Aqueous Extract of Saffron (Crocus sativus) Increases Brain Dopamine and Glutamate Concentrations in Rats

Hosseinali Ettehadi, Seyedeh Nargesolsadat Mojabi, Mina Ranjbaran, Jamal Shams, Hedayat Sahraei, Mahdi Hedayati, Farzad Asefi

Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Psychiatry, Faculty of Medicine, and Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Fat Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Institute of Science and Technology, Tehran, Iran.
Neuroscience Research Center, Baqyiatallah (a.s.) University of Medical Sciences, Tehran, Iran.

DOI: 10.4236/jbbs.2013.33031                

Abstract

Recent studies involving human and animal models have identified that saffron helps in the improvement of depression. Antidepressants are known to function in part by increasing brain serotonin, norepinephrine and dopamine concentrations. Therefore, to identify the cellular and molecular mechanism(s) underlying this property of saffron, we measured changes in rat brain dopamine, serotonin, norepinephrine and glutamate concentrations after administration of varying doses of an aqueous extract of saffron stigma. Male Wistar rats (250 ± 30 g) were administered a single dose of saffron extract (5, 25, 50, 100, 150, and 250 mg/kg, i.p.), fluoxetine (10 mg/kg, i.p.), and/or desipramine (50 mg/kg, i.p.) and were sacrificed 30 min later. Brains were removed, homogenized, and centrifuged at 4?C. The supernatant was used for subsequent neurotransmitter detection by ELISA. Our results indicated that the aqueous extract of saffron (50, 100, 150 and 250 mg/kg, i.p.) increased brain dopamine concentration in a dose-dependent manner compared with saline. In addition, the brain glutamate concentration increased in response to the highest dose of the extract (250 mg/kg, i.p.). Interestingly, the extract had no effect on brain serotonin or norepinephrine concentration. Our findings show that the aqueous extract of saffron contains an active component that can trigger production of important neurotransmitters in brain, namely, dopamine and glutamate. In addition, these results provide a cellular basis for reports concerning the antidepressant properties of saffron extract in humans and animals.

