Safranal: From an Aromatic Natural Product to a Rewarding Pharmacological Agent

Document Type : Review Article

Authors

1 Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, I.R. Iran

2 Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Safranal, the main component of Crocus sativus essential oil, is thought to be the main cause of saffron unique odor. It is now about eighty years that this compound has been discovered and since then different scientific experiments have been done investigating its biological-pharmacological activities. Safranal effects in CNS have been more attractive to scientists and an escalating number of papers have been published regarding its neuropsychological effects. These promising properties of safranal propose its presence as a therapeutic agent in future, although there is a great need for further clinical trials and toxicological studies. In this review article, according to Scopus ®, Thomson Reuters Web of Knowledge®, Scientific Information Database (SID) ® and Pubmed ® all papers published until July 2012 were thoroughly discussed and a brief note of each study was prepared.

Keywords

References

  1. Zargari A. Medicinal Plants. Tehran: Tehran University Press; 1990.p.574-578.
  2. Hosseinzadeh H, Khosravan V. Anticonvulsant effects of aqueous and ethanolic extracts of crocus sativus l. Stigmas in mice. Arch Irn Med 2002; 5:44-447.
  3. Hosseinzadeh H, Karimi G, Niapoor M. Antidepressant effects of Crocus sativus stigma extracts and its constituents, crocin and safranal, in mice. Acta Hortic 2004; 650:435–445.
  4. Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol 2002; 15:2-7.
  5. Hosseinzadeh H, Shamsaie F, Soghra M. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituent, crocin and safranal. Pharmacogn Mag 2009; 5:419-424.
  6. Geromichalos GD, Lamari FN, Papandreou MA, Trafalis DT, Margarity M, Papageorgiou A, et al. Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies. J Agric Food Chem 2012; 60:6131-6138.
  7. Hosseinzadeh H, Ghenaati J. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia 2006; 77:446–448.
  8. 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; 24:726-730.
  9. 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.
  10.  Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA. 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.
  11.  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.
  12.  Golmohammadzadeh Sh, Jaafari MR, Hosseinzadeh H. Does saffron have antisolar and moisturizing effects? Iran J Pharm Res 2010; 9:133-140.
  13.  Bathaie SZ, Mousavi SZ. New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr  2010; 50:761-786.
  14.  Melnyk JP, Wang S, Marcone MF. Chemical and biological properties of the world's most expensive spice: Saffron. Food Res Int  2010; 43:1981-1989.
  15.  Giaccio M. Crocetin from saffron: an active component of an ancient spice. Crit Rev Food Sci Nutr  2004; 44:155–172.
  16.  MerckIndex. 14th ed. Merck & Co. INC, Whitehouse Station, NJ: 2006.
  17.  Alonso GL, Salinas MR, Esteban-Infantes FJ, Sanchez-Fernandez MA. Determination of safranal from saffron (Crocus sativus L.) by thermal desorption-gas chromatography. J Agric Food Chem  1996; 44:185–188.
  18.  Tarantilis PA, Polissiou M. Isolation and identification of the aroma components from saffron (Crocus sativus L.). J Agric Food Chem 1997; 45:459–462.
  19.  Zarghami NS, Heinz DE. The volatile constituents of saffron. Lebenson Wisenschaft Technol1971; 4:43–45.
  20.  Himeno H, Sano K. Synthesis of crocin, picrocrocina and safranal by saffron stigma-like structures proliferated in vitro. Agric Biol Chem  1987; 9:2395–2400.
  21.  Schmidt M, Betti G, Hensel A.Saffron in phytotherapy: Pharmacology and clinical uses. Wien Med Wochenschr 2007; 157/13–14: 315–319.
  22.  Anastasaki E, Kanakis C, Pappas C, Maggi L, del Campo CP, Carmona M. Geographical differentiation of saffron by GC–MS/FID and chemometrics. Eur Food Res Technol  2009; 229:899–905.
