Safranal as a safe compound to mice immune system

Document Type: Original Research Article


1 Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

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

3 Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objectives: The aim of the present study was to investigate immunotoxic effect of safranal (SAF), a main component of Crocus sativus essential oil, using Balb/c mice.
Materials and Methods: SAF was administered intraperitoneally at doses of 0.1, 0.5 and 1 ml/kg for 3 weeks. Hystopathological examination of spleen and bone marrow, cellularity of spleen, delayed type of hypersensitivity (DTH) response, hemagglutination titer (HA), cytokine production and lymphocyte proliferation assay were studied in various groups of animals.
Results: Spleen cellularity for SAF groups (0.1 ml/kg SAF: 6.68 [± 0.88] × 107, 0.5 ml/kg SAF: 8.16 [± 1.33] × 107, 1 ml/kg SAF: 6.12 [± 0.59] × 107) did not significantly differ as compared to vehicle control (8.52 [± 1.36] × 107; p > 0.05). In addition, SAF at all doses could not produce any significant changes in hematological parameters, HA titer, DTH and lymphoproliferation responses, as well as in release of cytokines by isolated splenocytes (p > 0.05). Despite a few studies demonstrating some immunomodulatory effects for saffron extract, SAF as a major constituent of saffron did not induce any marked effects in immune system parameters of mice.
Conclusion: Contrary to the toxicological studies which have indicated that SAF is more toxic than other active constituents in saffron stigma, at least it was found to be safe to mice immune system and has no toxicity on humoral and cellular immune responses.


Main Subjects

Abdullaev FI, Riveron NL, Caballero-Ortegaa H, Manuel Hernandez J, Perez-Lopez I, Pereda-Miranda R, Espinosa-Aguirre JJ. 2003. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol Invitro, 17: 731–736.

Assimopoulou AN, Sinakosa Z, Papageorgiou VP. 2005. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res, 19: 997-1000.

Bendich, A. 1993. Physiological role of antioxidants in the immune system. J Dairy Sci, 76: 2789-2794.

Boskabady MH, Aslani MR. 2006. Relaxant effect of Crocus sativus(saffron) on guinea-pig tracheal chains and its possible mechanisms. J Pharm Pharmacol, 58: 1385-1390.

Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A. 2011. The effect of Crocus sativus extract on human lymphocytes' cytokines and T helper 2/T helper 1 balance. J Med Food, 14: 1538-1545.

Boskabady MH, Byrami G, Feizpour A. 2014. The effect of safranal, a constituent of Crocus sativus (saffron), on tracheal responsiveness, serum levels of cytokines, total NO and nitrite in sensitized guinea pigs. Pharmacol Rep, 66: 56-61.

De La Fuente M, Victor VM. 2000. Anti-oxidants as modulators of immune function. Immunol Cell Biol, 78: 49-54.

Escribano J, Alonso G, Coca-Prados M, Fernandez JA. 1996. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett, 100: 23-30.

Fararjeh M, Mohammad MK, Bustanji Y, Alkhatib H, Abdalla S. 2008. Evaluation of immunosuppression induced by metronidazole in Balb/c mice and human peripheral blood lymphocytes. Int Immunopharmacol, 8: 341-350.

Farsam V, Hassan ZM, Zavaran-Hosseini A, Noori S, Mahdavi M, Ranjbar M. 2011. Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo. Int Immunopharmacol, 11: 1802-1808.

Hasani-Ranjbar S, Larijani B, Abdollahi M. 2009. A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Inflamm Allergy Drug Targets, 8: 2-10.

Hosseinzadeh H, Ghenaati J. 2006. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia, 77: 446–448.

Hosseinzadeh H, Karimi G, Niapoor M. 2004. Antidepressant effects of Crocus sativus stigma extracts and its constituents, crocin and safranal, in mice. Acta Hortic, 650: 435–445.

Hosseinzadeh H, Shariaty VM. 2007. Anti-nociceptive effect of safranal, a constituent of Crocus sativus (saffron), in mice. Pharmacologyonline, 2: 498-503.

Hosseinzadeh H, Talebzadeh F. 2005. Anticonvulsant evaluation of safranal and crocin from Crocus sativusin mice. Fitoterapia, 76: 722–724.

Kanakis CD, Tarantilis PA, Tajmir-Riahi HA, Polissiou MG. 2007. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J Agric Food Chem, 55: 970-977.

Kianbakht S, Mozaffari K. 2009. 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,  5: 30-38.

Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65: 55-63.

Neishabouri EZ, Hassan ZM, Azizi E, Ostad SN. 2004. Evaluation of immunotoxicity induced by diazinon in C57bl/6 mice. Toxicology, 196: 173–179.

Noori S, Taghikhani M, Hassan ZM, Allameha A, Mostafaei A. 2010. Tehranolide molecule modulates the immune response, reduce regulatory T cell and inhibits tumor growth in vivo. Mol Immunol, 47: 1579-1584.

Pintado C, de Miguel A, Acevedo O, Nozal L, Novella Jl, Rotger R. 2011. Bactericidal effect of saffron (Crocus sativusL.) on Salmonella enterica during storage. Food Control, 22: 638-642.

Rahnama M, Mahmoudi M, Zamani Taghizadeh Rabe S, Balali-Mood M, Karimi G, Tabasi N, Riahi-Zanjani B. 2014. Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model. J Immunotoxicol, 1-8.

Rezaee R, Hosseinzadeh H. 2013. Safranal: From an Aromatic Natural Product to a Rewarding Pharmacological Agent. Iran J Basic Med Sci, 16: 12-26.

Riahi B, Rafatpanah H, Mahmoudi M, Memar B, Brook A, Tabasi N, Karimi G. 2010. Immunotoxicity of paraquat after subacute exposure to mice. Food Chem Toxicol, 48: 1627-1631.

Vaibhav D, Arunkumar W, Abhijit MP, Arvind S. 2011. Antioxidants as immunomodulator: An expanding research. Avenue Int J Curr Pharmaceut Res, 3: 8-10.

Vijayabhargava K, Asad M. 2011. Effect of Stigmas of Crocus sativus L.(saffron) on Cell Mediated and Humoral Immunity. The Nat Prod J, 1: 151-155.

Zargari A. 1990. Medicinal Plants. Tehran University Press, 574-578.

Zheng KC, Ariizumi M, Todoriki H, Shinjo M. 1998. Cytokine production bysplenocytes and thymocytes in mice after intranasal exposure to toluenediisocyanate. J Occup Health, 40: 279–284.

Ziaee T, Razavi BM, Hosseinzadeh H. 2014. Saffron Reduced Toxic Effects of its Constituent, Safranal, in Acute and Subacute Toxicities in Rats. Jundishapur J Nat Pharm Prod, 9: 3-8.