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Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials

Authors:

Abstract

Chemoprevention strategies are very attractive and have earned serious consideration as potential means of controlling the incidence of cancer. An important element of anticancer drug development using plants is the accumulation and analysis of pertinent experimental data and purported ethnomedical (folkloric) uses for plants. The aim of this review is to provide an updated overview of experimental in vitro and in vivo investigations focused on the anticancer activity of saffron (Crocus sativus L.) and its principal ingredients. Potential use of these natural agents in cancer therapy and chemopreventive trials are also discussed. A computerized search of published articles was performed using the MEDLINE database from 1990 to 2004. Search terms utilized including saffron, carotenoids, chemoprevention, and cancer. All articles were obtained as reprints from their original authors. Additional sources were identified through cross-referencing. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients, possible mechanisms for these activities are discussed. More direct evidence of anticancer effectiveness of saffron as chemopreventive agent may come from trials that use actual reduction of cancer incidence as the primary endpoint This work suggests that future research be warranted that will define the possible use of saffron as effective anticancer and chemopreventive agent in clinical trials.
Review
Biomedical properties of saffron and its potential use in
cancer therapy and chemoprevention trials
F.I. Abdullaev PhD
a,
*, J.J. Espinosa-Aguirre PhD
b
a
Laboratorio Oncologı
´a Experimental, Instituto Nacional de Pediatrı
´a, Avenida Ima
´n#1TorredeInvestigacio
´n,
04530 Me
´xico D.F., Me
´xico
b
Instituto de Investigaciones Biome
´dicas, UNAM, Apartado Postal 70228, Ciudad Universitaria, Me
´xico D.F., Me
´xico
Accepted 2 September 2004
Abstract
Introduction: Chemoprevention strategies are very attractive and have earned serious consideration as potential means of controlling the
incidence of cancer. An important element of anticancer drug development using plants is the accumulation and analysis of pertinent
experimental data and purported ethnomedical (folkloric) uses for plants. The aim of this review is to provide an updated overview of
experimental in vitro and in vivo investigations focused on the anticancer activity of saffron (Crocus sativus L.) and its principal ingredients.
Potential use of these natural agents in cancer therapy and chemopreventive trials are also discussed.
Methods: A computerized search of published articles was performed using the MEDLINE database from 1990 to 2004. Search terms utilized
including saffron, carotenoids, chemoprevention, and cancer. All articles were obtained as reprints from their original authors. Additional
sources were identified through cross-referencing.
Results: Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities
of saffron and its main ingredients, possible mechanisms for these activities are discussed. More direct evidence of anticancer effectiveness of
saffron as chemopreventive agent may come from trials that use actual reduction of cancer incidence as the primary endpoint
Conclusions: This work suggests that future research be warranted that will define the possible use of saffron as effective anticancer and
chemopreventive agent in clinical trials.
#2004 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.
Keywords: Saffron (Crocus sativus); Cancer chemoprevention; Cytotoxicity; Clinical trials
Contents
1. Introduction . . . ........................................................................... 427
2. Methods . . ............................................................................... 427
3. Results . . . ............................................................................... 427
3.1. Description . . . ....................................................................... 427
3.1.1. History and folk use .............................................................. 427
3.1.2. Chemical composition. . . .......................................................... 428
3.2. Medical–biological activities of saffron . ...................................................... 428
3.2.1. Toxicity....................................................................... 428
3.2.2. Precautions . ................................................................... 428
3.2.3. Effect on coronary artery disease . . . .................................................. 428
www.elsevier.com/locate/cdp
Cancer Detection and Prevention 28 (2004) 426–432
* Corresponding author. Tel.: +52 55 10 84 09 00x1474; fax: +52 55 10 84 38 83.
E-mail addresses: fikrat@sni.conacyt.mx, fikrat@servidor.unam.mx, fikrat@yahoo.com (F.I. Abdullaev).
0361-090X/$30.00 #2004 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.cdp.2004.09.002
3.2.4. Effect on learning behavior and long-term potentiation . . . ................................... 428
3.2.5. Effects on ocular blood ow and retinal function . . . ....................................... 428
3.2.6. Effect on blood pressure . . . ........................................................ 428
3.2.7. Anticonvulsant effect . ............................................................ 428
3.2.8. Antinociceptive and anti-inammatory effects ............................................ 428
3.2.9. Mutagenic or antimutagenic effects . . . ................................................ 428
3.2.10. Antigenotoxic effect . . ............................................................ 429
3.2.11. Tumoricidal effect . . . ............................................................ 429
3.2.12. Cytotoxic effect . ................................................................ 429
4. Conclusions. . ............................................................................. 430
Acknowledgements ............................................................................. 431
References . . ................................................................................. 431
1. Introduction
Since immemorial times, herbal plants have been used in
virtually every culture throughout the world as a source of
folk medicine [1,2]. Over two millennia ago, the father of
medicine Hippocrates mentioned about 400 medicinal
plants and advised, ‘‘let food be your medicine and let
medicine be your food’’ [1]. It is still true today and suggests
that prevention is more important than treatment. Currently,
chemoprevention strategies are very attractive and have
earned serious consideration as a potential means of
controlling the incidence of cancer [2]. Scientists and
medical professionals have shown increased interest in this
eld, as they recognize the true health benets of natural
remedies. An important element of chemopreventive drug
development using plants is the accumulation and analysis
of pertinent experimental data and purported ethnomedical
(folkloric) uses for plants. It is also very important to
note that suitable chemopreventive natural agents should
have little or no toxicity, a high efcacy, to be orally
administrable, to have a known mechanism of action and of
low cost [3]. The present study provides an updated
overview of experimental in vitro and in vivo investigations
on the biological activities of saffron (Crocus sativus L.)
and its principal ingredients, especially focusing on their
anticancer effect. Potential use of these natural agents in
cancer therapy and chemoprevention trials is also discussed.