  23.  Maggi L, Carmona M, del Campo CP, Kanakis CD, Anastasaki E, Tarantilis PA. Worldwide market screening of saffron volatile composition. J Sci Food Agric  2009; 89:1950–1954.
  24.  Formisano C, Mignola E, Senatore F, Bancheva S, Bruno M, Rosselli S. Volatile constituents of aerial parts of Centaurea sibthorpii (Sect. Carduiformes, Asteraceae) from Greece and their biological activity. Nat Prod Res 2008; 22:840–845.
  25.  Formisano C, Rigano D, Senatore F, Celik S, Bruno M, Rosselli S. Volatile constituents of aerial parts of three endemic Centaurea species from Turkey: Centaurea amanicola Hub.-Mor., Centaurea consanguinea DC. and Centaurea ptosimopappa Hayek and their antibacterial activities. Nat Prod Res 2008; 22:833–839.
  26.  Radulović N, Dekić M, Stojanović-Radić Z, Palić R. Volatile constituents of Erodium cicutarium (L.) L’ Hérit. (Geraniaceae). Cent Eur J Biol 2009; 4:404–410.
  27.  Zhu M, Li E, He H. Determination of volatile chemical constitutes in tea by simultaneous distillation extraction, vacuum hydrodistillation and thermal desorption. Chromatographia 2008; 68:603–610.
  28.  Jia-jia L, Dong-liang Y, Yan Z, Yao Y, Fu-xiang C, Jian-ming Z, et al. Chemical component and antimicrobial activity of volatile oil of Calycopteris floribunda. J Cent South Univ Technol 2009; 16:0931−0935.
  29.  Demeter Z, Sura´nyi G, Molnaor VA, Sramko G, Beyer D, Ko´nya Z, et al. Somatic embryogenesis and regeneration from shoot primordia of Crocus heuffelianus. Plant Cell Tiss Organ Cult 2010; 100:349–353.
  30.  Kaack K, Christensen LP, Hughes M, Eder R. Relationship between sensory quality and volatile compounds of elderflower (Sambucus nigra L.) extracts. Eur Food Res Technol 2006; 223:57–70.
  31.  Pereiraa J, Câmara JS. Effectiveness of different solid-phase microextraction fibres for differentiation of selected Madeira island fruits based on their volatile metabolite profile-Identification of novel compounds. Talanta 2011; 83:899–906.
  32.  Lazarevic´J, Radulovic N, Zlatkovic B, Palic R. Composition of Achillea distans Willd. subsp. distans root essential oil. Nat Prod Res 2010; 24:718–731.
  33.  ISO/TS 3632-1, 2 Saffron (Crocus sativus L.) Part 1: Specifications, Part 2: Test Methods; Geneva, Switzerland: ISO.2003.
  34.  Hadizadeh F, Mahdavi M, Emami SA, Khashayarmanesh Z, Hassanzadeh M, Asili J. Evaluation of ISO method in saffron qualification. Acta Horticulturae  2007; 739:405–410.
  35.  Tarantilis PA, Polissiou M,  Manfait M. Separation of picrocrocin, cistrans- crocins and safranal of saffron using high-performance liquid chromatography with photodiode-array detection. J Chromatogr A 1994; 664:55–61.
  36.  Lozano P, Delgado D, Gomez D, Rubio M, Iborra JL. A non-destructive method to determine the safranal content of saffron (Crocus sativus L.) by supercritical carbon dioxide extraction combined with high-performance liquid chromatography and gas chromatography. J Biochem Biophs Methods 2000; 43:367–378.
  37.  Kanakis CD, Daferera DJ, Tarantilis PA,  Polissiou MG. Qualitative determination of volatile compounds and quantitative evaluation of safranal and 4-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde (HTCC) in Greek saffron. J Agric Food Chem  2004; 52:4515–4521.
  38.  Sujata V, Ravishankar GA, Venkataraman LV.Methods for the analysis of the saffron metabolites crocin, crocetins, picrocrocin and safranal for the determination of the quality of the spice using thin-layer chromatography, high-performance liquid chromatography and gas chromatography. J Chromatogr A 1992; 624:497–502.
  39.  Alissandrakis E, Tarantilis PA, Harizanis P, Polissiou M. Comparison of the volatile composition in thyme honeys from several origins in Greece. J Agric Food Chem 2007; 55:8152–8157.
  40.  Del Toro-Sánchez L, Sánchez S, Ortiz MA, Villanueva S, Lugo-Cervantes E. Generation of aroma compounds from Ditaxis heterantha by Saccharomyces cerevisiae. Appl Microbiol Biotechnol  2006; 72:155–162.
  41.  Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res 2005; 19:997−1000.
  42.  Kianbakht S, Mozaffari K. Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats. J Med Plan  2009; 5:30-38.
  43.  Pathan SA, Zaidi SMA, Jain GK, Vohora D, Ahmad FJ, Khar RK. Anticonvulsant evaluation of safranal in pentylenetetrazole-induced status epilepticus in mice. Int J Essential Oil Therapeutics??  2009; 3:106-108
  44.  Ghoshooni H, Daryaafzoon M, Sadeghi-Gharjehdagi S, Zardooz H, Sahraei H, Tehrani SP, et al. Saffron (Crocus sativus) ethanolic extract and its constituent, safranal, inhibits morphine-induced place preference in mice. Pak J Biol Sci  2011; 14:939-944.
  45.  Escribano J, Alonso GL, Coca-Prados M, Fernandez, JA. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett 1996; 100:23−30.
  46.  Liu Z, Xu XH, Liu TY, Hong ZY, Urade Y, Huang ZL, et al. Safranal enhances non-rapid eye movement sleep in pentobarbital-treated mice. CNS Neurosci Ther  2012; 18:623-630.
  47.  Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res  2009; 23:768-74.
  48.  Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia  2005; 76:722–724.
  49.  Sadeghnia HR, Cortez MA, Liu D,Hosseinzadeh H, Snead OC. Antiabsence effects of safranal in acute experimental seizure models: EEG and autoradiography. J Pharm Pharmaceut Sci  2008; 11:1-14.
  50.  Atanassova-Shopova S, Roussinov KS, Boycheva I. On certain central neurotropic effects of lavender essential oil. II. Studies on the effects of linalool and of terpinenol. Izv Inst Fiziol  1973; 15:149–156.
  51.  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.
  52.  Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci2005; 8:394–399.
  53.  Hosseinzadeh H, Ziaei T. Effects of Crocus sativus stigma extract and its constituents, crocin and safranal, on intact memory and scopolamine induced learning deficits in rats performing the Morris water maze task. J Med Plants  2006; 5:40–50.
  54.  Hosseinzadeh H, Sadeghnia HR, Rahimi A.Effect of safranal on extracellular hippocampal levels of glutamate and aspartate during kainic Acid treatment in anesthetized rats. Planta Med  2008; 74:1441-1445.
  55.  Golmohammadzadeh Sh, Imani F, Hosseinzadeh H, Jaafari MR. Preparation, characterization and evaluation of sun protective and moisturizing effects of nanoliposomes containing safranal .Iran J Basic Med Sci  2011; 14:521-533.
  56.  Shamsa A, Hosseinzadeh H, Molaei M, Shakeri MT, Rajabi O. Evaluation of Crocus sativus L. (saffron)on male erectile dysfunction : A pilot study. Phytomedicine  2009; 16;690–693.
  57.  Nemati H, Boskabady MH, Ahmadzadef Vostakolaei H. Stimulatory effect of Crocus sativus (saffron) on b2-adrenoceptors of guineapigtrachealchains Phytomedicine  2008; 15:1038–1045.
  58.  Boskabady MH, Ghasemzadeh Rahbardar M, Jafari Z. The effect of safranal on histamine (H1) receptors of guinea pig tracheal chains. Fitoterapia 2011; 82:162–167.
  59.  Hosseinzadeh H, Tabeshpur J, Mehri S. Effect of Saffron extract on Acrylamide- induced toxicity:  In vitro and in vivo assessment. Chin J Integr Med 2012. In Press.
  60.  Mehri S, Abnous K, Mousavi SH, Shariaty VM, Hosseinzadeh H. Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells. Cell Mol Neurobiol 2012; 32:227-235.
  61.  Hariri AT, Moallem SA, Mahmoudi M, Hosseinzadeh H. The effect of crocin and safranal, constituents of saffron, against subacute effect of diazinon on hematological and genotoxicity indices in rats. Phytomedicine 2010; 18:499–504.
  62.  Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H. Subacute effects of diazinon on biochemical indices and specific biomarkers in rats: protective effects of crocin and safranal. Food Chem Toxicol  2011; 48: 2803–2808.
  63.  Boroushaki MT, Sadeghnia HR. Protective effect of safranal against gentamicin-induced nephrotoxicity in rat. Iran J Med Sci 2009; 34:285-288.
  64.  Boroushaki MT, Mofidpour H, Sadeghnia HR. Protective effect of safranal against hexachlorobutadiene-induced nephrotoxicity in rat. Iran J Med Sci 2007; 32:173-176.
  65.  Kianbakht S, Hajiaghaee R. Anti-hyperglycemic effects of saffron and its active constituents, crocin and safranal, in alloxan-induced diabetic rats. J Med Plants  2011; 10:82-89.
  66.  Boskabady MH, Aslani MR. Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its possible mechanisms. J Pharm Pharmacol 2006; 58:1385-1390.
  67.  Nugent M, Artru AA, Michenfclder JD. Cerebral metabolic vascular and protective effects of midazolam maleate: Comparison to diazepam. Anesthesiology 1982; 56:172–176.
  68.  Fatehi Hassanabad Z, Fatehi M, Imen Shahidi, M. Endothelial dysfunction in aortic rings and mesenteric beds isolated from deoxycorticosterone acetate hypertensive rats: possible involvement of protein kinase C. Eur J Pharmacol 2004; 494:199-204.
  69.  Bharti S, Golechha M, Kumari S, Siddiqui KM, Arya DS. Akt/GSK-3b/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia–reperfusion injury in rats. Eur J Nutr 2011; DOI 10. 1007/s00394-011-0251-y.
  70.  Sadeghnia HR, Boroushaki MT, Mofidpour H. Effect of safranal, a constituent of saffron (Crocus sativus l.), on lipid peroxidation level during renal ischemia-reperfusion injury in rats. Iran J Basic Med Sci Fall 2005; 8:179-185.
  71.  Hosseinzadeh H, Modaghegh MH, Saffari Z. Crocus sativus L. (Saffron) extract and its active constituents (crocin and safranal) on ischemiareperfusion in rat skeletal muscle. Evid Based Complement Alternat Med 2009; 6:343–350.
  72.  Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of C. sativus L. stigma and petal extracts in mice. BMC Pharmacol 2002; 15:2-7.
  73.  Nasri S, Hosseini SY, Sahraei H, Zardouz H. Inhibition of pain and inflamation induced by formalin in male mice by ethanolic extract of saffron (crocus sativus) and its constituents; crocin and safranal. Kowsar Med J 2011; 15:189-195.
  74.  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; 83:888-895.
  75.  Hosseinzadeh H, Shariaty V. Anti-nociceptive effect of safranal, a constituent of Crocus sativus (saffron), in mice. Pharmacologyonline 2007; 2:498–503.
  76.  Pintado C, Miguel A, Acevedo O, Nozal         L, Novella JL, Rotger R. Bactericidal effect of saffron (Crocus sativus L.) on Salmonella enterica during storage. Food Control 2011; 22:638-642.
  77.  Kanakis CD, Tarantilis PA, Tajmir-Riahi HA, Polissiou1dna MG. Interaction with saffron’s secondary metabolites safranal, crocetin, and dimethylcrocetin. DNA Cell Biol 2007; 26:63–70.
  78.  Hoshyar R, Bathaie SZ, Ashrafi M. Interaction of safranal and picrocrocin with ctDNA and their preferential mechanisms of binding to GC- and AT-Rich oligonucleotides. DNA Cell Biol 2008; 27:665–673.
  79.  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; 27:657-64.
  80.  Hosseinzadeh H, Sadeghnia HR. Effect of safranal, a constituent of Crocus sativus (Saffron), on methyl methanesulfonate (MMS)–induced DNA damage in mouse organs: an alkaline single-cell gel electrophoresis (Comet) assay. DNA Cell Biol  2007; 26:841–846.
  81.  Hosseinzadeh H, Shakib SS, Khadem Sameni A, Taghiabadi E. Clin Biochem  2011; 44:S122.
  82.  Kanakis CD, Tarantilis PA, Tajmir-Riahi HA, Polissiou MG. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J Agric Food Chem 2007; 7; 55:970-977.
  83.  Behravan J, Hosseinzadeh H, Rastgoo A, Malekshah OM, Hessani M. Evaluation of the cytotoxic activity of crocin and safranal using potato disc and brine shrimp assays. Physiol Pharmacol 2010; 13:397 – 403.
  84.  Abdullaev FI, Riveron-Negrete L, Caballero-Ortegaa H, Manuel Hernandez J, Perez-Lopez I, Pereda-Miranda R, et al. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol      in Vitro 2003; 17:731–736.
Iranian Journal of Basic Medical Sciences
Volume 16, Issue 1 - Serial Number 1
SAFFRON SPECIAL ISSUE
January 2013
Pages 12-26

Files

Share

How to cite

Statistics