potential role of nanotherapeutics. Int. J. Mol. Sci. 2022 23 3 1851 10.3390/ijms23031851 35163773
    [Google Scholar]
  48. Milani A. Basirnejad M. Shahbazi S. Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. Br. J. Pharmacol. 2017 174 11 1290 1324 10.1111/bph.13625 27638711
    [Google Scholar]
  49. Scuto M. Modafferi S. Rampulla F. Redox modulation of stress resilience by Crocus sativus L. for potential neuroprotective and anti-neuroinflammatory applications in brain disorders: From molecular basis to therapy. Mech. Ageing Dev. 2022 205 111686 10.1016/j.mad.2022.111686 35609733
    [Google Scholar]
  50. Korani S. Korani M. Sathyapalan T. Sahebkar A. Therapeutic effects of Crocin in autoimmune diseases: A review. Biofactors 2019 45 6 835 843 10.1002/biof.1557 31430413
    [Google Scholar]
  51. Hussain M.S. Goyal A. Goyal K. Targeting CXCR2 signaling in inflammatory lung diseases: neutrophil-driven inflammation and emerging therapies. Naunyn Schmiedebergs Arch. Pharmacol. 2025 10.1007/s00210‑025‑03970‑x 40047857
    [Google Scholar]
  52. Barros M. Poppe S. Bondan E. Neuroprotective properties of the marine carotenoid astaxanthin and omega-3 fatty acids, and perspectives for the natural combination of both in krill oil. Nutrients 2014 6 3 1293 1317 10.3390/nu6031293 24667135
    [Google Scholar]
  53. Bahbah E.I. Ghozy S. Attia M.S. Molecular mechanisms of astaxanthin as a potential neurotherapeutic agent. Mar. Drugs 2021 19 4 201 10.3390/md19040201 33916730
    [Google Scholar]
  54. Noorbala A.A. Akhondzadeh S. Tahmacebi-Pour N. Jamshidi A.H. 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 2 281 284 10.1016/j.jep.2004.11.004 15707766
    [Google Scholar]
  55. Kashani L. Eslatmanesh S. Saedi N. Comparison of saffron versus fluoxetine in treatment of mild to moderate postpartum depression: a double-blind, randomized clinical trial. Pharmacopsychiatry 2017 50 2 64 68 27595298
    [Google Scholar]
  56. Dai L. Chen L. Wang W. Safety and Efficacy of Saffron (Crocus sativus L.) for Treating Mild to Moderate Depression. J. Nerv. Ment. Dis. 2020 208 4 269 276 10.1097/NMD.0000000000001118 32221179
    [Google Scholar]
  57. Monroe S.M. Anderson S.F. Harkness K.L. Life stress and major depression: The mysteries of recurrences. Psychol. Rev. 2019 126 6 791 816 10.1037/rev0000157 31414874
    [Google Scholar]
  58. Monroe S.M. Harkness K.L. Major depression and its recurrences: life course matters. Annu. Rev. Clin. Psychol. 2022 18 1 329 357 10.1146/annurev‑clinpsy‑072220‑021440 35216520
    [Google Scholar]
  59. Hosseinzadeh H. Karimi G. Niapoor M. Antidepressant effect of Crocus sativus L. stigma extracts and their constituents, crocin and safranal, in mice. International Symposium on Saffron Biology and Biotechnology 2004 650 54 435 45 10.17660/ActaHortic.2004.650.54
    [Google Scholar]
  60. Hosseinzadeh H. Jahanian Z. Effect of crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice. Phytother. Res. 2010 24 5 726 730 10.1002/ptr.3011 19827024
    [Google Scholar]
  61. Mokhtari-Zaer A. Saadat S. Ghorani V. Memarzia A. Boskabady M.H. The effects of saffron (Crocus sativus) and its constituents on immune system: experimental and clinical evidence. Saffron. Saffron. Elsevier 2020 193 217 10.1016/B978‑0‑12‑818462‑2.00016‑4
    [Google Scholar]
  62. Lu L. Wu D. Wang K. Tang J. Chen G. Beneficial effects of crocin against depression via pituitary adenylate cyclase‐activating polypeptide. BioMed Res. Int. 2020 2020 1 3903125 10.1155/2020/3903125 32685478
    [Google Scholar]
