ArticlePDF Available

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

Authors:

Abstract and Figures

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.
Content may be subject to copyright.
Journal of Behavioral and Brain Science, 2013, 3, 315-319
doi:10.4236/jbbs.2013.33031 Published Online July 2013 (http://www.scirp.org/journal/jbbs)
Aqueous Extract of Saffron (Crocus sativus) Increases
Brain Dopamine and Glutamate Concentrations in Rats
Hosseinali Ettehadi1, Seyedeh Nargesolsadat Mojabi2, Mina Ranjbaran2,
Jamal Shams3, Hedayat Sahraei2*, Mahdi Hedayati4, Farzad Asefi5
1Institute of Science and Technology, Tehran, Iran
2Neuroscience Research Center, Baqyiatallah (a.s.) University of Medical Sciences, Tehran, Iran
3Department of Psychiatry, Faculty of Medicine, and Neuroscience Research Center,
Shahid Beheshti University of Medical Sciences, Tehran, Iran
4Fat Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Email: *h.sahraei@bmsu.ac.ir
Received December 10, 2012; revised March 2, 2013; accepted March 20, 2013
Copyright © 2013 Hosseinali Ettehadi et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 concentra-
tions. 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 ad-
dition, the brain glutamate concentration increased in response to the highest dose of the extract (250 mg/kg, i.p.). In-
terestingly, 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
1. Introduction
Depression is a common and pernicious illness that can
occur at many stages of life. Between 15% and 20% of
patients have symptoms that persist for at least 2 years,
and often these patients do not fully recover between de-
pressive episodes [1]. Depression is also associated with
high rates of relapse, recurrence, disability, and death [2].
Collectively, the high rates of chronicity, relapse, recur-
rence, morbidity and mortality highlight the importance
of safe and effective long-term pharmacological treat-
ment of this disease. However, evidence indicates that in-
dividuals with depression are seriously undertreated and
receive inappropriate or inadequate treatment, with enor-
mous costs to individuals and society [1].
Saffron, Crocus sativus L. (Iridaceae), is used in folk
medicine as an aphrodisiac and antispasmodic agent,
expectorant and antidepressant [3]. Recent studies have
demonstrated that saffron extract and its constituent, cro-
cin, show interactions with morphine reward properties
[4-10]. Interestingly, these studies have shown that the
extract may interact with the neural elements located in
the shell region of the nucleus accumbens [8]. On the
other hand, Hosseinzadeh and Jahanian have shown that
the extract and safranal and crocin can reduce the signs
of morphine withdrawal syndrome in mice [11]. Che-
mical studies on Crocus sativus have shown the presence
of constituents such as crocin, crocetin, safranal, and
picrocrocin [12]. However, until today, there have been
*Corresponding author.
Copyright © 2013 SciRes. JBBS
H. ETTEHADI ET AL.
316
no studies on the effect of Crocus sativus extract on brain
neurotransmitter concentrations. In the present study, the
effect of saffron extract on brain serotonin, dopamine,
norepinephrine and glutamate concentrations in male rats
was investigated.
2. Materias and Methods
2.1. Experimental Animals
Male Wistar rats (250 - 300 g, Pasture Institute, Tehran,
Iran) were used throughout the study (8 rats for each ex-
periment). Animals were housed in groups of 4/cage in a
12/12 h light-cycle (lights on at 07.00 a.m.), with ad-lib
food and water available. The animals were randomly
allocated to different groups of the experiment. All ex-
periments were conducted in accordance with standard
ethical guidelines and approved by the local ethical
committee (The Baqiyatallah (a.s.) University of Medical
Committee on the Use and Care of Animals, 81/021, July
10, 2002).
2.2. Drugs
Fluoxetine hydrochloride [N-methyl-3-[(4-trifluoromethyl)
phenoxy]-3-phenylpropylamine hydrochloride] and de-
sipramine hydrochloride [10-11-dihydro-N-methyl-5H-di-
benz (Z) [b,f] azepine-5-propanamine hydrochloride]
(TOCRIS Bioscience, UK) were dissolved in sterile sa-
line and administered intraperitoneally at a concentration
of 1 ml/kg; the extract was prepared immediately before
use. The control groups were administered saline.
2.3. Plant Material
The saffron used in this study was a gift from Ta-
lakaran-E-Mazraeh Agricultural Co. (Torbat Heydarieh,
Khorasan-e-Razavi, Iran). The plant was authenticated
by M. Kamalinejad (Department of Pharmacognosy, Fa-
culty of Pharmacy, Shahid Beheshti University of Medi-
cal Sciences, Tehran, Iran) and a voucher specimen
coded P-408 has been deposited at the herbarium of the
Department of Pharmacognosy, Faculty of Pharmacy,
Shahid Beheshti University of Medical Sciences, Tehran,
Iran. Crocus sativus stigma is typically used as an addi-
tive and in herbal medicine. To prepare the extract, 100 g
of dried and milled stigma was extracted with 1000 ml
distilled water by maceration. The extract was dried at
35˚C - 40˚C, and the yield of extraction was 23 mg of
freeze-dried powder per 100 mg dry stigma. The extract
was dissolved in normal saline and immediately admin-
istered to the animals.