Keywords

Saffron; Glutamate; Dopamine; Norepinepherine; Serotonin

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. J. Mann, “The Medical Management of Depression,” The New England Journal of Medicine, Vol. 353, No. 17, 2005, pp. 1819-1834. doi:10.1056/NEJMra050730
[2]	T. M. MacDonald, “Treatment of Depression: Prescription for Success?” Primary Care Psychiatry, Vol. 3, Suppl. 1, 1997, pp. 7-10.
[3]	J. Sarris, “Herbal Medicines in the Treatment of Psychiatric Disorders: A Systematic Review,” Phytotherapy Research, Vol. 21, No. 8, 2007, pp. 703-716. doi:10.1002/ptr.2187
[4]	M. Imenshahidi, H. Zafaria and H. Hosseinzadeh, “Effects of Crocin on the Acquisition and Reinstatement of Morphine-Induced Conditioned Place Preference in Mice,” Pharmacologyonline, Vol. 1, No. 1, 2011, pp. 10071013.
[5]	B. Khakpour, M. Rostampour-Vajargah, H. Sahraei, M. Kamalinejad and J. Shams, “Effects of the Crocus sativus L. Extract on the Acquisition and Expression of Morphine-Induced Behavioral Sensitization in Male Mice,” Kowsar Medical Journal, Vol. 12, No. 4, 2007, pp. 305313.
[6]	M. Mobasher, H. Sahraei, B. Sadeghi-Rad, M. Kamalinejad and J. Shams, “ The Effects of the Crocus sativus Extract on the Acquisition and Expression of Morphine-Induced Conditioned Place Preference in Mice,” Journal of Rafsanjan University of Medical Sciences, Vol. 5, No. 3, 2005, pp. 143-150.
[7]	N. Mojabi, A. Eidi, M. Kamalinejad, F. Khamseh, A. Khoshbaten, A. Noroozzadeh, F. Zighymat and H. Sahraei, “Study of the Effects of Alcoholic Extract of Crocus sativus on the Acquisition and Expression of Morphine-Induced Conditioned Place Preference in Rats,” Kowsar Medical Journal, Vol. 13, No. 3, 2008a, pp. 197-210.
[8]	N. Mojabi, A. Eidi, M. Kamalinejad, F. Khamseh, A. Khoshbaten, A. Noroozzadeh, F. Zighymat and H. Sahraei, “Study of the Effects of Intra-Nucleus Accumbens Shell Injections of Alcohlic Extract of Crocus sativus on the Acquisition and Expression of Morphine-Induced Conditioned Place Preference in Rats,” Physiology and Pharmacology, Vol. 12, No. 2, 2008b, pp. 121-128.
[9]	H. Sahraei, J. Shams, S. Marjani, S. Molavi and M. Mohammadi, “Effects of the Crocus sativus L. Extract on the Acquisition and Expression of Morphine-Induced Behavioral Sensitization in Female Mice,” Journal of Medicine Plants, Vol. 6, No. 21, 2007, pp. 26-35.
[10]	H. Sahraei, M. Mohammadi, M. Kamalinejad, J. Shams, H. Ghoshooni and A. Noroozzadeh, “Effects of the Crocus sativus Extract on the Acquisition and Expression of Morphine-Induced Conditioned Place Preference in Female Mice,” Journal of Medicine Plants, Vol. 25, No. 1, 2005, pp. 40-49.
[11]	H. Hosseinzadeh, and Z. Jahanian, “Effect of Crocus sativus L. (Saffron) Stigma and Its Constituents, Crocin and Safranal, on Morphine Withdrawal Syndrome in Mice,” Phytotherapy Research, Vol. 24, No. 5, 2010, pp. 726-30.
[12]	M. Schmidt, G Betti and A. Hensel, “Saffron in Phytotherapy: Pharmacology and Clinical Uses,” Wiener Medizinische Wochenschrift, Vol. 157, No. 13-14, 2007, pp. 315-319. doi:10.1007/s10354-007-0428-4
[13]	H. Zardooz, F. Rostamkhani, J. Zaringhalam and F. Faraji Shahrivar, “Plasma Corticosterone, Insulin and Glucose Changes Induced by Brief Exposure to Isoflurane, Diethyl Ether and CO2 in Male Rats,” Physiolical Research, Vol. 59, No. 6, 2010, pp. 973-938.
[14]	H. Hosseinzadeh and M. Nassiri-Asl, “Avicenna’s (Ibn Sina) the Canon of Medicine and Saffron (Crocus sativus): A review,” Phytotherapy Research, Vol. 27, No. 4, 2013, pp. 475-483. doi:10.1002/ptr.4784
[15]	S. H. Akhondzadeh, H. Fallah-Pour, K. Afkham, A. H. Jamshidi and F. Khalighi-Cigaroudi, “Comparison of Crocus sativus L. and Imiperamine in the Treatment of Mild to Moderate Depression: A Pilot Double-Blind Randomized Trial,” BMC Complementary and Alternative Medicine, Vol. 4, No. 1, 2004, pp. 12-16.
[16]	A. A. Noorbala, S. H. Akhondzadeh, N. Tahmacebi-Pour and A. H. Jamshidi, “Hydro-Alcoholic Extract of Crocus sativus L. Versus Fluoxetine in the Treatment of Mild to Moderate Depression: A Double-Blind, Randomized Pilot Trial,” Journal of Ethnopharmacology, Vol. 97, No. 2, 2005, 281-284. doi:10.1016/j.jep.2004.11.004
[17]	E. Moshiri, A. Noorbala, A. Jamshidi, S. H. Abbasi and S. H. Akhondzadeh, “Comparison of Petal of Crocus sativus L. and Fluoxetine in the Treatment of Depressed Outpatients: A Pilot Double-Blind Randomized Trial,” Progress in Neuropsychopharmacology and Biological Psychiatry, Vol. 1, No. 2, 2007, pp. 439-442.
[18]	G. Karimi, H. Hosseinzadeh and P. Khaleghpanah, “Study of Antidepressant Effect of Aqueous and Ethanolic of Crocus sativus in Mice,” Iranian Journal of Basic Medical Sciences, Vol. 4, No. 3, 2001, pp. 11-15.
[19]	S. Akhondzadeh, M. Shafiee-Sabet, M. H. Harirchian, M. Togha, H. Cheraghmakani, S. Razeghi, S. S. Hejazi, M. H. Yousefi, R. Alimardani, A. Jamshidi, F. Zare and A. Moradi, “Saffron in the Treatment of Patients with Mild to Moderate Alzheimer’s Disease: A 16-Week, Randomized and Placebo-Controlled Trial,” Journal of Clinical Pharmacy and Therapeutics, Vol. 35, No. 5, 2010, pp. 581588. doi:10.1111/j.1365-2710.2009.01133.x
[20]	P. Dharmshaktu,V. Tayal and B. S. Kalra, “Efficacy of Antidepressants as Analgesics: A Review,” The Journal of Clinical Pharmacology, Vol. 52, No. 1, 2012, pp. 6-17. doi:10.1177/0091270010394852
[21]	M. Lechtenberg, D. Schepmann, M. Niehues, N. Hellenbrand, B. Wunsch and A. Hensel, “Quality and Functionality of Saffron: Quality Control, Species Assortment and Affinity of Extract and Isolated Saffron Compounds to NMDA and U1 (Sigma-1) Receptors,” Planta Medica, Vol. 74, No. 7, 2008, pp. 764-772.
[22]	J. Cami and M. Farre, “Drug Addiction,” The New England Journal of Medicine, Vol. 349, No. 10, 2003, pp. 975-986. doi:10.1056/NEJMra023160