  63. Moragrega I. Ríos J.L. Medicinal plants in the treatment of depression: Evidence from preclinical studies. Planta Med. 2021 87 9 656 685 10.1055/a‑1338‑1011 33434941
    [Google Scholar]
  64. Chaudhury D. Liu H. Han M.H. Neuronal correlates of depression. Cell. Mol. Life Sci. 2015 72 24 4825 4848 10.1007/s00018‑015‑2044‑6 26542802
    [Google Scholar]
  65. Wang Y. Han T. Zhu Y. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J. Nat. Med. 2010 64 1 24 30 10.1007/s11418‑009‑0360‑6 19787421
    [Google Scholar]
  66. Siddiqui M. Saleh M.M. Basharuddin S.B.B. Saffron (Crocus sativus L.): As an antidepressant. J. Pharm. Bioallied Sci. 2018 10 4 173 180 10.4103/JPBS.JPBS_83_18 30568374
    [Google Scholar]
  67. Khan A. Muhamad N.A. Ismail H. Nasir A. Khalil A.A.K. Anwar Y. Potential nutraceutical benefits of in vivo saffron (Crocus sativus L.) as analgesic, anti-inflammatory, anticoagulant, and antidepressant in mice. Plants 2020 9 11 1414 10.3390/plants9111414
    [Google Scholar]
  68. Razaghi F. Zahiri A.S. Ataee R. Evaluation of antidepressant synergic effect of sativus crocus extract and fluoxetine in mice with swimming and tail suspension tests. SSU J 2018 26 518 527
    [Google Scholar]
  69. Kiashemshaki B. Safakhah H.A. Ghanbari A. Khaleghian A. Miladi-Gorji H. Saffron (Crocus sativus L.) stigma reduces symptoms of morphine-induced dependence and spontaneous withdrawal in rats. Am. J. Drug Alcohol Abuse 2021 47 2 170 181 10.1080/00952990.2020.1865995 33497577
    [Google Scholar]
  70. Ramírez J.M. Salazar J.J. Fernández-Albarral J.A. Beneficial effects of saffron (Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases. Neural Regen. Res. 2020 15 8 1408 1416 10.4103/1673‑5374.274325 31997799
    [Google Scholar]
  71. Moshiri E. Basti A.A. Noorbala A.A. Jamshidi A.H. Hesameddin Abbasi S. 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 10.1016/j.phymed.2006.08.006 16979327
    [Google Scholar]
  72. Hausenblas H.A. Saha D. Dubyak P.J. Anton S.D. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J. Integr. Med. 2013 11 6 377 383 10.3736/jintegrmed2013056 24299602
    [Google Scholar]
  73. Kanakis C.D. Tarantilis P.A. Pappas C. Bariyanga J. Tajmir-Riahi H.A. Polissiou M.G. An overview of structural features of DNA and RNA complexes with saffron compounds: Models and antioxidant activity. J. Photochem. Photobiol. B 2009 95 3 204 212 10.1016/j.jphotobiol.2009.03.006 19395270
    [Google Scholar]
  74. Kanakis C.D. Tarantilis P.A. Tajmir-Riahi H.A. Polissiou M.G. DNA interaction with saffron’s secondary metabolites safranal, crocetin, and dimethylcrocetin. DNA Cell Biol. 2007 26 1 63 70 10.1089/dna.2006.0529 17263598
    [Google Scholar]
  75. Kanakis C.D. Tarantilis P.A. Tajmir-Riahi H.A. Polissiou M.G. Interaction of tRNA with Safranal, Crocetin, and Dimethylcrocetin. J. Biomol. Struct. Dyn. 2007 24 6 537 545 10.1080/07391102.2007.10507142 17508775
    [Google Scholar]
  76. Pham T.Q. Cormier F. Farnworth E. Tong V.H. Van Calsteren M.R. Antioxidant properties of crocin from Gardenia jasminoides Ellis and study of the reactions of crocin with linoleic acid and crocin with oxygen. J. Agric. Food Chem. 2000 48 5 1455 1461 10.1021/jf991263j 10820042
    [Google Scholar]
  77. Akhondzadeh S. Fallah-Pour H. Afkham K. Jamshidi A.H. Khalighi-Cigaroudi F. 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 1 12 10.1186/1472‑6882‑4‑12 15341662
    [Google Scholar]
  78. Ghajar A. Neishabouri S. Velayati N. Crocus sativus L. versus citalopram in the treatment of major depressive disorder with anxious distress: A double-blind, controlled clinical trial. Pharmacopsychiatry 2017 50 4 152 160 10.1055/s‑0042‑116159 27701683
