Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Neuroprotective Potency of Safranal Against Neurological Disorders

Author(s): Elham Fazeli, Mohammad Hossein Eshaghi Ghalibaf and Fatemeh Forouzanfar*

Volume 23, Issue 9, 2023

Published on: 19 December, 2022

Page: [952 - 959] Pages: 8

DOI: 10.2174/1566524023666221117104612

Price: $65

Abstract

A great number of research has been focused on plants as a source of medicine against many diseases to overcome the many side effects of chemical drugs. Safranal, one of the main constituents of saffron [Crocus sativus], has a broad spectrum of pharmacological effects, including anti-inflammatory, antioxidant, and antiapoptotic effects. The present review elaborates on the current understanding of the neuroprotective effects of safranal. According to data published so far, safranal has the potential to exert neuroprotective effects in neurological disorders such as epilepsy, stroke, multiple sclerosis, Parkinson, and Alzheimer’s disease. Safranal could be considered a promising therapeutic agent in the future, although there is a great need for clinical trial studies.

« Previous Next »
[1]
Feigin VL, Nichols E, Alam T, et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18(5): 459-80.
[http://dx.doi.org/10.1016/S1474-4422(18)30499-X] [PMID: 30879893]
[2]
Feigin VL, Vos T, Alahdab F, et al. Burden of neurological disorders across the US from 1990-2017: a global burden of disease study. JAMA Neurol 2021; 78(2): 165-76.
[http://dx.doi.org/10.1001/jamaneurol.2020.4152] [PMID: 33136137]
[3]
Caglayan C, Kandemir FM, Ayna A, Gür C, Küçükler S, Darendelioğlu E. Neuroprotective effects of 18β-glycyrrhetinic acid against bisphenol A-induced neurotoxicity in rats: involvement of neuronal apoptosis, endoplasmic reticulum stress and JAK1/STAT1 signaling pathway. Metab Brain Dis 2022; 37(6): 1931-40.
[http://dx.doi.org/10.1007/s11011-022-01027-z] [PMID: 35699857]
[4]
Gulcin İ. Antioxidants and antioxidant methods: an updated overview. Arch Toxicol 2020; 94(3): 651-715.
[http://dx.doi.org/10.1007/s00204-020-02689-3] [PMID: 32180036]
[5]
Cragg GM, Newman DJ. Natural products: A continuing source of novel drug leads. Biochim Biophys Acta, Gen Subj 2013; 1830(6): 3670-95.
[http://dx.doi.org/10.1016/j.bbagen.2013.02.008] [PMID: 23428572]
[6]
Che CT, Zhang H. Plant natural products for human health. Int J Mol Sci 2019; 20(4): 830.
[http://dx.doi.org/10.3390/ijms20040830] [PMID: 30769917]
[7]
Dogra A, Kotwal P, Gour A, et al. Description of druglike properties of safranal and its chemistry behind low oral exposure. ACS Omega 2020; 5(17): 9885-91.
[http://dx.doi.org/10.1021/acsomega.0c00160] [PMID: 32391475]
[8]
Mykhailenko O, Petrikaitė V, Korinek M, et al. Bio-guided bioactive profiling and HPLC-DAD fingerprinting of Ukrainian saffron (Crocus sativus stigmas): moving from correlation toward causation. BMC Complement Altern Med 2021; 21(1): 203.
[http://dx.doi.org/10.1186/s12906-021-03374-3] [PMID: 34289850]
[9]
Ramírez JM, Salazar JJ, Fernández-Albarral JA, et al. Beneficial effects of saffron (Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases. Neural Regen Res 2020; 15(8): 1408-16.
[http://dx.doi.org/10.4103/1673-5374.274325] [PMID: 31997799]
[10]
Ghaffari S, Roshanravan N. Saffron; An updated review on biological properties with special focus on cardiovascular effects. Biomed Pharmacother 2019; 109: 21-7.