2.4. Brain Preparation
Thirty minutes after drug and/or extract injection, ani-
mals were killed in a CO2 box [13], beheaded by a guil-
lotine, and their brains were removed by a specialist in
less than a minute. Brains were homogenized in a Falcon
tube containing 10 ml of cool (0˚C) sterile saline and
centrifuged at 3000 rpm/min for 5 min at 4˚C. The su-
pernatant was used for subsequent neurotransmitter de-
tection by ELISA. On the basis of our previous studies,
an interval time of 30 min was selected; this time was
considered to be sufficient for extract action.
2.5. Statistical Analysis
Data are represent as means ± standard error of mean
(SEM) of the neurotransmitters concentration. One way
analysis of variance (One-Way ANOVA) following by
Tukey post hoc was used for statistical analysis. P < 0.05
differences were considered significant.
3. Results
3.1. Effects of Saffron Water Extract on Brain
Serotonin Concentration
The effect of different doses of saffron extract (5, 25, 50,
100, 150 and 200 mg/kg, i.p.) on brain serotonin is
shown in Figure 1. The animals received either saline (1
ml/kg, i.p.), or fluoxetine (10 mg/kg, i.p.), desipramine
(50 mg/kg, i.p.), saffron extract (5, 25, 50, 100, 150 and
200 mg/kg, i.p.) and 30 min later were sacrificed. One
way ANOVA indicated that fluoxetine can increase brain
serotonin significantly but neither desipramine nor saf-
fron extract can increase brain serotonin [F(8, 64) = 1.23,
P < 0.05], Figure 1.
3.2. Effects of Saffron Extract on Brain
Dopamine Level
Our results indicated that both fluoxetine (10 mg/kg, i.p.)
and desipramine (50 mg/kg, i.p.) can increase dopamine
Figure 1. Effects of different doses of the aqueous extract of
saffron on serotonin release in the brain. Each point is the
mean ± SEM of 8 rat brains. ***P < 0.001 different from
saline control group.
Copyright © 2013 SciRes. JBBS
H. ETTEHADI ET AL. 317
concentration on the animals. Interestingly, saffron ex-
tract can increase dopamine in a dose-dependent manner
(Figure 2). Further analysis indicated that the extract
dose of 250 mg/kg, i.p. was more potent in this regard
[F(8, 64) = 4.331, P < 0.001], Figure 2.
3.3. The Effect of Saffron Extract on Brain
Norepinephrine Concentration
The effect of saffron extract on brain norepinephrine
level is shown in Figure 3. Statistical analysis revealed
that none of the drugs can increase the brain norepineph-
rine level [F(8, 64) = 0.79, P > 0.05] (Figure 3), however,
the fluctuations were observed in the responses which
were not statistically significant.
3.4. The Effect of Saffron Extract on Brain
Glutamate Concentration
In the last part of the experiments, the effect of saffron
water extract on brain glutamate level was investigated.
Our results indicated that there were fluctuations in brain
glutamate level over doses of the extract. However, One
way ANOVA revealed that the extract can increase the
glutamate level in the dose of 250 mg/kg, i.p. [F(8, 64) =
2.108, P < 0.01], Figure 4.
4. Discussion
Our studies have shown that the aqueous extract of saf-
fron increases the release of important neurotransmitters,
such as dopamine and glutamate in rat brains. This study
also demonstrated that the effect of the extract on dopa-
mine release was dose dependent. Since there is no study
regarding the effect of saffron extract on neurotransmitter
release, our results could not be compared with other
investigations in this regard. However, it must be noted
that in this study, the effect of the extract on other im-
portant neurotransmitters such as gamma-amino butyric
acid (GABA) was not investigated. Moreover, it is not
clear which specific constituents of the extract (e.g.,
safranal, crocin, and others) are responsible for the ef-
fects observed in our experiments. Finally, it must be
noted that it was unclear whether dopamine or glutamate
was still present in the vesicles or whether it was released
into the synaptic space; this requires additional experi-
ments to determine.
While our data show that the extract has no effect on
serotonin and norepinephrine concentrations, it may be
speculated that if the interval time between extract injec-
tion and brain removal was increased, changes in these
neurotransmitter concentrations might be observed. This
problem can be resolved by the explanation that in other
experiments, the optimal time interval between extract
injection and initiation of the extract effect was approxi-
mately 30 min [5,9,10]. Several lines of evidence have
Figure 2. Effects of the aqueous extract of saffron on brain
dopamine concentration. Each point is the mean ± SEM of 8
rats. *P < 0.05, **P < 0.01, and ***P < 0.001 vs the control
group.
Figure 3. Effects of varying doses of the aqueous extract of
saffron on brain noradrenaline concentration. Each point is
the mean ± SEM of 8 rat brains.
Figure 4. Effects of the aqueous extract of saffron on brain
glutamate concentration. Each point is the mean ± SEM of
8 rats. *P < 0.05 and ***P < 0.001 vs the control group.
Copyright © 2013 SciRes. JBBS
H. ETTEHADI ET AL.
318
indicated that both the aqueous and organic extracts of
saffron can reduce depression in animals and humans [3,
13]. In this regard, it has shown that in comparison to
imipramine, the ethanolic extract of saffron (30 mg/day)
can reduce signs of depression in patients [14]. In addi-
tion, the efficacy of the organic extract of saffron in
mild-to-moderate depression improvement has been re-
ported in another study [15,16]. Moreover, both the or-
ganic and aqueous extracts of saffron can reduce signs of
depression induced by forced swimming stress in mice
[17].
With regard to other mental disorders, investigators
have shown that the organic extract of saffron can reduce
signs of Alzheimer’s disease during early phases of the
disease [18]. Previous studies have also shown that the
aqueous extract of saffron can induce rewarding proper-
ties, such as place preference and locomotor activity in
both male and female mice [9,10].
It is important to note that depression is defined by a
serious reduction in brain monoamine concentration [1],
and that antidepressant drugs increase monoamine con-
centration in the brain [1]. In this regard, investigators
have shown that an increase in brain dopamine concen-
tration, or administration of dopamine receptor agonists,
may improve depression in humans and rats [19]. Our
experiments have shown that brain dopamine concentra-
tion increases after treatment with saffron extract. Con-
sidering these two findings and other studies that saffron
extract can improve depression; our results can be con-
sidered as being in accordance with those of previous
studies. However, it is not clear which constituents of
saffron extract are responsible for the observed increase
in brain dopamine concentration. It must be noted that in
previous studies, crocin has been identified as the most
prominent constituent in the aqueous extract of saffron
[12], and it has been shown to inhibit N-methyl-D-as-
partate (NMDA) glutamate receptors and sigma opioid
receptors isolated from rat spinal cord [20]. Moreover, as
noted earlier, the extract can improve signs of Alzhei-
mer’s disease, probably because of its interaction with
NMDA receptors [18]. Considering these facts, one can
conclude that a constituent of the aqueous extract of saf-
fron, possibly crocin, interacts with NMDA receptors in
different parts of the brain to induce dopamine release.
This model is in agreement with the ability of the extract
to induce hyperactivity and place preference in mice [5,9,
10]. It is now clear that the dopamine concentration in
the reward area induced by abused drugs is the cause of
hyperactivity and place preference observed in animals
[21, 22]. Finally, the ability of the saffron extract to im-
prove memory, inhibit neuronal degeneration, and reduce
signs of depression may be because of the ability of the
extract to induce dopamine and/or glutamate release.
It is important to note that in our experiments we did
not measure regional changes in neurotransmitter levels
in the central nervous system. For example, we did not
focus on the change in dopamine concentration in brain-
specific regions or serotonin concentration in the raphe
nuclei. Thus, additional experiments are required to clar-
ify this issue.
In this study, we injected the extract intraperitoneally,
and it could be argued that different results might have
been obtained if the extract was injected intravenously.
In conclusion: It found that the aqueous extract of saf-
fron can induce dopamine and glutamate release in the
brain, which we suggest is related to the effect of the ex-
tract on depression rehabilitation observed in previous
studies.
5. Acknowledgements
This work was supported by the grants from Neurosci-
ence Research Center, Baqiyatallah (a.s.) University of
Medical Sciences and Neuroscience Research Center,
Shahid Beheshti University of Medical Sciences.
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: Prescrip-
tion for Success?” Primary Care Psychiatry, Vol. 3, Suppl.
1, 1997, pp. 7-10.
[3] J. Sarris, “Herbal Medicines in the Treatment of Psychiat-
ric Disorders: A Systematic Review,” Phytotherapy Re-
search, Vol. 21, No. 8, 2007, pp. 703-716.
doi:10.1002/ptr.2187
[4] M. Imenshahidi, H. Zafaria and H. Hosseinzadeh, “Ef-
fects of Crocin on the Acquisition and Reinstatement of
Morphine-Induced Conditioned Place Preference in Mi-
ce,” Pharmacologyonline, Vol. 1, No. 1, 2011, pp. 1007-
1013.
[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 Mor-
phine-Induced Behavioral Sensitization in Male Mice,”
Kowsar Medical Journal, Vol. 12, No. 4, 2007, pp. 305-
313.
[6] M. Mobasher, H. Sahraei, B. Sadeghi-Rad, M. Kamaline-
jad and J. Shams, “ The Effects of the Crocus sativus Ex-
tract on the Acquisition and Expression of Morphine-In-
duced 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. Sah-
raei, “Study of the Effects of Alcoholic Extract of Crocus
sativus on the Acquisition and Expression of Morphi-
ne-Induced Conditioned Place Preference in Rats,” Kow-
sar Medical Journal, Vol. 13, No. 3, 2008a, pp. 197-210.
Copyright © 2013 SciRes. JBBS
H. ETTEHADI ET AL.
Copyright © 2013 SciRes. JBBS
319
[8] N. Mojabi, A. Eidi, M. Kamalinejad, F. Khamseh, A.
Khoshbaten, A. Noroozzadeh, F. Zighymat and H. Sah-
raei, “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. Mo-
hammadi, “Effects of the Crocus sativus L. Extract on the
Acquisition and Expression of Morphine-Induced Be-
havioral Sensitization in Female Mice,” Journal of Medi-
cine 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 Cro-
cus sativus Extract on the Acquisition and Expression of
Morphine-Induced Conditioned Place Preference in Fe-
male 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 Phyto-
therapy: Pharmacology and Clinical Uses,” Wiener Medi-
zinische 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 sati-
vus): 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 Ran-
domized 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 Outpa-
tients: A Pilot Double-Blind Randomized Trial,” Pro-
gress in Neuropsychopharmacology and Biological Psy-
chiatry, Vol. 1, No. 2, 2007, pp. 439-442.
[18] G. Karimi, H. Hosseinzadeh and P. Khaleghpanah,
“Study of Antidepressant Effect of Aqueous and Ethano-
lic 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. Mo-
radi, “Saffron in the Treatment of Patients with Mild to
Moderate Alzheimer’s Disease: A 16-Week, Randomized
and Placebo-Controlled Trial,” Journal of Clinical Phar-
macy and Therapeutics, Vol. 35, No. 5, 2010, pp. 581-
588. 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. Hellen-
brand, B. Wunsch and A. Hensel, “Quality and Function-
ality 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 Eng-
land Journal of Medicine, Vol. 349, No. 10, 2003, pp.
975-986. doi:10.1056/NEJMra023160
... Anti-depressants are reported to function by triggering serotonin, norepinephrine, and dopamine levels in the brain. To confirm this, Ettehadi et al. [100] measured changes in rat brain dopamine, serotonin, norepinephrine, and glutamate concentrations; after the administration of an aqueous extract of saffron (50, 100, 150, and 250 mg/kg, i.p.), saffron increased brain dopamine concentration in a dose-dependent manner. In addition, the results showed that the aqueous extract of saffron, especially at the The role of the saffron extract is involved in inhibiting serotonin reuptake in synapses, thereby enhancing its positive effects while combating depression. ...
... Anti-depressants are reported to function by triggering serotonin, norepinephrine, and dopamine levels in the brain. To confirm this, Ettehadi et al. [100] measured changes in rat brain dopamine, serotonin, norepinephrine, and glutamate concentrations; after the administration of an aqueous extract of saffron (50, 100, 150, and 250 mg/kg, i.p.), saffron increased brain dopamine concentration in a dose-dependent manner. In addition, the results showed that the aqueous extract of saffron, especially at the dose of 250 mg/kg, increased the production of important neurotransmitters including dopamine and glutamate in rat brain [100]. ...
... To confirm this, Ettehadi et al. [100] measured changes in rat brain dopamine, serotonin, norepinephrine, and glutamate concentrations; after the administration of an aqueous extract of saffron (50, 100, 150, and 250 mg/kg, i.p.), saffron increased brain dopamine concentration in a dose-dependent manner. In addition, the results showed that the aqueous extract of saffron, especially at the dose of 250 mg/kg, increased the production of important neurotransmitters including dopamine and glutamate in rat brain [100]. In fact, it was reported based on animal studies that the possible anti-depressant activity of saffron bioactive compounds (crocin and safranal) could be mainly through inhibiting serotonin reuptake and the inhibition of dopamine and norepinephrine reuptake (Figure 3) [101]. ...
Article
Full-text available
Saffron is a valued herb, obtained from the stigmas of the C. sativus Linn (Iridaceae), with therapeutic effects. It has been described in pharmacopoeias to be variously acting, including as an anti-depressant, anti-carcinogen, and stimulant agent. The therapeutic effects of saffron are harbored in its bioactive molecules, notably crocins, the subject of this paper. Crocins have been demonstrated to act as a monoamine oxidase type A and B inhibitor. Furthermore, saffron petal extracts have experimentally been shown to impact contractile response in electrical field stimulation. Other research suggests that saffron also inhibits the reuptake of monoamines, exhibits N-methyl-D-aspartate antagonism, and improves brain-derived neurotrophic factor signaling. A host of experimental studies found saffron/crocin to be similarly effective as fluoxetine and imipramine in the treatment of depression disorders. Saffron and crocins propose a natural solution to combat depressive disorders. However, some hurdles, such as stability and delivery, need to be overcome.
... Similarly, Crocin has protective effects against PD via its anti-oxidative and anti-inflammatory properties [159]. In different animal models of neural damage, Crocin diminishes neural loss and ameliorates the symptoms of PD by increasing GSH [160][161][162], dopamine [160][161][162], and total thiols [161,162], and decreasing thiobarbituric acid reactive substance (TBARS) [160], NO [163], and AChE activity [161,162]. The anti-inflammatory and anti-oxidative roles of Crocin have been reported in other neurodegenerative disorders like ischemic brain injury [164][165][166][167], traumatic brain injury [168,169], spinal cord injury [170,171], and neuropathic pain [172], mostly through boosting anti-oxidants and reducing ROS. ...
... Similarly, Crocin has protective effects against PD via its anti-oxidative and anti-inflammatory properties [159]. In different animal models of neural damage, Crocin diminishes neural loss and ameliorates the symptoms of PD by increasing GSH [160][161][162], dopamine [160][161][162], and total thiols [161,162], and decreasing thiobarbituric acid reactive substance (TBARS) [160], NO [163], and AChE activity [161,162]. The anti-inflammatory and anti-oxidative roles of Crocin have been reported in other neurodegenerative disorders like ischemic brain injury [164][165][166][167], traumatic brain injury [168,169], spinal cord injury [170,171], and neuropathic pain [172], mostly through boosting anti-oxidants and reducing ROS. ...
... Similarly, Crocin has protective effects against PD via its anti-oxidative and anti-inflammatory properties [159]. In different animal models of neural damage, Crocin diminishes neural loss and ameliorates the symptoms of PD by increasing GSH [160][161][162], dopamine [160][161][162], and total thiols [161,162], and decreasing thiobarbituric acid reactive substance (TBARS) [160], NO [163], and AChE activity [161,162]. The anti-inflammatory and anti-oxidative roles of Crocin have been reported in other neurodegenerative disorders like ischemic brain injury [164][165][166][167], traumatic brain injury [168,169], spinal cord injury [170,171], and neuropathic pain [172], mostly through boosting anti-oxidants and reducing ROS. ...
Article
Full-text available
Crocin, an active ingredient derived from saffron, is one of the herbal components that has recently been considered by researchers. Crocin has been shown to have many anti-inflammatory and antioxidant properties, and therefore can be used to treat various diseases. It has been shown that Crocin has a positive effect on the prevention and treatment of cardiovascular disease, cancer, diabetes, and kidney disease. In addition, the role of this substance in COVID-19 pandemic has been identified. In this review article, we tried to have a compre- hensive review of the antioxidant and anti-inflammatory effects of Crocin in different diseases and different tissues. In conclusion, Crocin may be helpful in pathological conditions that are associated with inflammation and oxidative stress.
... EAE has been demonstrated to enhance the expression of the ER stress genes XBP-1/s [115]. Crocin administration on day 7 after EAE induction decreased the expression of ER stress genes XBP-1/s and repressed ER stress and inflammatory gene expression in the spinal cord [116]. ...
... Crocin antioxidant impact was equivalent to tocopherol, but it was considerably stronger at certain doses. In rats, administration of C. sativus stigma extract (100 mg/kg) for 7 days before induction of cerebral ischemia by middle cerebral artery occlusion (MCAO) significantly lowered SOD, catalase, and Na/K-ATPase activities, as well as glutamate and aspartate concentrations [116]. In PC12 cells, treatment with saffron extract (5 and 25 mg/mL) and crocin (10 and 50 M) reduced the neurotoxic impact of glucose [117]. ...
Article
Full-text available
The present review is designed to measure the effects of saffron extract in functional foods and its pharmacological properties against various disorders. Saffron is a traditional medicinal plant that is being used as food additive. The stigma of saffron has bioactive compounds such as safranal, crocin, crocetin, picrocrocin, kaempferol and flavonoid. These bioactive compounds can be extracted using conventional (maceration, solvent extraction, soxhlet extraction, and vapor or hydro-distillation) and novel techniques (emulsion liquid membrane extraction, ultrasound-assisted extraction, enzyme-associated extraction, pulsed electric field extraction, microwave-assisted extraction and supercritical fluid extraction). Saffron is used as a functional ingredient, natural colorant, shelf-life enhancer, and fortifying agent in developing different food products. The demand for saffron has been increasing in the pharma industry due to its protection against cardiovascular and Alzheimer's disease and its antioxidant, anti-inflammatory, antitumor and antidepressant properties. Conclusively, the phytochemical compounds of saffron improve the nutrition value of products and protect humans against various disorders
... At the supraspinal level, haloperidol did not modify the central anti-nociceptive effect of CSSE (Figure 6d), which implies that CSSE analgesic activity in the brain certainly did not involve D2 receptors, although it may still act on the dopamine system but through other mechanisms. This assumption was supported by previous reports on saffron's effect on the brain [80,81]. It has been reported that brain dopamine concentration is increased by saffron [80]. ...
... This assumption was supported by previous reports on saffron's effect on the brain [80,81]. It has been reported that brain dopamine concentration is increased by saffron [80]. In line with this report, Monchaux De Oliveira et al. [81] recently established that the saffron-induced improvement of depressive-like behavior was associated with the modulation of monoaminergic neurotransmission, in particular changes in serotonergic and dopaminergic neurotransmission. ...
Article
Full-text available
Saffron is the most expensive spice in the world. In addition to its culinary utilization, this spice is used for medicinal purposes such as in pain management. In this study, the analgesic activity of Crocus sativus stigma extract (CSSE) was evaluated in rodents and its possible physiological mechanism was elucidated. The anti-nociceptive effect of CSSE was evaluated using three animal models (hot plate, writhing, and formalin tests). The analgesic pathways involved were assessed using various analgesia-mediating receptors antagonists. The oral administration of CSSE, up to 2000 mg/kg, caused no death or changes in the behavior or in the hematological and biochemical blood parameters of treated animals nor in the histological architecture of the animals' livers and kidneys. CSSE showed a central, dose-dependent, anti-nociceptive effect in response to thermal stimuli; and a peripheral analgesic effect in the test of contortions induced by acetic acid. The dual (central and peripheral) analgesic effect was confirmed by the formalin test. The anti-nociceptive activity of CSSE was totally or partially reversed by the co-administration of receptor antagonists, naloxone, atropine, haloperidol, yohimbine, and glibenclamide. CSSE influenced signal processing, by the modulation of the opioidergic, adrenergic, and muscarinic systems at the peripheral and central levels; and by regulation of the dopaminergic system and control of the opening of the ATP-sensitive K+ channels at the spinal level. The obtained data point to a multimodal mechanism of action for CSSE: An anti-inflammatory effect and a modulation, through different physiological pathways, of the electrical signal generated by the nociceptors. Further clinical trials are required to endorse the potential utilization of Moroccan saffron as a natural painkiller.
... Studies have shown that TBI results in dopaminergic [75] cell loss leading to higher impulsivity and aggressivity [76]. Treatment with saffron extract has been shown to increase brain dopamine concentration [77]. This could explain the possible role of saffron in restoring dopamine dysfunction following injury. ...
Article
Full-text available
Traumatic brain injury (TBI) has the highest mortality rates worldwide, yet effective treatment remains unavailable. TBI causes inflammatory responses, endoplasmic reticulum stress, disruption of the blood–brain barrier and neurodegeneration that lead to loss of cognition, memory and motor skills. Saffron (Crocus sativus L.) is known for its anti-inflammatory and neuroprotective effects, which makes it a potential candidate for TBI treatment. Zebrafish (Danio rerio) shares a high degree of genetic homology and cell signaling pathways with mammals. Its active neuro-regenerative function makes it an excellent model organism for TBI therapeutic drug identification. The objective of this study was to assess the effect of saffron administration to a TBI zebrafish model by investigating behavioral outcomes such as anxiety, fear and memory skills using a series of behavioral tests. Saffron exhibited anxiolytic effect on anxiety-like behaviors, and showed prevention of fear inhibition observed after TBI. It improved learning and enhanced memory performance. These results suggest that saffron could be a novel therapeutic enhancer for neural repair and regeneration of networks post-TBI.
... This can lead to anti-anxiety and sedative effects and thereby reduce the morphine withdrawal signs [37]. As CSAE can increase the dopamine level in the brain of rats [41], probably, dopamine decreases the release of norepinephrine through its interaction with D2 receptors in nucleus accumbence and thus decrease in norepinephrine release can alleviate morphine withdrawal signs [37]. ...
Article
Full-text available
The purpose of this study is to evaluate the effect of Afghan Ferula assa-foetida L. and Crocus Sativus L. aqueous extracts either alone or in combination on morphine withdrawal signs. For this purpose, rats were randomly divided into 13 groups (1 Normal, 1 Morphine, 4 Ferula assa-foetida-treated groups, 4 Crocus sativus-treated groups, and 3 combination groups). Morphine dependency was rendered by subcutaneous injection of morphine hydrochloride for 4 days (10, 20 and 40 mg/kg doses twice daily for 3 days and a single dose of 60 mg/kg on 4th day). Various doses of extracts were injected into extract groups simultaneously with morphine. After two hours of last morphine administration, withdrawal signs were induced by naloxone (3 mg/kg) and noted for 30 minutes. According to the results, different doses of Ferula assa-foetida and Crocus sativus extracts and their combination (in low dose) could significantly decrease the number of morphine withdrawal signs (P<0.05). However, the combination of Ferula assa-foetida and Crocus sativus extracts in high doses showed toxic effects. In conclusion, Ferula assa-foetida and Crocus sativus extract combination in low dose can decrease the morphine withdrawal signs, but without any synergic effects.
Thesis
Les troubles dépressifs représentent un problème majeur de santé publique dont l’incidence ne cesse d’augmenter dans le monde. Ceci peut s’expliquer par le taux croissant d’individus ne répondant pas aux traitements antidépresseurs (ADs) conventionnels, mais également par la recrudescence de pathologies, souvent à composante inflammatoire, connues pour être associées à un risque accru de comorbidités neuropsychiatriques. De plus, une large proportion de patients déprimés développe des effets secondaires fortement invalidants. Ces problèmes soulignent la nécessité d'identifier des stratégies alternatives aux traitements pharmaceutiques actuels. L'utilisation d’interventions nutritionnelles peut alors être une solution de premier choix. En effet, certains nutriments et extraits de plantes ont des propriétés bioactives et peuvent ainsi moduler de nombreux systèmes neurobiologiques, dont ceux impliqués dans la physiopathologie des troubles dépressifs, tout en réduisant les effets secondaires. Dans ce contexte, le safran représente un candidat prometteur dans la prévention et le traitement des troubles dépressifs. En effet, des études cliniques et précliniques ont déjà montré une amélioration de la symptomatologie dépressive après administration d’actifs de safran, mais les mécanismes sous-tendant ces propriétés bénéfiques sont encore largement inconnus. Mieux les comprendre est pourtant essentiel afin de valider la pertinence thérapeutique d’interventions nutritionnelles avec des extraits de safran. En outre, il est important d’identifier les personnes qui pourraient être les plus à même d’en bénéficier. Les patients présentant une faible réponse thérapeutique aux ADs classiques pourraient alors être les premiers concernés. Diverses données récentes suggèrent l’implication de processus inflammatoires non seulement dans le développement des troubles dépressifs, mais aussi dans la mauvaise réponse aux ADs. Dès lors, cibler l'inflammation apparait comme une stratégie de choix pour améliorer la réponse clinique. De manière intéressante, plusieurs études ont mis en évidence des propriétés immunomodulatrices du safran, suggérant qu’il pourrait améliorer la réponse thérapeutique chez les patients dépressifs présentant un profil inflammatoire. Dans ce contexte, l’objectif général de ce travail de thèse a donc été de préciser le rôle d’interventions nutritionnelles basées sur des apports en safran dans la prise en charge des troubles dépressifs et d’en déterminer quels en sont les mécanismes. Pour cela, nous avons dans un premier temps mis en évidence les effets bénéfiques du safran sur les comportements de type dépressif induits notamment dans des conditions modélisant différents facteurs de risque de la dépression, tels que le stress. Les résultats neurobiologiques obtenus suggèrent qu’il agirait en ciblant en particulier les systèmes monoaminergiques centraux et la voie de la kynurénine. Dans un second temps, nous avons validé une approche expérimentale innovante basée sur l’utilisation de deux modèles murins de dépression différant par leurs mécanismes physiopathologiques, notamment en ce qui concerne les processus inflammatoires et permettant ainsi d’en étudier l’implication dans le développement et le traitement des troubles dépressifs. En conclusion, ce travail de thèse a permis d’établir des preuves précliniques de l’efficacité d’un extrait de safran dans la prise en charge des troubles dépressifs et de commencer à élucider les mécanismes d’action impliqués. Il a également validé une approche expérimentale adaptée à l’étude approfondie des mécanismes sous-jacents à la dépression inflammatoire, et qui devrait, à terme, permettre de mieux caractériser les populations susceptibles de bénéficier des approches nutritionnelles, en substitution ou en complément des traitements pharmaceutiques, sur la base de leur profil clinique. Ces travaux devraient donc contribuer à améliorer la prise en charge et le traitement des troubles dépressifs.
Article
Full-text available
Central nervous system (CNS) disorders and diseases are expected to rise sharply in the coming years, partly because of the world’s aging population. Medicines for the treatment of the CNS have not been successfully made. Inadequate knowledge about the brain, pharmacokinetic and dynamic errors in preclinical studies, challenges with clinical trial design, complexity and variety of human brain illnesses, and variations in species are some potential scenarios. Neurodegenerative diseases (NDDs) are multifaceted and lack identifiable etiological components, and the drugs developed to treat them did not meet the requirements of those who anticipated treatments. Therefore, there is a great demand for safe and effective natural therapeutic adjuvants. For the treatment of NDDs and other memory-related problems, many herbal and natural items have been used in the Ayurvedic medical system. Anxiety, depression, Parkinson’s, and Alzheimer’s diseases (AD), as well as a plethora of other neuropsychiatric disorders, may benefit from the use of plant and food-derived chemicals that have antidepressant or antiepileptic properties. We have summarized the present level of knowledge about natural products based on topological evidence, bioinformatics analysis, and translational research in this review. We have also highlighted some clinical research or investigation that will help us select natural products for the treatment of neurological conditions. In the present review, we have explored the potential efficacy of phytoconstituents against neurological diseases. Various evidence-based studies and extensive recent investigations have been included, which will help pharmacologists reduce the progression of neuronal disease.
Article
Full-text available
Saffron, a Crocus sativus L. derivative, has been recognized for its medical benefits since ancient times. Besides being an active flavoring and coloring agent in several food items, saffron has primarily been known for its pharmacological properties. Its major metabolites like crocin, picrocrocin, and safranal have been studied in vivo and in vitro as active pharmaceutical agents for inflammation, depression, microbial infections, and cancer-like diseases. These phytochemicals are well known for targeting the etiology of various diseases, making them an essential plant derivative in modern times. Moreover, research has shown saffron with several toxicological consequences as well. Numerous experimental and clinical studies have been conducted to determine the toxicity and safety of saffron. Saffron extract, safranal, and crocin have little or no acute toxicity. Organ toxicity has been detected at high dosages during sub-acute exposure. The teratogenic effects of saffron and its components have been particularly noted at high concentrations. This review provides a comprehensive outlook on the pharmacological attributes of saffron and its derivatives, besides highlighting their associated toxicity.
Article
Full-text available
Background and Objective: The effects of Crocus sativus (Saffron) on the euphoric properties of morphine have not yet been studied. In the present study, the effects of water extract of C sativus stigma on the acquisition and expression of morphine-induced Conditioned Place Preference (CPP) in male N-MARI mice (weighted 20-25 g) were investigated. Materials and Methods: This experimental study was conducted on 136 male mice that were divided into 17 groups (n=8/group). In a pilot study, different doses of morphine (1, 2, 4 and 8 mg/kg) and C. sativus extract (10, 50 and 100 mg/kg) were injected to the animals, to evaluate the drugs ability in induction of place preference. In the second phase of the experiments, the extract of the C. satjvus was administered during or after induction of morphine CPP. Then, CPP were tested in the animals. One-way analysis of variance (ANOVA) was performed for statistical procedure. Results: Administration of morphine (1, 2, 4 and 8 mg/kg), increased the required time in the compartment paired with morphine (i.e. CPP) that was significant (p<0.001) for those animals that received 4 and 8 mg/kg of morphine. Administration of the plant extract (50 mg/kg) also produced a significant CPP (p<0.01) compared with control group. Injection of the same dose of the extract before morphine (8 mg/kg) administration, caused a decrease in the time spent in drug-paired side only in dose of 100 mg/kg of the extract (p<0.05). In addition, injection of the plant extract in the test days to the animals, which reveived morphine (8 mg/kg) in the conditioning days, enhanced the expression of morphine CPP in the animals, that was statistically significant for the extract at the concentration of 50 mg/kg (p<0.05). Conclusion: It could be concluded that injection of the extract of C sativus can inhibit the acquisition but enhanced the expression of morphine-induced CPP. In addition, the extract can produce CPP by itself.
Article
Extracts from saffron are used for treatment of cancer and depression. Because of known quality problems HPLC methods on RP18 2.5µm and monolitic RP18 material were developed for quality control including the quantification of crocins 1 to 5, crocetin, picrocrocin and the degradation products cis-crocins. A GC-MS method allowed detection and quantification of the volatile compounds from saffron pentane extract. Both systems together allowed comprehensive characterization of saffron herbal material and extracts for clinical/preclinical trials. Based on a wide analytical survey of saffron from the global market a specification for high-quality saffron of >20% crocins, >6% picrocrocin and not less than 0.3% of volatiles, calculated as sum of safranal, isophorone and ketoisophorone, was developed. Because no detailed pharmacological effects are available to explain the clinical effects of saffron for treatment of cancer and depression receptor binding studies were performed. Saffron extracts and crocetin had clear binding capacity at the PCP binding side of NMDA receptor and at the sigma-1 receptor, while the crocin isomers and picrocrocin were not effective. These data give biochemical support for the above mentioned pharmacological effects of saffron.
Article
In the present study, the effects of crocin, an active component of Crocus sativus, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in mice were investigated. Subcutaneous administration of morphine (40 mg/kg for four days) produced place preference. Intraperitoneal administration of crocin (600 mg/kg for four days) 30 min before the morphine administration decreased the acquisition of morphine CPP. In other groups of animals, following extinction of a place preference induced by morphine (40mg/kg), single administration of morphine (10mg/kg) reinstated the place reference. Crocin (400 and 600 mg/kg) 30 min before this priming dose of morphine blocked morphine-induced reinstatement of place preference. These results showed that crocin can reduce the acquisition and reinstatement of morphine-induced conditioned place preference.
Article
Background: Experiments indicated that Crocus sativus L. extract may have an interaction with morphine. The effects of C. sativus on the euphoric properties of morphine in female mice did not studied. Objective: In the present study, the effects of water extract of C. sativus stigma on the acquisition and expression of morphine-induced conditioned place preference (CPP) in female N-MARI mice (20-25 g) were investigated. Methods: This experimental study was conducted on the 136 female fice that were divided in 17 groups (n=8/group). In a pilot study, different doses of morphine (1, 10 and 20 mg/kg) and the extract (10, 50 and 100 mg/kg) were injected to the animals for evaluation of the drugs ability to induction of place preference. In the second phase of the experiments, the extract of the C. sativus was administered during or after induction of morphine CPP. Then, CPP were tested in the animals. One-way Analysis of Variance (ANOVA) was proformed for statistical procedure. Results: Administration of morphine (1, 10 and 20 mg/kg), indcreased the time spend in the compartment paired with morphine (i.e. conditioned place preference-CPP). The increament was significant for the dose 10 and 20 mg/kg of morphine. Administration of the plant extract (50 mg/kg) also produced a significant CPP. Injection of the same doses of the extract before morphine (10 mg/kg) administration, caused a decrease in the time spent in drug-paired side in doses 50 and 100 mg/kg of the extract. In addition, injection of the plant extract in the test day to the animals in which reveived morphine (10 mg/kg) in the conditioning days decreased the expression of morphine CPP in the animals which was statisticaly significant for dose 10 mg/kg of the extract. Conclusion: It could be concluded that injection of the extract of C. sativus can inhibit the acquisition and expression of morphine-induced CPP. In addition, the extract produced CPP in female mice by it-self. These results indicated that saffron extract might be useful in morphine-induced psychological dependence in human as well.
Article
Background: The prevalance of opioid addiction is releativly high in Iran. Since the mechanism (s) of opioid addiction are not clear, this social problem is still remained unresolved. In the present study, the effects of water extract of Crocus sativus on the acquisition and expression of morphine-induced behavioral sensitization in female N-MARI mice (20-25 g) are investigated. Methods: Sensitization was induced by single injection of morphine (5 mg/kg) for three consecutive days followed by five days resting. On the 9th day of the experiments, the sensitization was assessed in animals by a single injection of very low dose of morphine (0.5 mg/kg). The extract of the C. sativus was administered during or after induction of morphine sensitization. Then, the sensitization were tested in the animals. In order to evaluate the effects of the drugs on locomotor activity, morphine and the extract were administered to the animal in a pilot study. Results: Our findings show that administration of morphine (0.5, 5 and 50 mg/kg), induced a significant activity in animals. The increament was significant for the dose 50 mg/kg of morphine. On the other hand, administration of the plant extract (10, 50 and 100 mg/kg) also produced a significant hyperactivity and hypoactivity in the animals. Preadministration of the animals by extract (10, 50 and 100 mg/kg, i.p.) reduced morphine effects. Injection of the same extract (10, 50 and 100 mg/kg) 30 min before the morphine (5 mg/kg) administration in the training days, caused a significant decrease in locomotor activity in animals, i.e. reduced the acquisition of morphine-induced behavioral sensitization. Injection of the plant extract (10, 50 and 100 mg/kg) in the test day, 30 min before morphine (0.5 mg/kg) administration also reduced the locomotor activity in the animals, i.e. reduced the expression of morphine-induced behavioral sensitization. Conclusion: It can be concluded that the extract of C sativus may inhibit morphine-induced hyperactivity and also acquisition and expression of morphine-induced behavioral sensitization in female mice which could be also usefull in human.
Article
In this review, we introduce the traditional uses of saffron and its pharmacological activities as described by either Avicenna in Book II, Canon of Medicine (al-Qanun fi al-tib) or from recent scientific studies. Modern pharmacological findings on saffron are compared with those mentioned in Avicenna's monograph. A computerized search of published articles was performed using MEDLINE, Scopus and Web of Science databases as well as local references. The search terms used were saffron, Crocus sativus, crocin, crocetin, safranal, picrocrocin, Avicenna and 'Ibn Sina'. Avicenna described various uses of saffron, including its use as an antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilatory, aphrodisiac, inducer of labour, emmenagogue and others. Most of these effects have been studied in modern pharmacology and are well documented. The pharmacological data on saffron and its constituents, including crocin, crocetin and safranal, are similar to those found in Avicenna's monograph. This review indicates that the evaluation of plants based on ethnobotanical information and ancient books may be a valuable approach to finding new biological activities and compounds. Copyright © 2012 John Wiley & Sons, Ltd.