    [Google Scholar]
  79. Jafarnia N Ghorbani Z Nokhostin M Manayi A Nourimajd S Jahromi SR Effect of saffron (Crocus sativus L.) as an add-on therapy to sertraline in mild to moderate generalized anxiety disorder: a double blind randomized controlled trial. Arch Neurosci 2017 4 4 e14332 10.5812/archneurosci.14332
    [Google Scholar]
  80. Kriegstein A. Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells. Annu. Rev. Neurosci. 2009 32 1 149 184 10.1146/annurev.neuro.051508.135600 19555289
    [Google Scholar]
  81. Feliciano D.M. Bordey A. Bonfanti L. Noncanonical sites of adult neurogenesis in the mammalian brain. Cold Spring Harb. Perspect. Biol. 2015 7 10 a018846 10.1101/cshperspect.a018846 26384869
    [Google Scholar]
  82. Pardal R. López Barneo J. Mature neurons modulate neurogenesis through chemical signals acting on neural stem cells. Dev. Growth Differ. 2016 58 5 456 462 10.1111/dgd.12283 27101323
    [Google Scholar]
  83. Okano H. Sawamoto K. Neural stem cells: involvement in adult neurogenesis and CNS repair. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2008 363 1500 2111 2122 10.1098/rstb.2008.2264 18339601
    [Google Scholar]
  84. Azari H. Ebrahimi S. Saeb S. Ghanbari A. Peyravian F. Mokarram P. The effect of saffron aquatic extract and crocin on the differentiation of neural stem cells into oligodendrocyte precursor cells. Shiraz E Med. J. 2018 19 3 e60190 10.5812/semj.60190
    [Google Scholar]
  85. Liu Z. Wang Z. Zhu Z. Crocetin regulates functions of neural stem cells to generate new neurons for cerebral ischemia recovery. Adv. Healthc. Mater. 2023 12 20 2203132 10.1002/adhm.202203132 37001492
    [Google Scholar]
  86. Popoli M. Gennarelli M. Racagni G. Modulation of synaptic plasticity by stress and antidepressants. Bipolar Disord. 2002 4 3 166 182 10.1034/j.1399‑5618.2002.01159.x 12180272
    [Google Scholar]
  87. Matraszek-Gawron R. Chwil M. Terlecki K. Skoczylas M.M. Current knowledge of the antidepressant activity of chemical compounds from Crocus sativus L. Pharmaceuticals (Basel) 2022 16 1 58 10.3390/ph16010058 36678554
    [Google Scholar]
  88. Afridi R. Suk K. Microglial responses to stress-induced depression: causes and consequences. Cells 2023 12 11 1521 10.3390/cells12111521 37296642
    [Google Scholar]
  89. Park S.C. Neurogenesis and antidepressant action. Cell Tissue Res. 2019 377 1 95 106 10.1007/s00441‑019‑03043‑5 31165247
    [Google Scholar]
  90. Fang S. Wu Z. Guo Y. Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics. Front. Immunol. 2023 14 1193053 10.3389/fimmu.2023.1193053 37881439
    [Google Scholar]
  91. Chen X. Cui Q.Q. Hu X.H. CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation. J. Neuroinflammation 2023 20 1 157 10.1186/s12974‑023‑02836‑4 37391731
    [Google Scholar]
  92. Ettehadi H. Mojabi S.N. Ranjbaran M. Aqueous extract of saffron (Crocus sativus) increases brain dopamine and glutamate concentrations in rats. J. Behav. Brain Sci. 2013 3 3 315 319 10.4236/jbbs.2013.33031
    [Google Scholar]
  93. Garnier A. Shahidi F. Spices and herbs as immune enhancers and anti-inflammatory agents: a review. J. Food Bioact. 2021 14 20 52 10.31665/JFB.2021.14266
    [Google Scholar]
  94. Gudarzi S. Jafari M. Pirzad Jahromi G. Eshrati R. Asadollahi M. Nikdokht P. Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: a randomized clinical trial. Nutr. Neurosci. 2022 25 6 1137 1146 10.1080/1028415X.2020.1840118 33151132
    [Google Scholar]
  95. Bian Y. Zhao C. Lee S.M.Y. Neuroprotective potency of saffron against neuropsychiatric diseases, neurodegenerative diseases, and other brain disorders: From bench to bedside. Front. Pharmacol. 2020 11 579052 10.3389/fphar.2020.579052 33117172
    [Google Scholar]
  96. Kuzmov A. Minko T. Nanotechnology approaches for inhalation treatment of lung diseases. J. Control. Release 2015 219 500 518 10.1016/j.jconrel.2015.07.024
    [Google Scholar]
  97. Wang Z. Xiong G. Tsang W.C. Schätzlein A.G. Uchegbu I.F. Nose-to-brain delivery. J. Pharmacol. Exp. Ther. 2019 370 3 593 601 10.1124/jpet.119.258152 31126978
    [Google Scholar]
  98. Hussain M.S. Sharma P. Dhanjal D.S. Nanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseases. Chem. Biol. Interact. 2021 348 109637 10.1016/j.cbi.2021.109637 34506765
    [Google Scholar]
  99. Mirhadi E. Nassirli H. Malaekeh-Nikouei B. An updated review on therapeutic effects of nanoparticle-based formulations of saffron components (safranal, crocin, and crocetin). J. Pharm. Investig. 2020 50 1 47 58 10.1007/s40005‑019‑00435‑1
    [Google Scholar]
  100. Khameneh B. Halimi V. Jaafari M.R. Golmohammadzadeh S. Safranal-loaded solid lipid nanoparticles: evaluation of sunscreen and moisturizing potential for topical applications. Iran. J. Basic Med. Sci. 2015 18 1 58 63 25810877
    [Google Scholar]
  101. Puglia C. Santonocito D. Musumeci T. Nanotechnological approach to increase the antioxidant and cytotoxic efficacy of crocin and crocetin. Planta Med. 2019 85 3 258 265 10.1055/a‑0732‑5757 30206907
    [Google Scholar]
  102. Al Asmari A.K. Ullah Z. Tariq M. Fatani A. Preparation, characterization, and in vivo of intranasally administered liposomal formulation of donepezil. Drug Des. Devel. Ther. 2016 10 205 215 26834457
    [Google Scholar]
  103. Jaiswal M Dudhe R Sharma PK Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech 2015 5 2 123 7 10.1007/s13205‑014‑0214‑02
    [Google Scholar]
  104. Ray S. Cheng C.A. Chen W. Li Z. Zink J.I. Lin Y.Y. Magnetic heating stimulated cargo release with dose control using multifunctional mr and thermosensitive liposome. Nanotheranostics 2019 3 2 166 178 10.7150/ntno.31164 31183312
    [Google Scholar]
  105. Mohammadi-Samani S. Ghasemiyeh P. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res. Pharm. Sci. 2018 13 4 288 303 10.4103/1735‑5362.235156 30065762
    [Google Scholar]
  106. Singh S. Sharma N. Behl T. Promising strategies of colloidal drug delivery-based approaches in psoriasis management. Pharmaceutics 2021 13 11 1978 10.3390/pharmaceutics13111978 34834393
    [Google Scholar]
  107. Mukherjee S. Ray S. Thakur R.S. Solid lipid nanoparticles: A modern formulation approach in drug delivery system. Indian J. Pharm. Sci. 2009 71 4 349 358 10.4103/0250‑474X.57282 20502539
    [Google Scholar]
  108. Schmidt M. Betti G. Hensel A. Saffron in phytotherapy: Pharmacology and clinical uses. Wien. Med. Wochenschr. 2007 157 13-14 315 319 10.1007/s10354‑007‑0428‑4 17704979
    [Google Scholar]
  109. Ayatollahi H. Javan A.O. Khajedaluee M. Shahroodian M. Hosseinzadeh H. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytother. Res. 2014 28 4 539 543 10.1002/ptr.5021 23733488
    [Google Scholar]
  110. Mousavi B. Bathaie S.Z. Fadai F. Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia. Avicenna J. Phytomed. 2015 5 5 413 419 26468460
    [Google Scholar]
  111. Bidlack W.R. Casarett & Doull’s toxicology: the basic science of poisons. J. Am. Coll. Nutr. 2002 21 3 289 290 10.1080/07315724.2002.10719223
    [Google Scholar]
  112. Nair S.C. Kurumboor S.K. Hasegawa J.H. Saffron chemoprevention in biology and medicine: a review. Cancer Biother. 1995 10 4 257 264 10.1089/cbr.1995.10.257 8590890
    [Google Scholar]
  113. Hariri A.T. Moallem S.A. Mahmoudi M. Memar B. Hosseinzadeh H. Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: protective effects of crocin and safranal. Food Chem. Toxicol. 2010 48 10 2803 2808 10.1016/j.fct.2010.07.010
    [Google Scholar]
  114. Khorasany A.R. Hosseinzadeh H. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review. Iran. J. Basic Med. Sci. 2016 19 5 455 469 27403251
    [Google Scholar]
  115. Carradori S Chimenti P Fazzari M Granese A Angiolella L Antimicrobial activity, synergism and inhibition of germ tube formation by Crocus sativus -derived compounds against Candida spp. J Enzyme Inhib Med Chem 2016 31 sup2 189 93 10.1080/14756366.2016.1180596 27160150
    [Google Scholar]
  116. Chrastina M. Dráfi F. Pružinská K. Crocus sativus L. extract (saffron) effectively reduces arthritic and inflammatory parameters in monotherapy and in combination with methotrexate in adjuvant arthritis. Nutrients 2023 15 19 4108 10.3390/nu15194108 37836391
    [Google Scholar]
  117. Monchaux De Oliveira C. Pourtau L. Vancassel S. Saffron extract-induced improvement of depressive-like behavior in mice is associated with modulation of monoaminergic neurotransmission. Nutrients 2021 13 3 904 10.3390/nu13030904 33799507
    [Google Scholar]
  118. Ghaffari S. Roshanravan N. Saffron; An updated review on biological properties with special focus on cardiovascular effects. Biomed. Pharmacother. 2019 109 21 27 10.1016/j.biopha.2018.10.031
    [Google Scholar]
  119. Sharma B. Kumar H. Kaushik P. Mirza R. Awasthi R. Kulkarni G. Therapeutic benefits of saffron in brain diseases: New lights on possible pharmacological mechanisms. In: Elsevier 2020 117 130 10.1016/B978‑0‑12‑818462‑2.00010‑3
    [Google Scholar]
  120. Alonso G. Zalacain A. Carmona M. Saffron. In: Handbook of herbs and spices. Elsevier 2012 469 498 10.1533/9780857095671.469
    [Google Scholar]
  121. Hussain M.S. Gupta G. Goyal A. From nature to therapy: Luteolin’s potential as an immune system modulator in inflammatory disorders. J. Biochem. Mol. Toxicol. 2023 37 11 e23482 10.1002/jbt.23482 37530602
    [Google Scholar]
  122. Mazidi M. Shemshian M. Mousavi S.H. A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression. J. Complement. Integr. Med. 2016 13 2 195 199 10.1515/jcim‑2015‑0043 27101556
    [Google Scholar]
  123. Asbaghi O. Sadeghian M. Sadeghi O. Effects of saffron (Crocus sativus L.) supplementation on inflammatory biomarkers: A systematic review and meta‐analysis. Phytother. Res. 2021 35 1 20 32 10.1002/ptr.6748 32525606
    [Google Scholar]
  124. Akbari-Fakhrabadi M. Najafi M. Mortazavian S. Rasouli M. Memari A.H. Shidfar F. Effect of saffron (Crocus sativus L.) and endurance training on mitochondrial biogenesis, endurance capacity, inflammation, antioxidant, and metabolic biomarkers in Wistar rats. J. Food Biochem. 2019 43 8 e12946 10.1111/jfbc.12946 31368566
    [Google Scholar]
  125. Akhondzadeh Basti A. Moshiri E. Noorbala A.A. Jamshidi A.H. Abbasi S.H. Akhondzadeh S. 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 2 439 442 10.1016/j.pnpbp.2006.11.010 17174460
    [Google Scholar]
  126. Kashani L. Esalatmanesh S. Eftekhari F. Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial. Arch. Gynecol. Obstet. 2018 297 3 717 724 10.1007/s00404‑018‑4655‑2 29332222
    [Google Scholar]
  127. Moosavi S.M. Ahmadi M. Amini M. Vazirzadeh B. The effects of 40 and 80 mg hydro-alcoholic extract of Crocus sativus in the treatment of mild to moderate depression. J. Mazandaran Univ. Med. Sci. 2014 24 48 53
    [Google Scholar]
  128. Tabeshpour J. Sobhani F. Sadjadi S.A. A double-blind, randomized, placebo-controlled trial of saffron stigma (Crocus sativus L.) in mothers suffering from mild-to-moderate postpartum depression. Phytomedicine 2017 36 145 152 10.1016/j.phymed.2017.10.005 29157808
    [Google Scholar]
  129. Shahmansouri N. Farokhnia M. Abbasi S.H. 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. 2014 155 216 222 10.1016/j.jad.2013.11.003 24289892
    [Google Scholar]
  130. Abedimanesh N. Ostadrahimi A. Bathaie S.Z. Effects of saffron aqueous extract and its main constituent, crocin, on health-related quality of life, depression, and sexual desire in coronary artery disease patients: a double-blind, placebo-controlled, randomized clinical trial. Iran. Red Crescent Med. J. 2017 19 9 19 10.5812/ircmj.13676
    [Google Scholar]
  131. Agha-Hosseini M. Kashani L. Aleyaseen A. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double‐blind, randomised and placebo‐controlled trial. BJOG 2008 115 4 515 519 10.1111/j.1471‑0528.2007.01652.x 18271889
    [Google Scholar]
  132. Jam I.N. Sahebkar A.H. Eslami S. Mokhber N. Nosrati M. Khademi M. The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Advances in clinical and experimental medicine: official organ Wroclaw. Med Univ 2017 26 925 930
    [Google Scholar]
  133. Jelodar G. Javid Z. Sahraian A. Jelodar S. Saffron improved depression and reduced homocysteine level in patients with major depression: A Randomized, double-blind study. Avicenna J. Phytomed. 2018 8 1 43 50 29387573
    [Google Scholar]
  134. Lopresti A.L. Drummond P.D. Inarejos-García A.M. Prodanov M. affron®, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study. J. Affect. Disord. 2018 232 349 357 10.1016/j.jad.2018.02.070 29510352
    [Google Scholar]
  135. Modabbernia A. Sohrabi H. Nasehi A.A. Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial. Psychopharmacology (Berl.) 2012 223 4 381 388 10.1007/s00213‑012‑2729‑6 22552758
    [Google Scholar]
  136. Sahraian A. Jelodar S. Javid Z. Mowla A. Ahmadzadeh L. Study the effects of saffron on depression and lipid profiles: A double blind comparative study. Asian J. Psychiatr. 2016 22 174 176 10.1016/j.ajp.2015.10.012 26611571
    [Google Scholar]
  137. Talaei A. Hassanpour Moghadam M. Sajadi Tabassi S.A. Mohajeri S.A. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. J. Affect. Disord. 2015 174 51 56 10.1016/j.jad.2014.11.035 25484177
    [Google Scholar]
  138. Khalatbari-mohseni A. Banafshe H.R. Mirhosseini N. Asemi Z. Ghaderi A. Omidi A. The effects of crocin on psychological parameters in patients under methadone maintenance treatment: a randomized clinical trial. Subst. Abuse Treat. Prev. Policy 2019 14 1 9 10.1186/s13011‑019‑0198‑1 30795785
    [Google Scholar]
  139. Moghadam B.H. Bagheri R. Roozbeh B. Impact of saffron (Crocus sativus Linn) supplementation and resistance training on markers implicated in depression and happiness levels in untrained young males. Physiol. Behav. 2021 233 113352 10.1016/j.physbeh.2021.113352 33556410
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128380974250716232813
Loading
Crocus sativus and Neurological Health: A Review on Depression and Impaired Neurogenesis
Bentham Science Publishers ; https://doi.org/10.2174/0113816128380974250716232813
/content/journals/cpd/10.2174/0113816128380974250716232813
/content/journals/cpd/10.2174/0113816128380974250716232813
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Crocin ; depression ; safranal ; crocetin ; saffron ; neurogenesis

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test