[http://dx.doi.org/10.1016/j.biopha.2018.10.031] [PMID: 30391705]
[11]
Cerdá-Bernad D, Valero-Cases E, Pastor JJ, Frutos MJ. Saffron bioactives crocin, crocetin and safranal: effect on oxidative stress and mechanisms of action. Crit Rev Food Sci Nutr 2022; 62(12): 3232-49.
[http://dx.doi.org/10.1080/10408398.2020.1864279] [PMID: 33356506]
[12]
Abu-Izneid T, Rauf A, Khalil AA, Olatunde A, Khalid A, Alhumaydhi FA, et al. Nutritional and health beneficial properties of saffron (Crocus sativus L): a comprehensive review. Crit Rev Food Sci Nutr 2020; 1-24.
[PMID: 33327732]
[13]
Rasi Marzabadi L, Fazljou SMB, Araj-Khodaei M, Sadigh-Eteghad S, Naseri A, Talebi M. Saffron reduces some inflammation and oxidative stress markers in donepezil-treated mild-to-moderate Alzheimer’s Disease patients: A randomized double-blind placebo-control trial. J Herb Med 2022; 34: 100574.
[http://dx.doi.org/10.1016/j.hermed.2022.100574]
[14]
Papandreou MA, Tsachaki M, Efthimiopoulos S, Cordopatis P, Lamari FN, Margarity M. Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection. Behav Brain Res 2011; 219(2): 197-204.
[http://dx.doi.org/10.1016/j.bbr.2011.01.007] [PMID: 21238492]
[15]
Vanaei S, Parizi MS, Abdolhosseini S, Katouzian I. Spectroscopic, molecular docking and molecular dynamic simulation studies on the complexes of beta-lactoglobulin, safranal and oleuropein. Int J Biol Macromol 2020; 165(Pt B): 2326-7.
[16]
Pitsikas N. Crocus sativus L. Extracts and its constituents crocins and safranal; potential candidates for schizophrenia treatment? Molecules 2021; 26(5): 1237.
[http://dx.doi.org/10.3390/molecules26051237] [PMID: 33669124]
[17]
Mentis AFA, Dalamaga M, Lu C, Polissiou MG. Saffron for “toning down” COVID-19-related cytokine storm: Hype or hope? A mini-review of current evidence. Metabolism Open 2021; 11: 100111.
[http://dx.doi.org/10.1016/j.metop.2021.100111] [PMID: 34312610]
[18]
García-Blázquez A, Moratalla-López N, Lorenzo C, Salinas MR, Alonso GL. Effect of Crocus sativus L. Stigmas microwave dehydration on picrocrocin, safranal and crocetin esters. Foods 2021; 10(2): 404.
[http://dx.doi.org/10.3390/foods10020404] [PMID: 33673099]
[19]
Rezaee R, Hosseinzadeh H. Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci 2013; 16(1): 12-26.
[PMID: 23638289]
[20]
Alayunt ÖN, Aksoy L, Karafakioğlu YS, Sevimli S. Assessment of anti-inflammatory and antioxidant properties of safranal on CCI4-induced oxidative stress and inflammation in rats. An Acad Bras Cienc 2019; 91(2): e20181235.
[http://dx.doi.org/10.1590/0001-3765201920181235] [PMID: 31141017]
[21]
Shahat AS, Hassan WA, El-Sayed WM. N-Acetylcysteine and Safranal prevented the brain damage induced by hyperthyroidism in adult male rats. Nutr Neurosci 2022; 25(2): 231-45.
[http://dx.doi.org/10.1080/1028415X.2020.1743917] [PMID: 32264788]
[22]
Jabini R, Ehtesham-Gharaee M, Dalirsani Z, Mosaffa F, Delavarian Z, Behravan J. Evaluation of the cytotoxic activity of crocin and safranal, constituents of saffron, in oral squamous cell carcinoma (KB Cell Line). Nutr Cancer 2017; 69(6): 911-9.
[http://dx.doi.org/10.1080/01635581.2017.1339816] [PMID: 28718677]
[23]
Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia 2005; 76(7-8): 722-4.
[http://dx.doi.org/10.1016/j.fitote.2005.07.008] [PMID: 16253437]