2. Methods
A computerized search of published articles was
performed using the MEDLINE database from the period
of 19902004. This database, produced by the National
Library of Medicine (NLM), includes all medico-biological
literature dated from 1974 and so on. Depending on the
literature period of interest, it is offered either on-line or off-
line. Input data are obtained from approximately 3000
journal titles comprising of life sciences and/or medical
information. Approximately, 99% of the data included in
the database le are journal articles, of which, 65% are in
the English language. The remaining 1% of data represent
government documents. Retrieval provides bibliographic
data with an abstracted summary, obtained by using
keywords and/or subject headings. The search terms utilized
including saffron, carotenoids, chemoprevention, and
cancer. All articles were obtained as reprints from their
original authors. Additional sources were identied through
cross-referencing.
3. Results
3.1. Description
Saffron (Crocus sativus) is a bulbous perennial of the iris
family (Iridaceae) treasured for its golden-colored, pungent
stigmas, which are dried and used to avor and color foods
as well as a dye. Saffron is a spice known only in cultivation
and principally grown in Spain and Iran, but also cultivated
on a lower scale in Greece, Turkey, India, Azerbaijan,
France, Italy, India, China, Morocco, Turkey, Israel, Egypt,
United Arab Emirates, Mexico, Switzerland, Algeria,
Australia, and New Zealand [4,5].
3.1.1. History and folk use
The name saffron comes from the Arabic zafaran, which
means yellow. The use of saffron also goes back to ancient
Egypt and Rome, where it was used as a dye, in perfumes,
and as a drug as well as for culinary purposes [6,7].Asa
medicinal plant, saffron has traditionally been considered an
anodyne, antidepressant, a respiratory decongestant, anti-
spasmodic, aphrodisiac, diaphoretic, emmenagogue, expec-
torant, and sedative. It was used in folk remedy against
scarlet fever, smallpox, colds, asthma, eye and heart disea-
ses, tumor, and cancer. Saffron can also be used topically to
help clear up canquer sores and to reduce the discomfort of
teething infants [4,5].
F.I. Abdullaev, J.J. Espinosa-Aguirre/ Cancer Detection and Prevention 28 (2004) 426432 427
3.1.2. Chemical composition
The stigmas of the saffron ower contain many chemical
substances. Carbohydrates, minerals, musilage, Vitamins
(especially riboavin and thiamine) and pigments including
crocin, anthocianin, carotene, lycopene, zigzantin, avo-
noids, amino acids, proteins, starch, gums, and other
chemical compounds have also been described in saffron
[47].
The saffron stigma, which is what basically forms
commercial saffron, has a distinct and unique color, avor
and aroma and some of the groups of chemical compounds
responsible for each of these properties have now been
identied. One of its principal coloring pigments is crocin,
which is easily soluble in water. In addition to crocin, saffron
contains crocetin as a free agent and small amounts of the
pigment anthocianin, a-carotene, b-carotene, and zegxantin
[5,8].
The principal element giving saffron its special ‘‘bitter’’
avor is the glycoside picrocrocin. This bitter tasting
substance can be crystallized and produces glucose and the
aldehyde safranal by hydrolysis [5,8].
The main aroma factor in saffron is safranal, which
comprises of about 60% of the volatile components of
saffron. In fresh saffron, this substance exists as a stable
picrocrocin but as a result of heat and with the passage of
time, it decomposes releasing the volatile aldehyde, safranal
[5,8].
3.2. Medicalbiological activities of saffron
3.2.1. Toxicity
The toxicity of saffron has been found to be quite low.
Animal studies indicate that the oral LD
50
of saffron was
20.7 g/kg administrated as a decoction [5].
3.2.2. Precautions
Saffron should always be obtained from a reputable
source that observes stringent quality control procedures and
industry-accepted good manufacturing practices. People
with chronic medical conditions should consult with their
physician before taking the herb. Pregnant women should
never take the herb for medicinal purposes, as saffron can
stimulate uterine contractions [9].
3.2.3. Effect on coronary artery disease
Fifty milligrams of saffron dissolved in 100 ml of milk
was administered twice a day to human subjects as reported
in an Indian study published in 1998. The signicant
decrease in lipoprotein oxidation susceptibility in patients
with coronary artery disease (CAD) indicates the potential
of saffron as an antioxidant [10].
3.2.4. Effect on learning behavior and long-term
potentiation
Several Japanese studies have reported that the saffron
extract and two of its main ingredients crocin and crocetin,
improved memory and learning skills in ethanol-induced
learning behavior impairments in mice and rats [1116].
These results suggest that oral administration of saffron may
be useful as treatment for neurodegenerative disorders and
related memory impairment. Recently, it was shown that
crocin isolated from saffron exhibits anti-apoptotic action in
PC-12 cells treated with daunorubicin [17]. These ndings
suggest that crocin inhibits neuronal death induced by both
internal and an external apoptotic stimulus in highly
differentiated cells (neurons). This selective behavior
suggests important therapeutic implications, related to the
fact that programmed cell death is reduced in cancer and
increased in neurodegenerative disease [17].
3.2.5. Effects on ocular blood ow and retinal function
It was shown that crocin analogs isolated from saffron
signicantly increased the blood ow in the retina and
choroid as well as facilitated retinal function recovery [18].
Authors suggest that crocin analogs could be used to treat
ischemic retinopathy and/or age-related macular degenera-
tion.
3.2.6. Effect on blood pressure
Recently, an Iranian study researches examined the
effects of saffron petal extract on blood pressure in
anesthetized rats and on responses of the isolated rat vas
deferens and guinea-pig ileum induced by electrical eld
stimulation (EFS). It was shown that aqueous and ethanol
extracts of saffron reduced the blood pressure in a dose-
dependent manner. EFS of the isolated rat vas deferens also
were decreased by these saffron extracts [19].
3.2.7. Anticonvulsant effect
In Iranian traditional medicine, the saffron had been used
as an anticonvulsant remedy. Recently, in experiments with
mice using maximal electroshock seizure (MES) and
pentylenetetrazole (PTZ) tests, Iranian scientists have
demonstrated that the aqueous and ethanolic extracts of
saffron possess anticonvulsant activity. These authors
suggested that saffron extracts might be benecial in both
absence and tonic clonic seizures [20].
3.2.8. Antinociceptive and anti-inammatory effects
An Iranian experimental study with mice indicated that
saffron stigma and petal extracts exhibited antinociceptive
effects in chemical pain test as well as acute and/or chronic
anti-inammatory activity [21]. It was suggested that these
effects of saffron extracts might be due to their content of
avonoids, tannins, anthocyanins, alkaloids, and saponins
[22].
3.2.9. Mutagenic or antimutagenic effects
It was reported that crocin and dimethyl-crocetin isolated
from saffron were non-mutagenic [23]. Recently, data from
our laboratory, using the Ames/Salmonella test system
(strains TA97; TA98; TA100; TA102, and TA1538),
F.I. Abdullaev, J.J. Espinosa-Aguirre/ Cancer Detection and Prevention 28 (2004) 426432428
demonstrated that the saffron extract itself in concentration
up to 1500 mg/plate was non-toxic, non-mutagenic, and non-
antimutagenic [24,25].
3.2.10. Antigenotoxic effect
It was reported that the topical administration of saffron
extracts (100 mg/kg body weight) inhibited the initiation/
promotion of 7,12-dimethylbenz [a] anthracene (DMBA)-
induced skin tumors in mice, delaying the onset of papilloma
formation and reducing the mean number of papillomas per
mouse [26]. The oral administration of the same dose of
saffron extracts restricted tumor incidence of 20-methyl-
cholanthrene (MCA)-induced soft tissue sarcomas in mice
[23,26]. Extracts from saffron stigmas prolonged the life
span of cisplatin-treated mice and partially prevented the
decrease in body weight, leukocyte count and hemoglobin
levels [2729].
Pretreatment with the aqueous extract of saffron
(composed mainly by carotenoids) in experiments with
Swiss albino mice signicantly inhibited the genotoxicity of
cisplatin, cyclophosphamide, mitomycin, and urethane [30].
It was suggested that saffron rich in carotenoids might exert
its chemopreventive effects by the modulation of lipid
peroxidation, antioxidants, and detoxication systems [31].
Crocetin from saffron also ameliorates bladder toxicity of
the anticancer agent cyclophosphamide without altering its
antitumor activity [28].
The treatment of animals with cysteine (20 mg/kg body
weight) together with saffron extract (50 mg/kg body
weight) signicantly reduced the toxic effects caused by
cisplatin, such as nephrotoxicity and changes in enzyme
activity [32].
3.2.11. Tumoricidal effect
It has been previously shown that saffron was more active
parenterally than by oral route, and oral administration
might be improved by the liposome encapsulation of the
drug. It was reported that the liposome encapsulation of
saffron produced a signicant inhibitory effect on the growth
of transplanted tumor cells in mice [33]. Recently, in an
animal model (frog embryos), it was demonstrated that
crocetin, isolated from saffron was effective in treating
certain types of cancer treatable with all-trans retinoic acids
(ATRA). It was suggested that crocetin might also be a safer
alternative to treat ATRA-sensitive cancers in women of
childbearing age [34].
The oral administration of the saffron ethanolic extract
increased the life span of Swiss albino mice intraperitoneally
transplanted with sarcoma-180 (S-180) cells, Ehrlich ascites
carcinoma (EAC) or Daltons lymphoma ascites (DLA)
tumors. The authors did not identify the exact nature of the
active compound from saffron stigmas, but suggested that
this compound showed the presence of glycosidic linkage.
Liposome encapsulation of saffron effectively enhanced its
antitumor activity against S-180 and EAC solid tumors in
mice, promoting signicant inhibition in the growth of these
tumors [35,36]. On the other hand, in the presence of the T
cell mitogen phytohemagglutinin, saffron stimulated non-
specic proliferation of lymphocytes in vitro [36], suggest-
ing that the antitumor activity might be immunologically
mediated. Another study [37] examined the effects of long-
term treatment with crocin on tumor growth and life span of
rats bearing colorectal tumors, induced by rat adenocarci-
noma DHD/K12-PROb cells injected subcutaneously.
Crocin treatment signicantly increased their survival time
and decreased tumor growth rate, more intensely in females.
The selective action of crocin in female rats as compared
with male rats suggests that the effects of crocin in animals
might be partially dependent on hormonal factors. An
increase in the levels of b-carotene and Vitamin A in the
serum of laboratory animals under oral administration of
saffron extracts was detected [32]. It was suggested that
saffron carotenoids possessed provitamin A activity
according to the hypothesis that the action of carotenoids
was dependent upon its conversion to retinal (Vitamin A),
because most of the evidence supporting the anticancer
effects of carotenoids were referred to b-carotene [38].
3.2.12. Cytotoxic effect
Incubation of HeLa cells (derived from a cervical
epitheloid carcinoma) with ethanolic saffron extract resulted
in signicant inhibition of colony formation and cellular
DNA and RNA synthesis, with 50% inhibition obtained at
concentrations from 100 to 150 mg/ml, whereas inhibition of
protein synthesis was not detected even at high extract
concentrations [39]. In other study on the effect of the
ethanolic saffron extract on macromolecular synthesis in
three human cell lines: A549 cells (derived from a lung
tumor), WI-38 cells (normal lung broblasts) and VA-13
cells (WI-38 cells transformed by SV40 virus), it was found
that the malignant cells were more sensitive than the normal
cells to the inhibitory effects of saffron on both DNA and
RNA synthesis [40]. It has been suggested that the inhibitory
effect on cellular DNA and RNA synthesis, but not on
protein synthesis, is one of the main mechanisms of action
for saffrons antitumor and anticarcinogenic activities
[5,36,3941]. The inhibitory effect of crocetin, isolated
from saffron, on intracellular nucleic acid and protein
synthesis in three malignant human cell lines, HeLa, A549
(lung adenocarcinoma), and VA13 (SV-40 transformed
foetal lung broblasts) was reported [41]. Crocetin caused a
dose-dependent inhibition of nucleic acid and protein
synthesis, but had no effect on colony formation. Other
studies described the inhibition of growth of human chronic
myelogenous leukaemia K562 and promyelocytic leukae-
mia HL-60 cells by dimethyl-crocetin, crocetin, and crocin
with 50% inhibition (ID
50
) reached at concentrations of 0.8
and 2 mM, respectively, [38,42]. Cytotoxicity of dimethyl-
crocetin and crocin to various tumors cell lines (DLA, EAC,
S-180, L1210 leukemia, and P388 leukemia) and to human
primary cells from surgical specimens (osteosarcoma,
brosarcoma, and ovarian carcinoma) has been reported.
F.I. Abdullaev, J.J. Espinosa-Aguirre/ Cancer Detection and Prevention 28 (2004) 426432 429
These authors also detected signicant inhibition in the
synthesis of nucleic acids, and suggested that dimethyl-
crocetin could disrupt DNA-protein interactions (e.g.
toposiomerases II) important for cellular DNA synthesis
[26,36].
The inhibitory effect of the ethanolic saffron extract on
the in vitro growth of HeLa cells (ID
50
= 2.3 mg/ml) was
mainly due to crocin (ID
50
of 3 mM), where picrocrocin and
safranal, with an ID
50
of 3 and 0.8 mM, respectively, played
a minor role in the cytotoxicity of saffron extracts [43].It
was suggested that sugars might play a key role in cytotoxic
effect of crocin, since its deglucosylated derivative crocetin
did not cause cell growth inhibition even at high doses.
These ndings are in accordance with the results [42], which
found no effect of crocetin on colony formation in HeLa
cells and two other solid tumor cell lines. However, they are
in disagreement with results from other authors who
reported cytotoxicity for crocetin against a cell line derived
from a non-solid tumor [38] and various tumor cell lines and
human primary cells from surgical specimen [34].AnID
50
of 0.4 and 1.0 mM was reported for crocin on the rat
adenocarcinoma DHD/K12-PROb cells and human colon
adenocarcinoma HT-29 cells, respectively [37].
In other study using saffron, ginsenoside, and cannabi-
noid derivatives to determine potential membrane-asso-
ciated antitumor effects of these substances, it was
demonstrated that saffron derivatives were ineffective on
the reversal of multidrug resistance of lymphoma cells (the
reversal of multidrug resistance is the result of the inhibition
of the efux pump function in the tumor cells) [44].
Microscopy studies revealed that HeLa cells treated with
crocin exhibited vacuolated areas, size reduction, cell
shrinkage, and piknotic nuclei [37,43], suggesting that
programmed cell death is induced by crocin, as was
previouly proposed by Morjani [42]. A remarkable bioactive
agent has been isolated from the corms of the saffron plant
[45,46]. This agent showed an ID
50
of 9 mg/ml against HeLa
cells. The cytotoxic activity of this agent on human
malignant cell lines (HeLa, breast carcinoma MDA-MB-
231, and brosarcoma HT-1080), a non-malignant cell line
(broblasts ASJ-4), and blood cells and hair follicles in
culture, was also analyzed. ID
50
values ranged from 7 to
22 mg/ml for tumor cells, and 100 mg/ml for normal
broblasts. Comparison of ID
50
values for brosarcoma
cells and normal broblasts, both of mesenchymal origin,
showed that this agent is near eight times more toxic on
tumor cells than on non-tumor cells [47].
4. Conclusions
Saffron Crocus sativus L. and their associated carotenoid
ingredients are extensively studied for their biomedical
properties, especially for their chemopreventive potential
against cancer, during the last decade [57,25,36,4850].
Since ancient times, saffron was used in folk medicine as an
anticancer agent against different kinds of tumors and
cancers [49,50]. In the early 1990s, Indian studies and our
own have demonstrated that crude saffron extracts present
antitumor and anticarcinogenic activities as well as
cytotoxic and antimutagenic effects [35,39,40]. A number
of in vivo and in vitro experiments discussed above and in
our recent review [5] clearly indicate that saffron and its
main ingredients have the potential to reduce the risk of
developing several types of cancer. Different hypotheses for
the mode of anticancer action of saffron and its ingredients
have been proposed (Table 1) and in detail discussed in our
previous review [5]. Recently, it was reported that three new
monoterpenoids and a new naturally occurring acid were
isolated from methanol extracts of the petals of saffron.
Among them, crocusatin H, crocin-1, and crocin-3 showed
signicant tirosine inhibitory activity [51,52]. Iranian
scientists have demonstrated that three L-lactate dehydro-
genase termostable isoenzymes were detected in saffron
corms [5354]. To date, the exact mechanism of anticancer
effect of saffron is not clear. However, all of the available
information from animal and in vitro studies indicated that
saffron and their main constituents possess anticancer and
antitumor activities. These ndings have not yet been
veried by clinical trials in humans. Comprehensive, in-
depth studies still need to be conducted to dene the
mechanisms involving in the therapeutic properties of
saffron and in addition to performing clinical trials in
humans. Indoor cultivation and modern biotechnological
F.I. Abdullaev, J.J. Espinosa-Aguirre/ Cancer Detection and Prevention 28 (2004) 426432430
Table 1
Proposed mechanism of chemopreventive agent actions
Chemopreventive agents Mechanism of action Reference
Saffron extract Inhibition of itracellular nucleic acid synthesis [4,5,34]
Saffron extract and its carotenoids ingredients Inhibition of free radical chain reaction [5,30,33,35]
Saffron extract Stability to irradiation [49]
Carotenoids Metabolic conversion of carotenoids to retinoids [5,38]
Carotenoids Reaction with topoisomerase II [33,35]
Carotenoids Blocked the cytochrome C activation of caspase-3 [21]
Saffron extract and its carotenoids ingredients Increase of intracellular SH compounds [33,38,39]
Saffron extract Inhibition of genotoxicity [29,3133]
Saffron extract and its carotenoids ingredients Induction of apoptosis [5,41,42]
Saffron extract and its carotenaoids ingredients Inhibition of different cellular enzymes activity [30,34,43]
Saffron extract and its carotenoids ingredients Inhibition of cell proliferation [5,35,37,42]
methods will prove advantageous in achieving the largest
amount and highest quality of saffron as well as in reducing
its cost of production. In the continued search for new anti-
tumor agents, investigators dedicate their efforts to the study
of natural compounds and their effects in modifying cancer
risks, delaying carcinogenesis, or inhibiting tumor forma-
tion. This work suggests that future research be guaranteed
to evaluate the possible use of saffron as an effective
anticancer agent in clinical trials.
Acknowledgement
This work was partially supported by funds from
CONACyT (Grant 40011).
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... The main effects of saffron are attributed to its main componentscrocetin and its glycosidic esters, crocin, and safranal, and the synergy between the compounds in the spice, which have potent antioxidants anti-inflammatory effects and strengthen anabolic pathways as the supposed mechanism [28]. Additionally, saffron exhibited a variety of health benefits [29], such as analgesic and sedative properties [30], and acts as an anticancer [31,32] as well as anti-mental disorders [33] and anti-dementia agent [34]. ...
... It might be due to the low dose of saffron, low volume program of resistance training, and the short intervention period. Recently, it has been clearly stated that saffron has multiple putative biological activities [32,33,38,46] and has beneficial effects on the female reproductive system [48]. Furthermore, testosterone levels significantly increased in groups receiving high doses of saffron compared to the placebo group [49]. ...
Article
Full-text available
Objectives Multiple physiopathological conditions through stimulate atrogene led to trigger skeletal muscle atrophy, which the regulation of this signaling pathway is still not fully understood. In this study, researchers evaluated the assumptions that saffron extract and resistance training may inhibit muscle atrophy and Atrogene expression, increase testosterone concentration as well as weight in rats with dexamethasone (dex)-induced muscle atrophy. Study design We evaluated the effects of saffron extract and resistance training on atrophic markers in rats with dex-induced muscle atrophy using seven experimental groups. Methods 42 male SD (Sprague-Dawley) rats were randomly distributed into seven subgroups: (1) dex-control (cn), (2) dex-resistance training (tn), (3) dex-saffron feeding 20 mg/kg/day (sa 20 mg), (4) dex-saffron feeding 40 mg/kg/day (sa 40 mg), (5) dex-saffron feeding 20 mg/kg/day + resistance training (sa 20 mg + tn), (6) dex-saffron feeding 40 mg/kg/day + resistance training (sa 40 mg + tn), and (7) healthy control i.e. non-injected dex (cn-i). order to induce muscle atrophy, groups 1 to 6 were intraperitoneally injected with dexamethasone (750 μg/kg). The resistance training protocol and 20 and 40 mg/kg/day saffron treatments were carried out for 2 months. Results Total weight, soleus, and EDL muscles weight in dex + 20 and 40 mg Saffron, resistance training, resistance training + 20, and 40 mg Saffron groups were significantly increased compared to pre-experimental levels or the health control group (P < 0.05). The serum testosterone level was significantly increased in resistance training + 20 and 40 mg Saffron groups compared to the health control group (P < 0.05). The level of Atrogin-1, Murf-1, and Mir-29b gene expressions in soleus and EDL muscles was significantly elevated in resistance training + 20 and 40 mg Saffron groups compared to the health control group (P < 0.05). Conclusion These findings set saffron alongside resistance exercise as a new target in therapeutic approaches toward clinical conditions causing muscle mass loss.
... Crocus sativus L., also known as saffron, is a cultivated perennial plant from the Iridaceae family. These plants are grown in Iran, Turkey, and Spain and are used for cosmetics, food, and medical purposes (9,10). Some studies have shown that saffron and its components have anticarcinogenic, anti-inflammatory, and antidepressant properties (10)(11)(12)(13)(14)(15)(16). ...
... These plants are grown in Iran, Turkey, and Spain and are used for cosmetics, food, and medical purposes (9,10). Some studies have shown that saffron and its components have anticarcinogenic, anti-inflammatory, and antidepressant properties (10)(11)(12)(13)(14)(15)(16). In addition, crocin, safranal, and crocetin, which are the main constituents of saffron, and saffron have been proven to have antioxidant properties in many studies (17)(18)(19)(20)(21)(22). ...
... This plant mainly grows in some Mediterranean countries, India, and some regions in China, such as Tibet. The flower of this botanical contains a number of chemical constituents with therapeutic potential (19), and has thus been used as a folk medicine for a very long time. Saffron is a component that can be used as a spice for food flavoring and coloring and is derived from the stigma of the flower of the plant commonly known as the saffron crocus. ...
... Saffron (Crocus sativus L), a perennial stemless herb supposed to have some properties with significance in traditional medicine like antispasmodic, eupeptic, anticatarrhal, nerve sedative, carminative, diaphoretic, expectorant, stimulant, stomachic, aphrodisiac, and abortion [7]. Several pharmacological studies confirmed antioxidant, anticancer, anticonvulsant, anti-inflammatory and antitumor effects, radical-scavenging and learningand memory-improving properties of saffron [8][9]. The active constituents of saffron safranal (a volatile agent), crocetin, and its glycoside crocin dye material handle its pharmacological activities [10]. ...
... The appreciation for saffron spice as a food additive has been observed in the past and continues today, being considered the world's highest priced spice [19]. In addition, saffron continues to be used in the traditional medicine of many cultures [20,21]. Numerous studies have demonstrated its therapeutic properties, [22][23][24][25] increasing the demand of saffron for medical and cosmetic applications. ...
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Chromoplasts and chloroplasts contain carotenoid pigments as all-trans- and cis-isomers, which function as accessory light-harvesting pigments, antioxidant and photoprotective agents, and precursors of signaling molecules and plant hormones. The carotenoid pathway involves the participation of different carotenoid isomerases. Among them, D27 is a β-carotene isomerase showing high specificity for the C9-C10 double bond catalyzing the interconversion of all-trans- into 9-cis-β-carotene, the precursor of strigolactones. We have identified one D27 (CsD27-1) and two D27-like (CsD27-2 and CsD27-3) genes in saffron, with CsD27-1 and CsD27-3, clearly differing in their expression patterns; specifically, CsD27-1 was mainly expressed in the undeveloped stigma and roots, where it is induced by Rhizobium colonization. On the contrary, CsD27-2 and CsD27-3 were mainly expressed in leaves, with a preferential expression of CsD27-3 in this tissue. In vivo assays show that CsD27-1 catalyzes the isomerization of all-trans- to 9-cis-β-carotene, and could be involved in the isomerization of zeaxanthin, while CsD27-3 catalyzes the isomerization of all-trans- to cis-ζ-carotene and all-trans- to cis-neurosporene. Our data show that CsD27-1 and CsD27-3 enzymes are both involved in carotenoid isomerization, with CsD27-1 being specific to chromoplast/amyloplast-containing tissue, and CsD27-3 more specific to chloroplast-containing tissues. Additionally, we show that CsD27-1 is co-expressed with CCD7 and CCD8 mycorrhized roots, whereas CsD27-3 is expressed at higher levels than CRTISO and Z-ISO and showed circadian regulation in leaves. Overall, our data extend the knowledge about carotenoid isomerization and their implications in several physiological and ecological processes.
... Crocus sativus L., often known as saffron, is a perennial stemless herb in the Iridaceae family that is mostly farmed in Spain and Iran, but also in Greece, Turkey, Azerbaijan, France, Italy, India, and China on a lesser level [18]. In folk medicine, saffron was used as an antispasmodic, eupeptic, gingival sedative, anticatarrhal, nerve sedative, carminative, diaphoretic, expectorant, stimulant, stomachic, and aphrodisiac [19]. ...
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This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain’s MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.
... Crocus sativus L. (saffron) is a highly valued species owing to its unique qualities as a plant that provides color, taste, and flavor to the food as well as its medicinal properties (Abdullaev & Espinosa-Aguirre, 2004;Baba et al., 2015;Samarghandian et al., 2010). e natural color and aroma of saffron are derived from stigmas aer appropriate drying; the color is derived from crocin, whereas picrocrocin and safranal are responsible for the taste and aroma (Lahmass et al., 2018). ...
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Saffron ( Crocus sativus L., Iridaceae) is a highly valued species in the food, medicinal, and nutraceutical industries as a coloring, flavoring, and therapeutic agent. Its productivity and flower production vary depending on different factors, including fertilizer treatment. This study was conducted to evaluate the effects of inorganic (NK) fertilizer combined with organic matter in different plant densities as well as the influence of split foliar fertilizer application on flower yield of saffron. The performance of saffron plants revealed that the combined application of inorganic fertilizer NK and vegetal organic matter (1%) was generally better than the effect of foliar treatment. Treatment with split foliar fertilizers at the recommended optimal concentration prolonged the flowering period of saffron plants.
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Introduction: Evidence shows that secondary metabolites of saffron can be used in the formulation of new drugs for the treatment of various human cancers. It is demonstrated that saffron crocin inhibits the proliferation of cancer cells while having no inhibition effect on the growth of normal cells. Consumption of this substance also reduces the side effects of cancer chemotherapy. Therefore, the present study was performed to investigate the effect of crocin on the proliferation and apoptosis of breast cancer cells and determine its molecular mechanism. Material & Methods: Initially, MCF7 breast cancer cells were prepared from the Pasteur Institute of Iran Cell Bank and cultured in RPMI1640 medium with FBS 10%. To determine the effect of crocin toxicity on cancer cells, treatment was conducted at different concentrations and different hours, and (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was performed. The cell proliferation or cell apoptosis was evaluated as well. DAPI staining was performed to demonstrate cell apoptosis. After RNA extraction and cDNA preparation, the expression of an apoptosis-related gene (PTEN) and Akt pathway genes were measured by Real-time polymerase chain reaction (PCR) to determine the mechanism of the crocin effect. Findings: Results of the MTT assay showed that crocin inhibited the proliferation of MCF7 cells and induced apoptosis in these cells. In addition, real-time PCR results showed that crocin increased PTEN gene expression (P=0.041) in MCF7 breast cancer cells and significantly decreased Akt1 gene expression (P=0.038). Discussion & Conclusion: The results indicate that crocin stimulates the apoptotic cells in MCF7 breast cancer cells and can be used as a new therapeutic strategy for the treatment of breast cancer.
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Saffron is a spice derived from the flower of Crocus sativus L., which has a special aroma, colour and odour influencing positively its economic value. In this context, ten saffron ecotypes were screened for their biochemical composition and antioxidant activity. The samples were also analysed using GC‐MS and LC‐MS to determine their content of volatile and phenolic compounds, respectively. The results revealed statistically significant differences among samples based on moisture (9.09%‐11.23%), total phenols (31.62‐62.71 mg EAG/g), total flavonoids (23.02‐40.02 mg ER/mg), total carotenoids (66.12‐155.05 μg/g), picrocrocin (88.99‐121.53), crocin (137.44‐228.39) and safranal (26.56‐53.04). The radical scavenging activity ranged from 17.09% to 29.53% for DPPH assay, and oscillated from 0.128 mmol AAE/g to 0.239 mmol AAE/g for ABTS test, while the ferric reducing antioxidant potency (FRAP) varied from 0.974 to 1.989 mmol Fe2+/g. Gas chromatography‐mass spectrometry (GC‐MS) analysis identified 66 volatile compounds, among which the Safranal and Isophorone were the most abondant. The ES1 from Taliouine recorded a very distinct volatile composition compared to the others ecotypes with 22 authentic volatile compounds. Moreover, liquid chromatography‐ mass spectrometry (LC‐MS) analysis revealed 14 phenolic compounds with picrocrocin and crocin were found to be the major compounds. The principal component analysis classified the investigated ecotypes into two mean distinctive sets with ES1 and ES9 were distinguished as a single items. The α‐pinene, β‐pinene, limonene, anethole, acetic acid, ketoisophorone, isophorone, safranal, thymoquinone, total flavonoids, FRAP and total carotenoids, are the main discriminant variables. The two‐dimensional analysis of the clustered heatmaps divided showed a relatively similar patterns as the principal component analysis (PCA) and confirmed the singularity of the sample ES1 based on its particular volatile profile dominated mainly by α‐terpinyl acetate, methyleugenol, copaene, anethole, limonene, methyl‐cyclopentane, which were not identified in the other samples even at minor levels. These findings herein found revealed the high quality of Moroccan saffron, which is very important for the species breeding and valorization. Ten cultivars of saffron grown in Morocco were analysed in terms of their phytochemical composition as well as their antioxidant activities. In addition, GC‐MS and HPLC‐MS methods are also applied. Therefore, the aromatic potential, quality and antioxidant activity of the ten cultivars are determined.
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Background: Acetaminophen (APAP) is a common analgesic and antipyretic medicine that can lead to acute liver injury at high doses. Crocin, a Crocus sativus’ ingredient, has potent antioxidant effects. Objectives: This study examined the protective effects of crocin against APAP-induced oxidative stress in mice. Methods: In this study, 56 mice were randomly divided into seven groups (n = 8 per group), including the negative (normal saline, 10 mL/kg) and positive (oral normal saline for five days + a single dose of APAP (300 mg/kg) on day 6th) control groups. The third group (NAC) received normal saline for up to five days, and on the 6th day, immediately after the administration of acetaminophen, received NAC (50 mg/kg). Groups fourth to sixth received respectively 12.5, 25, and 50 mg/kg of crocin (orally for six days), followed by a single dose of APAP (300 mg/kg) on 6th day. The last group received crocin (50 mg/kg) for six days. Then 24 h after the last injection, the animals were sacrificed, and samples were collected for biochemical and histopathological evaluations. Results: The levels of ALT, AST, and MDA increased, and the activity of CAT, GSH, and GPX decreased in the APAP-treated group compared to the control group. In APAP-treated groups, the administration of crocin decreased the serum levels of AST, ALT, and MDA and increased the activity of CAT, GSH, and GPX. Histopathological evaluations confirmed the above findings. Conclusions: According to our results, it seems that crocin has a protective effect against acetaminophen-induced liver toxicity and can be used as a therapeutic agent to treat APAP-induced hepatotoxicity.
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In this work we have studied the volatile components of saffron, the dried, dark-red stigmata of Crocus sativus L. flowers. The isolation of the aroma, was achieved using the following techniques:  (a) steam distillation (SD), (b) micro-steam distillation extraction (MSDE), and (c) vacuum head space method (VHS). The determination of the volatile components was performed using some different gas chromatography−mass spectrometry (GC−MS) instruments and methods. The characteristic compounds are 2,6,6-trimethyl-1,3-cyclohexadien-1-carboxaldehyde, namely safranal; 3,5,5-trimethyl-2-cyclohexen-1-one, namely isophorone; 3,5,5-trimethyl-3-cyclohexen-1-one, isomer of isophorone; 2,6,6-trimethyl-2-cyclohexen-1,4-dione; and 2,6,6-trimethyl-1,4-cyclohexadiene-1-carboxaldehyde, isomer of safranal. Keywords: Saffron; capillary; GC−MS; volatile compounds
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This paper reviews the literature on recent research on the chemical composition and pharmacological activities of saffron (Crocus sativus) and its active constituents, mainly as antitumoral, hypolipidemic and tissue oxygenation enhancement agents.
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Background-Crocus sativus L. stigma (CSS) has sedative properties and is used in traditional medicine for its anticonvulsant property. Objective-We studied the anticonvulsant activity of the aqueous and ethanolic extracts of CSS in mice in order to evaluate the traditional use of this plant. Methods-The pentylenetetrazole (PTZ) and the maximal electroshock seizure (MES) tests were used for assessing the anticonvulsive effects of this plant. Results-In the PTZ test, CSS delayed the onset of tonic convulsions, but failed to produce complete protection against mortality. In the MES test, both extracts decreased the duration of tonic seizures. Conclusion-The results of this study indicate that the extracts of CSS may be beneficial in both absence and tonic clonic seizures.
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This paper reviews the literature on recent research on the chemical composition and pharmacological activities of saffron (Crocus sativus) and its active constituents, mainly as antitumoral, hypolipidemic and tissue oxygenation enhancement agents.
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Research into the chemical composition of saffron, the dried stigmas of Crocus sativus, has seen a renaissance in recent years. Different HPLC protocols for the analysis of saffron constituents have been established, enabling rapid authenticity control of the spice. Saffron flavor has attracted the interest of several research groups. Among the estimated 150 volatile compounds of saffron, approximately 40–50 constituents have so far been identified. Sensory studies allowed the detection of novel key flavor compounds. For some volatiles, generation from acid-labile progenitors was shown. Most recently, a considerable number of non-volatile aroma precursors could be isolated and structurally characterized. This paper reviews the present knowledge about the chemical composition of the world's most expensive spice and gives special emphasis to recent findings on saffron aroma formation.
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The acute effects of crocin and picrocrocin, major components of Crocus Sativus L., on learning and memory performances were investigated using mice in passive avoidance tasks. A single oral administration of crocin had no effect on memory acquisition in normal mice. Oral administration of 30% ethanol (10ml/kg) induced impairment of memory acquisition in step through and step down tests. Oral pre-administration of crocin (50 to 200mg/kg) improved the impairment of memory acquisition in both tests in a dose-dependent manner. Crocin (50 to 200mg/kg) also had beneficial effect on 40% ethanol (10mg/kg, p.o.)-induced memory retrieval deficit in step down test. Picrocrocin, the most abundant component in Crocus Sativus L., did not affect the impairment of memory acquisition and retrieval in step through and step down tests at 50-200mg/kg. These results suggest that crocin has preventive effect on the ethanol-induced impairment of learning and memory.
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Four new compounds, crocusatins F (1), G (2), H (3), and I (4a), together. with 21 known compounds, were isolated from an aqueous extract of the stigmas of Crocus sativus (saffron). The structures of I-A were established by spectral methods. The tyrosinase inhibitory activities of all 25 compounds isolated were evaluated in vitro using mushroom tyrosinase. Among them, crocusatin H (3), crocin l (5); and crocin-3 (6) showed significant tyrosinase inhibitory activity.
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The effect of an ethanol extract of Crocus sativus L. (CSE) on the long-term potentiation (LTP) of the evoked potential in the dentate gyrus of the hippocampus was investigated using anaesthetized rats. CSE (250 mg/kg, p.o.) alone did not affect the generation of LTP by application of subthreshold or suprathreshold tetanic stimulation (20 or 30 pulses at 60 Hz). Oral administration of ethanol (10–30%, 10 mL/kg) blocked the LTP induced by tetanic stimulation of 30 pulses at 60 Hz, but the LTP-blocking effect of ethanol was significantly attenuated by pre-administration of CSE (125 and 250 mg/kg, p.o.). The blockade of LTP induction by intravenously injected ethanol (30%, 2 mL/kg) was also antagonized by administration of CSE at doses of 125 and 250 mg/kg (p.o.). Oral administration of CSE antagonized also the LTP-blocking effect of ethanol directly injected into the brain, although it required a higher dose (500 mg/kg, p.o.). These results suggest that oral administration of CSE exerts an antagonistic effect on ethanol-induced impairment of hippocampal synaptic plasticity, which is possibly mediated by both direct action on the central nervous system and peripheral action.
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Extract of saffron (Crocus sativis) has previously been shown to inhibit colony formation and cellular DNA and RNA synthesis by HeLa cells in vitro. In order to compare the sensitivity of malignant and non-malignant cells to saffron, we examined the effect of the extract on macromolecular synthesis in three human cell lines: A549 cells (derived from a lung tumor), WI-38 cells (normal lung fibroblasts) and VA-13 cells (WI-38 cells transformed in vitro by SV40 tumor virus). We found that the malignant cells were more sensitive than the normal cells to the inhibitory effects of saffron on both DNA and RNA synthesis. There was no effect on protein synthesis in any of the cells.