[24]
Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, 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.
[http://dx.doi.org/10.1186/1472-6882-4-12] [PMID: 15341662]
[25]
Pitsikas N. Constituents of Saffron (Crocus sativus L.) as Potential Candidates for the Treatment of Anxiety Disorders and Schizophrenia. Molecules 2016; 21(3): 303.
[http://dx.doi.org/10.3390/molecules21030303] [PMID: 26950102]
[26]
Erfanparast A, Tamaddonfard E, Taati M, Dabbaghi M. Effects of crocin and safranal, saffron constituents, on the formalin-induced orofacial pain in rats. Avicenna J Phytomed 2015; 5(5): 392-402.
[PMID: 26468458]
[27]
Zhang C, Ma J, Fan L, et al. Neuroprotective effects of safranal in a rat model of traumatic injury to the spinal cord by anti-apoptotic, anti-inflammatory and edema-attenuating. Tissue Cell 2015; 47(3): 291-300.
[http://dx.doi.org/10.1016/j.tice.2015.03.007] [PMID: 25891268]
[28]
Pan P-K, Qiao L-Y, Wen X-N. Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson’s disease through regulating Keap1/Nrf2 signaling pathway. Cell Mol Biol 2016; 62(14): 11-7.
[http://dx.doi.org/10.14715/cmb/2016.62.14.2] [PMID: 28145852]
[29]
Bo-Qiang L, Si-Tong Z, Zu-Yuan L, et al. Safranal carried by nanostructured lipid vehicles inhibits generalized epilepsy in mice. Pharmazie 2018; 73(4): 207-12.
[PMID: 29609687]
[30]
Yilmaz U. Alzheimer-Demenz. Radiologe 2015; 55(5): 386-8.
[http://dx.doi.org/10.1007/s00117-014-2796-2] [PMID: 25957008]
[31]
Baluchnejadmojarad T, Mohamadi-Zarch SM, Roghani M. Safranal, an active ingredient of saffron, attenuates cognitive deficits in amyloid β-induced rat model of Alzheimer’s disease: underlying mechanisms. Metab Brain Dis 2019; 34(6): 1747-59.
[http://dx.doi.org/10.1007/s11011-019-00481-6] [PMID: 31422512]
[32]
Delkhosh-Kasmaie F, Farshid AA, Tamaddonfard E, Imani M. The effects of safranal, a constitute of saffron, and metformin on spatial learning and memory impairments in type-1 diabetic rats: behavioral and hippocampal histopathological and biochemical evaluations. Biomed Pharmacother 2018; 107: 203-11.
[http://dx.doi.org/10.1016/j.biopha.2018.07.165] [PMID: 30092399]
[33]
Asadpour E, Sadeghnia HR. Effect of safranal, a constituent of crocus sativus, on MK-801-induced behavioral and memory deficits in rat. Eur Psychiatry 2011; 26(S2): 1342.
[http://dx.doi.org/10.1016/S0924-9338(11)73047-4]
[34]
Rafieipour F, Hadipour E, Emami SA, Asili J, Tayarani-Najaran Z. Safranal protects against beta-amyloid peptide-induced cell toxicity in PC12 cells via MAPK and PI3 K pathways. Metab Brain Dis 2019; 34(1): 165-72.
[http://dx.doi.org/10.1007/s11011-018-0329-9] [PMID: 30402809]
[35]
Aldape K, Brindle KM, Chesler L, et al. Challenges to curing primary brain tumours. Nat Rev Clin Oncol 2019; 16(8): 509-20.
[http://dx.doi.org/10.1038/s41571-019-0177-5] [PMID: 30733593]
[36]
Farahzad JA, Samarghandian S, Shoshtari ME, Sargolzaei J, Hossinimoghadam H. Anti-tumor activity of safranal against neuroblastoma cells. Pharmacogn Mag 2014; 10(38) (Suppl. 2): 419.
[http://dx.doi.org/10.4103/0973-1296.133296] [PMID: 24991121]
[37]
Fisher RS, Boas WE, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the international league against epilepsy (ILAE) and the international bureau for epilepsy (IBE). Epilepsia 2005; 46(4): 470-2.
[http://dx.doi.org/10.1111/j.0013-9580.2005.66104.x] [PMID: 15816939]
[38]
Hosseinzadeh H, Sadeghnia HR. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems. Phytomedicine 2007; 14(4): 256-62.
[http://dx.doi.org/10.1016/j.phymed.2006.03.007] [PMID: 16707256]
[39]
Sadeghnia H, Cortez M, Liu D, Hosseinzadeh H, Snead OC III. Antiabsence effects of safranal in acute experimental seizure models: EEG and autoradiography. J Pharm Pharm Sci 2008; 11(3): 1-14.
[http://dx.doi.org/10.18433/J38G6J] [PMID: 18801302]
[40]
Bonomo R, Elia AE, Bonomo G, et al. Deep brain stimulation in Huntington’s disease: a literature review. Neurol Sci 2021; 42(11): 4447-57.
[http://dx.doi.org/10.1007/s10072-021-05527-1] [PMID: 34471947]
[41]
Fotoohi A, Moloudi MR, Hosseini S, Hassanzadeh K, Feligioni M, Izadpanah E. A novel pharmacological protective role for safranal in an animal model of Huntington’s disease. Neurochem Res 2021; 46(6): 1372-9.
[http://dx.doi.org/10.1007/s11064-021-03271-8] [PMID: 33611726]
[42]
Yang G, Van Kaer L. Therapeutic targeting of immune cell autophagy in multiple sclerosis: russian roulette or silver bullet? Front Immunol 2021; 12: 724108.
[http://dx.doi.org/10.3389/fimmu.2021.724108] [PMID: 34531871]
[43]
Doshi A, Chataway J. Multiple sclerosis, a treatable disease. Clin Med (Lond) 2016; 16 (Suppl. 6): s53-9.
[http://dx.doi.org/10.7861/clinmedicine.16-6-s53] [PMID: 27956442]
[44]
Alavi MS, Fanoudi S, Fard AV, et al. Safranal attenuates excitotoxin-induced oxidative OLN-93 cells injury. Drug Res (Stuttg) 2019; 69(6): 323-9.
[http://dx.doi.org/10.1055/a-0790-8200] [PMID: 30463091]
[45]
Sadeghnia HR, Kamkar M, Assadpour E, Boroushaki MT, Ghorbani A. Protective effect of safranal, a constituent of crocus sativus, on quinolinic acid-induced oxidative damage in rat hippocampus. Iran J Basic Med Sci 2013; 16(1): 73-82.
[PMID: 23638295]
[46]
Rakhshandeh H, Ghorbanzadeh A, Negah SS, Akaberi M, Rashidi R, Forouzanfar F. Pain-relieving effects of Lawsonia inermis on neuropathic pain induced by chronic constriction injury. Metab Brain Dis 2021; 36(7): 1709-16.
[http://dx.doi.org/10.1007/s11011-021-00773-w] [PMID: 34169409]
[47]
Bernetti A, Agostini F, de Sire A, et al. Neuropathic pain and rehabilitation: A systematic review of international guidelines. Diagnostics (Basel) 2021; 11(1): 74.
[http://dx.doi.org/10.3390/diagnostics11010074] [PMID: 33466426]
[48]
Amin B, Hosseinzadeh H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia 2012; 83(5): 888-95.
[http://dx.doi.org/10.1016/j.fitote.2012.03.022] [PMID: 22484092]
[49]
Zhu KJ, Yang JS. Anti-allodynia effect of safranal on neuropathic pain induced by spinal nerve transection in rat. Int J Clin Exp Med 2014; 7(12): 4990-6.
[PMID: 25663997]
[50]
Farshid AA, Tamaddonfard E. Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats. Avicenna J Phytomed 2015; 5(5): 469-78.
[PMID: 26468467]
[51]
Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol 2020; 27(1): 27-42.
[http://dx.doi.org/10.1111/ene.14108] [PMID: 31631455]
[52]
Zhao Y, Xi G. Safranal-promoted differentiation and survival of dopaminergic neurons in an animal model of Parkinson’s disease. Pharm Biol 2018; 56(1): 450-4.
[http://dx.doi.org/10.1080/13880209.2018.1501705] [PMID: 30354840]
[53]
Pourmohammadi-Bejarpasi Z, Roushandeh AM, Saberi A, et al. Mesenchymal stem cells-derived mitochondria transplantation mitigates I/R-induced injury, abolishes I/R-induced apoptosis, and restores motor function in acute ischemia stroke rat model. Brain Res Bull 2020; 165: 70-80.
[http://dx.doi.org/10.1016/j.brainresbull.2020.09.018] [PMID: 33010349]
[54]
Phipps MS, Cronin CA. Management of acute ischemic stroke. BMJ 2020; 368: l6983.
[http://dx.doi.org/10.1136/bmj.l6983] [PMID: 32054610]
[55]
Forouzanfar F, Shojapour M, Asgharzade S, Amini E. Causes and consequences of microRNA dysregulation following cerebral ischemia-reperfusion injury. CNS Neurol Disord-Drug Targets 2019; 18(3): 212.
[http://dx.doi.org/10.2174/1871527318666190204104629]
[56]
Sadeghnia HR, Shaterzadeh H, Forouzanfar F, Hosseinzadeh H. Neuroprotective effect of safranal, an active ingredient of Crocus sativus, in a rat model of transient cerebral ischemia. Folia Neuropathol 2017; 3(3): 206-13.
[http://dx.doi.org/10.5114/fn.2017.70485] [PMID: 28984113]
[57]
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(3): 394-9.
[PMID: 16401389]
[58]
Forouzanfar F, Asadpour E, Hosseinzadeh H, et al. Safranal protects against ischemia-induced PC12 cell injury through inhibiting oxidative stress and apoptosis. Naunyn Schmiedebergs Arch Pharmacol 2021; 394(4): 707-16.
[http://dx.doi.org/10.1007/s00210-020-01999-8] [PMID: 33128592]
[59]
Nakajima Y, Osuka K, Seki Y, et al. Taurine reduces inflammatory responses after spinal cord injury. J Neurotrauma 2010; 27(2): 403-10.
[http://dx.doi.org/10.1089/neu.2009.1044] [PMID: 19831872]
[60]
Shen H, Fan C, You Z, Xiao Z, Zhao Y, Dai J. Advances in biomaterial‐based spinal cord injury repair. Adv Funct Mater 2022; 32(13): 2110628.
[http://dx.doi.org/10.1002/adfm.202110628]
[61]
Chen Z, Zhong C. Oxidative stress in Alzheimer’s disease. Neurosci Bull 2014; 30(2): 271-81.
[http://dx.doi.org/10.1007/s12264-013-1423-y] [PMID: 24664866]
[62]
Khazipov R. GABAergic synchronization in epilepsy. Cold Spring Harb Perspect Med 2016; 6(2): a022764.
[http://dx.doi.org/10.1101/cshperspect.a022764] [PMID: 26747834]
[63]
Cardin JA. Inhibitory interneurons regulate temporal precision and correlations in cortical circuits. Trends Neurosci 2018; 41(10): 689-700.
[http://dx.doi.org/10.1016/j.tins.2018.07.015] [PMID: 30274604]
[64]
Asgharzade S, Talaei A, Farkhondeh T, Forouzanfar F. A review on stem cell therapy for neuropathic pain. Curr Stem Cell Res Ther 2020; 15(4): 349-61.
[http://dx.doi.org/10.2174/1574888X15666200214112908] [PMID: 32056531]
[65]
Forouzanfar F, Hosseinzadeh H, Khorrami MB, Asgharzade S, Rakhshandeh H. Attenuating effect of Portulaca oleracea extract on chronic constriction injury induced neuropathic pain in rats: an evidence of anti-oxidative and anti-inflammatory effects. CNS Neurol Disord-Drug Targets 2019; 18(4): 342-9.
[http://dx.doi.org/10.2174/1871527318666190314110528]
[66]
Sacerdote P, Franchi S, Moretti S, et al. Cytokine modulation is necessary for efficacious treatment of experimental neuropathic pain. J Neuroimmune Pharmacol 2013; 8(1): 202-11.
[http://dx.doi.org/10.1007/s11481-012-9428-2] [PMID: 23242694]
[67]
Rodrigo R, Fernandez-Gajardo R, Gutierrez R, Manuel Matamala J, Carrasco R, Miranda-Merchak A, et al. Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. CNS Neurol Disord-Drug Targets 2013; 12(5): 698-714.
[http://dx.doi.org/10.2174/1871527311312050015]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy