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Effects of Saffron and its Active Constituents, Crocin and Safranal, on Prevention of Indomethacin Induced Gastric Ulcers in Diabetic and Nondiabetic Rats

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Background: Saffron is the dried stigmata of the flowers of saffron (Crocus sativus L., Iridaceae). Saffron is well known for the treatment of gastric disorders in traditional medicine. Objectives: In the search for new potential antiulcer agents, the effects of the ethanol extract of saffron and its active constituents crocin and safranal as compared with omeprazole against gastric ulcer induced by indomethacin in non-diabetic and streptozocin diabetic rats were studied. Methods: The effects of pretreatment with saffron extract ( 25, 100 or 250 mg/kg, p.o.) , crocin ( 2.5, 5 or 10 mg/kg, p.o.) and safranal ( 0.25, 2, 5 ml/kg, p.o.) and omeprazole (30 mg/kg, p.o.) 30 min before administration of indomethacin (40 mg/kg, p.o. in non-diabetic rats and 15 mg/kg, p.o. in diabetic rats) on gastric lesions, increase of lipid peroxidation and decrease of glutathione levels induced by indomethacin in non-diabetic and diabetic rats were evaluated. Results: Saffron extract, crocin, safranal and omeprazol prevented the gastric lesions, increase of lipid peroxidation and decrease of glutathione levels induced by indomethacin in non-diabetic and diabetic rats as compared with the control group (P < 0.01). The effects of saffron extract, crocin and safranal on the gastric ulcer index, lipid peroxidation and glutathione levels were comparable to omeprazole. Conclusions: Saffron, crocin and safranal may prevent the gastric mucosa damage due to their antioxidant properties by increasing the gluthatione levels and diminishing the lipid peroxidation in the rat gastric mucosa.
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Volume 8, Supplement No. 5, Winter 2009
Journal of Medicinal Plants
Effects of Saffron and its Active Constituents, Crocin and Safranal, on
Prevention of Indomethacin Induced Gastric Ulcers in Diabetic and
Nondiabetic Rats
Kianbakht S (Ph.D.)1*, Mozaffari K (M.D.)2
1- Department of Pharmacology and Applied Medicine, Institute of Medicinal
Plants, ACECR, Karaj, Iran
2- Department of Pathology, Faculty of Medicine, Iran University of Medical
Sciences, Tehran, Iran
*Correspondence author: Institute of Medicinal Plants, Complex of Academic
Center for Educational and Cultural Research (ACECR), Kavosh Boulevard, Supa
Boulevard, 55th Kilometer of Tehran-Gazvin Freeway, Pouleh Kordan, Karaj, Iran
Tel: +98-261-4764010-19, Fax: +98-261-4764021
E -mail: skianbakht@yahoo.com
Received: 14 Mar. 2009 Accepted: 20 Jun. 2009
Abstract
Background: Saffron is the dried stigmata of the flowers of saffron (Crocus sativus L.,
Iridaceae). Saffron is well known for the treatment of gastric disorders in traditional
medicine.
Objectives: In the search for new potential antiulcer agents, the effects of the ethanol
extract of saffron and its active constituents crocin and safranal as compared with
omeprazole against gastric ulcer induced by indomethacin in non-diabetic and
streptozocin diabetic rats were studied.
Methods: The effects of pretreatment with saffron extract (25, 100 or 250 mg/kg, p.o.),
crocin (2.5, 5 or 10 mg/kg, p.o.) and safranal (0.25, 2, 5 ml/kg, p.o.) and omeprazole (30
mg/kg, p.o.) 30 min before administration of indomethacin (40 mg/kg, p.o. in non-diabetic
rats and 15 mg/kg, p.o. in diabetic rats) on gastric lesions, increase of lipid peroxidation
and decrease of glutathione levels induced by indomethacin in non-diabetic and diabetic
rats were evaluated.
Results: Saffron extract, crocin, safranal and omeprazol prevented the gastric lesions,
increase of lipid peroxidation and decrease of glutathione levels induced by indomethacin
in non-diabetic and diabetic rats as compared with the control group (P < 0.01). The
effects of saffron extract, crocin and safranal on the gastric ulcer index, lipid
peroxidation and glutathione levels were comparable to omeprazole.
Conclusions: Saffron, crocin and safranal may prevent the gastric mucosa damage due
to their antioxidant properties by increasing the gluthatione levels and diminishing the
lipid peroxidation in the rat gastric mucosa.
Keywords: Saffron, Crocin, Safranal, Gastric ulcers, Diabetes mellitus, Rat
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Effects of Saffron
Introduction
Saffron is the dried stigmata of the flowers
of saffron (Crocus sativus L., Iridaceae) and is
cultivated widely in Iran, Spain, France, Italy,
Greece, Turkey, India and China. In addition
to being a widely used food additive, saffron is
used in the traditional medicine as a eupeptic,
diaphoretic, expectorant, tranquilizer,
aphrodisiac, emmenagogue, abortifacient and
in the treatment of hepatic disorders,
flatulence, vomiting, spasm, dental and
gingival pain, insomnia, depression, cognitive
disorders, seizures, lumbago, cough, asthma,
bronchitis, fever, colds, cardiovascular
disorders and cancer. Saffron is recognized as
an adaptogen in Indian ayurvedic medicine [1,
2]. Crocin, crocetin and safranal are the major
active constituents of saffron [3]. Previous
studies have demonstrated various
pharmacological effects of saffron and its
active constituents including anti-oxidant [4, 5,
6], anti-tumor [7], anti-genotoxic [8], memory
and learning enhancing [9], neuroprotective
[10], analgesic and anti-inflammatory [11],
anti - convulsant [12], antianxiety [13],
aphrodisiac [14], antidepressant [15],
antihypertensive [16], hypolipidemic [17],
insulin resistance reducing [18], tissues
oxygenation enhancing [19], bronchodilator
[20], antitussive [21], retina protective [22]
and immunostimulant [23] effects.
Besides being used as analgesics, the non-
steroidal anti-inflammatory drugs (NSAIDs)
are being increasingly used for prevention of
malignancies, stroke, pre-eclampsia,
Alzheimer's disease and many other illnesses
[24, 25]. However, the NSAIDs produce
gastroduodenal ulcers in 25% of the users,
often with bleeding and/or perforation.
Amongst the various factors known to cause
gastric ulcer, use of NSAIDs is the foremost
[26]. Gastric mucosa of diabetic rats is more
vulnerable to ulcerogens such as NSAIDs and
peptic ulcers in diabetic patients are more
severe and often associated with complications
such as gastrointestinal bleeding [27, 28].
Adequate remedy for the NSAID-induced
gastropathy has so far been elusive, despite
recent advances [29]. Further the existing
synthetic anti-ulcer drugs confer mild to severe
side effects. Thus there is a need for more
effective and safe anti-ulcer drugs. Plants are
the most important source for the new drug
development due to the resurgence of the
interest in the use of herbal preparations. Some
of the anti-ulcer drugs are known to exert their
action via anti-oxidative activity [30]. Thus in
view of the significant antioxidant effects of
saffron and its active constituents, crocin and
safranal, our aim of the present study was to
assess the possible anti-ulcerogenic activity of
saffron, crocin and safranal against
indomethacin induced acute gastric ulceration
in non-diabetic and streptozocin diabetic rats
by measuring gastric ulcer index and to
elucidate the role of antioxidant effects of
saffron, crocin and safranal in their anti-
ulcerogenic activity, gastric mucosa lipid
peroxidation and reduced glutathione (GSH)
levels were also measured.
Materials and methods
Plant material
The stigmas of Crocus sativus were
collected from the lands of Ghaen in the
province of southern Khorasan in December
and dried in shadow followed by grinding. The
identity of Crocus sativus was authenticated
by a botanist and a voucher specimen of the
plant (number 9723) was deposited in the
Tehran University Central Herbarium.
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Journal of Medicinal Plans, Volume 8,
Supplement No. 5, Winter 2009
Kianbakht & Author
Preparation of plant extract
The stigmas were extracted with ethanol
(80% V/V) by maceration for three days, and
then the mixture was centrifuged. The crude
extract was evaporated to dryness under
reduced pressure at 40 °C.
Drugs
Crocin, indomethacin and omeprazole
were purchased from Sigma, safranal from
Fluka and streptozocin from Upjohn &
Pharmacia. For dilution, all drugs and the
extract were dissolved in physiological saline.
All drugs were prepared immediately before
use.
Animals
Male adult Wistar rats (225 ± 25 g) from
our own breeding colony were used. Animals
were maintained under standard environmental
conditions and had free access to standard
rodent feed and water.
Induction of diabetes
Animals were given streptozocin in a
single intraperitoneal injection at a dose of
50 mg/kg. Five weeks after the injection of
streptozocin, diabetic rats with fasting blood
glucose levels more than 350 mg/dl were used
for testing the anti-ulcer activity of the drugs.
Anti-ulcer activity
Rats were deprived of food for 48 h prior
to starting the experiments but they had free
access to drinking water. The animals were
kept in cages with raised floors of wide mesh
to prevent coprophagia and they were divided
into groups of 10 diabetic or non-diabetic rats
each. Gastric ulceration was induced by the
administration of indomethacin suspended in
0.5% carboxymethylcellulose (CMC) in water
(40 mg/kg, p.o. in non-diabetic rats and 15
mg/kg, p.o. in diabetic rats) as the ulcerogenic
agent. Each group of animals was pretreated
with physiological saline as control, saffron
stigmas extract (25, 100 or 250 mg/kg, p.o.),
crocin (2.5, 5 or 10 mg/kg, p.o.), safranal
(0.25, 2, 5 ml/kg, p.o.) or omeprazole (30
mg/kg, p.o.) 30 min before the indomethacin
administration. All drugs and the extract were
dissolved and administered in physiological
saline in a volume of 5 ml/kg.
The animals were killed 6 h after the
indomethacin administration by using an
overdose of chloroform. The stomachs were
removed, opened along the greater curvature
and washed in physiological saline. A person
unaware of the type of treatment received by
the animals, examined the stomachs under a 3-
fold magnifier and scored the lesions as
follows: 0, no pathology; 1, each pinhead ulcer
spot; and 2-5, thread-like lesions of 2-5 mm
length. The total number of ulcer spots divided
by the number of animals gives the ulcer index
[30].
Measurement of lipid peroxidation
The levels of thiobarbituric acid reactants
(TBARS) in the gastric mucosa as index of
lipoperoxides production were measured
according to the modified method of Okawa et
al. (1979) [31]. The mucosa was scraped with
glass slides, weighed, and homogenized in 10
mL KCl (10 %). The homogenate was
supplemented with 8.1 % sodium lauryl
sulfate, 20 % acetic acid, and 0.8 % TBA, and
boiled at 100 °C for 1h. After cooling, the
reactants were supplemented with 2.5 mL n-
butanol, shaken vigorously for 1 min, and
centrifuged for 10 min at 2600 × g.
Absorbance was measured in a spectro-
photometer Perkin-Elmer Lambda 3 at 532
nm, and the results were expressed as nmol of
malondialdehyde (MDA)/g tissue.
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Effects of Saffron
Measurement of gastric mucosa GSH level
Glutathione (GSH) content (as acid-soluble
sulfhydryl) of gastric mucosa was determined
as described earlier [30]. Gastric mucosa was
homogenized in 10 mL of 20 mM ice-cold
EDTA for 40 s and centrifuged at 2000g for 10
min. Protein was precipitated with equal
volume of 10% trichloroacetic acid. The
supernatant (2 mL) was added to 2 mL of 0.8
M Tris-Cl, pH 9, containing 20 mM EDTA
and mixed with 0.1 mL of 10 mM DTNB
(5,5'–dithio-bis (2-nitro-benzoic acid) to yield
thionitrobenzoic acid, which was measured at
412 nm using GSH as standard. The result was
expressed as nmol of GSH/g of tissue.
Statistical analysis
The results were expressed as means ± S.D.
and analyzed with the independent samples t
test. p < 0.05 was regarded as significant.
Results
Omeprazole, saffron, crocin and safranal
decreased the gastric ulcer index and lipid
peroxidation but increased the gastric tissue
glutathione levels at the doses used
significantly as compared to the saline +
indomethacin group in non-diabetic and
diabetic rats (p < 0.01) (Tables 1 and 2).
Table 1: Effects of pretreatment with omeprazole, saffron extract, crocin and safranal on gastric ulcer index,
gastric mucosa lipid peroxidation and GSH level in non-diabetic rats treated with indomethacin (40 mg/kg, p.o.).
* p < 0.01 vs. saline + indomethacin. ** p < 0.01 vs. saline + saline.
Treatment
(N = 10 in each group) Dose (p.o.) Ulcer index Lipid peroxidation
(nmol MDA/g tissue)
GSH (nmol/g
tissue)
Saline + saline - - 110.8 ± 20.4 197.1 ± 13.6
Saline + indomethacin - 37.3 ± 5.6 217.2±23.8** 132.3±6.8**
Omeprazole 30 mg/kg 15.2 ± 7.1 * 96.6 ± 20.1* 182.1±15.7 *
Saffron 25 mg/kg 23.1 ± 2.8 * 143.1± 12.4* 157.5±4.5 *
Saffron 100 mg/kg 14.2 ± 5.1 * 112.9± 10.2* 179.3±11.7 *
Saffron 250 mg/kg 11.3 ± 3.3 * 123.2± 18.7* 162.8±16.2 *
Crocin 2.5 mg/kg 19.5 ± 4.9 * 129.1± 14.3* 178.3±5.6 *
Crocin 5 mg/kg 10.6 ±2.8 * 92.1± 17.2* 201.9±12.2 *
Crocin 10 mg/kg 12.3 ± 3.4 * 89.6± 14.5* 192.3±8.6 *
Safranal 0.25 ml/kg 24.8 ± 3.8 * 118.6± 9.8* 162.7±17.3 *
safranal 2 ml/kg 13.2 ± 4.5 * 93.1± 11.6* 218.9±9.2 *
Safranal 5 ml/kg 11.2 ± 2.6 * 87.4± 12.8* 197.6± 14.4*
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Journal of Medicinal Plans, Volume 8,
Supplement No. 5, Winter 2009
Kianbakht & Author
Table 2- Effects of pretreatment with omeprazole, saffron extract, crocin and safranal on gastric ulcer index,
gastric mucosa lipid peroxidation and GSH level in diabetic rats treated with indomethacin (15 mg/kg, p.o.).
* p < 0.01 vs. saline + indomethacin. **p < 0.01 vs. saline + saline.
Treatment
(N = 10 in each
group)
Dose (p.o.) Ulcer index Lipid peroxidation
(nmol MDA/g tissue)
GSH (nmol/g
tissue)
Saline + saline - - 101.8 ± 15.6 224.8 ± 16.8
Saline + indomethacin - 42.6 ± 6.7 197.2±27.1** 111.3±15.6**
Omeprazole 30 mg/kg 23.7 ± 6.2 * 82.7 ± 12.5* 189.1 ± 8.6*
Saffron 25 mg/kg 27.8 ± 7 * 111.7± 10.1* 148.4 ± 9.4*
Saffron 100 mg/kg 14.7 ± 3.7 * 88.9 ± 5.7* 165.2 ± 5.4*
Saffron 250 mg/kg 10.3 ± 6.2 * 74.3 ± 9.8* 178.5± 15.6*
Crocin 2.5 mg/kg 27.5 ± 5.1 * 101.7± 10.3* 172.1 ± 8.2*
Crocin 5 mg/kg 17.4 ± 2.8 * 74.2 ± 13.6* 201.3 ± 13.2*
Crocin 10 mg/kg 14.2 ± 4 * 65.6 ± 17.5* 192.4 ± 8.1*
Safranal 0.25 ml/kg 26.6 ± 5.2 * 89.6 ± 8.3* 168.2± 12.8*
safranal 2 ml/kg 16.7 ± 3.1 * 72.1 ± 6.6* 211.5 ± 9.7*
Safranal 5 ml/kg 12.1 ± 3.8 * 62.4 ± 7.8* 197.1± 15.1*
Discussion
The main findings of this study are as
follows: (1) indomethacin has caused gastric
lesions in diabetic rats at a dose (15 mg/kg,
p.o.), less than half the dose used in non-
diabetic rats (40 mg/kg, p.o.), in addition to
increasing lipid peroxidation and decreasing
glutathione levels in the gastic mucosa, (2)
There is no significant differences between the
ulcer indexes, lipid peroxidation and
glutathione levels induced by indomethacin at
the dose of 40 mg/kg and the dose of 15 mg/kg
in the non-diabetic rats and diabetic rats, (3)
Omeprazole (30 mg/kg, p.o.) has prevented the
gastric lesions, increase of lipid peroxidation
and decrease of glutathione levels induced by
indomethacin in non-diabetic and diabetic rats
as compared with the control group (p < 0.01),
(4) Saffron extract, crocin and safranal have
prevented dose dependently the gastric lesions,
increase of lipid peroxidation and decrease of
glutathione levels induced by indomethacin in
non-diabetic and diabetic rats as compared
with the control group (p < 0.01), (5) The
effects of saffron extract, crocin and safranal
on the gastric ulcer index, lipid peroxidation
and glutathione levels are comparable to
omeprazole (Tables 1 and 2).
The lower dose of indomethacin needed to
induce gastric lesions in diabetic rats as
compared to non-diabetic rats is in line with
the fact that gastric mucosa of diabetic rats is
more vulnerable to ulcerogenic agents [27,
28].
The results conform to a variety of studies
in which saffron, crocin and safranal had
protective effects against oxidation induced
tissue injuries due to their antioxidant
properties. Crocin prevented the death of the
neuronally differentiated pheochromocytoma
(PC-12) cells deprived of serum/glucose more
effectively than α-tocopherol by inhibiting the
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Effects of Saffron
formation of peroxidized lipids [32]. Crocin
suppressed serum-deprivation induced death of
PC-12 cells by increasing glutathione
synthesis and inhibition of membrane lipids
peroxidation [33]. Saffron, crocin and safranal
had protective effects against lower limb
skeletal muscle injury during ischemia-
reperfusion by elevating total sulfhydryl
contents, antioxidant capacity and decreasing
malondialdehyde [34]. Safranal protected
against neuronal cell death in the rat
hippocampus following cerebral ischemic
injury by elevating total sulfhydrl
concentrations and antioxidant capacity and
diminishing malondialdehyde in the
hippocampus [35]. Crocin protected the rat
brain against excessive oxidative damage in
transient global cerebral ischemia by
decreasing malondialdehyde levels and
elevating gluthatione peroxidase activity [36].
Saffron had protective effects against
genotoxins induced oxidative stress by
increasing glutathione levels and reducing
lipid peroxidation in mice [37].
Indomethacin induced gastric ulcer is a
multifactorial process where reactive oxygen
species (ROS) play a vital role in gastric
damage either by its direct oxidative action or
through apoptotic cell death. Among various
ROS, H202 can act as a signal transduction
messenger to activate transcription factors
NFκB (Nuclear Factor Kappa B) and AP-1
(Activator Protein 1) for gene expression of
various inflammatory cytokines and proteases
to cause cell damage. In fact, involvement of
TNF-α (Tumor Necrosis Factor Alpha) and
matrix metalloproteinases has been evident in
indomethacin-induced gastric hypermotility
and increased microvascular injury also cause
ischemia to generate ROS through the
mitochondrial electron transport chain.
Mitochondria from gastric mucosal cells
contain a highly active peroxidase to scavenge
H202 and protect the cells from ROS-mediated
oxidative damage. Indomethacin significantly
inactivates the gastric peroxidase to generate
H202 and H202–derived ˙OH. Thus
indomethacin significantly increases
endogenous ˙OH to cause oxidative damage by
increased lipid peroxidation and thiol
depletion [38].
In this study, omeprazole has prevented
gastric lesions, increase of lipid peroxidation
and decrease of glutathione level as compared
to control (p < 0.01) which is in line with the
previous studies [39, 40]. The fact that proton
pump inhibitors such as omeprazole have
pronounced antioxidant properties and
scavenge hydroxyl radicals may explain the
observed effects of omeprazole [41, 42].
In conclusion, the results of the present
study suggest that saffron, crocin and safranal
may prevent the indomethacin-induced gastric
mucosa damage due to their antioxidant
properties by increasing the gluthatione levels
and diminishing the lipid peroxidation in the
rat gastric mucosa. Thus further investigations
concerning efficacy and safety of saffron and
its active constituents in prevention of NSAID-
induced gastric ulcers in humans seem to be
warranted.
Acknowledgements
We are grateful to the Pharmaceutical
Research Network affiliated with the Research
Deputy of the Iranian Ministry of Health and
Medical Education for sponsoring this study.
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Journal of Medicinal Plans, Volume 8,
Supplement No. 5, Winter 2009
Kianbakht & Author
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... Analysis of hyperspectral data using machine learning algorithms to classify healthy and diseased saffron plants based on spectral signatures was emphasized. Kianbakht, S et al. (2010) [48] explored the application of computer vision and deep learning techniques for saffron disease detection. They discussed the use of Convolutional Neural Networks (CNNs) to extract discriminative features from saffron plant images and classify them as healthy or diseased. ...
Article
Saffron, derived from the dried stigmas of the Crocus sativus plant, holds immense value as an agricultural product. With a rich history spanning over 3500 years, saffron has been revered as a precious spice and has gained popularity due to its medicinal properties and diverse applications. As the demand for saffron continues to rise, efforts to increase productivity and expand cultivation face various challenges. One significant hindrance is the prevalence of diseases affecting saffron plants, which not only reduce yields but also impact the quality of saffron stigmas. This review paper offers a thorough and inclusive exploration of saffron-related diseases. Encompassing their historical backdrop, present conditions, impact on yield, dynamics of pathogens, methods of survival and spread, variables affecting disease severity, epidemiology, and approaches for sustainable management. Through the investigation of diseases and their discernment using machine learning techniques, the intention of this review is to be of advantage to cultivators, students, scholars, plant protection entities, developmental divisions, outreach staff, policymakers, governmental bodies, and civic organizations. Overall, this review sheds light on the significance of saffron diseases, their impact on production, and the importance of adopting effective disease management strategies. By disseminating this knowledge, stakeholders can make informed decisions to mitigate the risks associated with saffron diseases and contribute to the sustainable growth of the saffron industry.
... Previous studies indicated that crocin treatment after STZ administration of rats ameliorated remarkably the elevated levels of GSH, as well as the decrease of lipid profiles and oxidative stress parameters, MDA, compared with untreated diabetic rats in plasma and heart tissue. These results were supported by other researchers using saffron and crocin, which recovered from oxidative damage via diabetes in rats (Plants and Karaj, 2009). We observed that these results are confirmed by variety of researches in which saffron, crocin, crocetin and safranal have protective effects against oxidative damage in the STZ diabetic rats by scavenging free radicalls . ...
Article
Background: Diabetes mellitus (DM) causes serious complications such as coronary heart disease, atherosclerosis, nephropathy, retinopathy and neuropathy. Materials and Methods: Rats were randomly divided into three groups each containing 10 rats; control group, DM group; DM+crocin group. Normal saline was administered in the control and DM groups, and crocin was administered in DM+crocin group at a dose of 20 mg/kg bw/day for 21 days. Trunk blood and the hearth tissue were collected for histopathological and biochemical examination. Results: DM led to increment of MDA levels (p
... However, tepals and stamen are simply discarded while just flower stigmas are utilized to make saffron [1]. It is cultivated in Iran, Morocco, Greece, Azerbaijan, Pakistan, Italy, and Spain, which are the largest producers of saffron [2]. One of the oldest, most precious, and most expensive spices is saffron. ...
Article
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Saffron spices are composed of dehydrated stigmas of Crocus sativus L. A large amount of bio-residues (stamens, tepals, and stigmas) is generated during the production of this spice (~92 g of bio-residues per 100 g of flowers). These bio-residues are usually discarded losing the chance to obtain interesting bioactive compounds from them. In this work, we use the saffron bio-residues as possible source of natural bioactive compounds. Different extraction conditions were applied obtaining hydrophilic and lipophilic components. The antioxidant activity of the bioactive compounds in the different conditions were analysed using the ABTS method developed by our team. Furthermore, the total content of phenolic compounds and flavonoids present in the bio-residues were estimated. We demonstrated that bio-residues contain a high amount of both phenolic and flavonoid compounds with a strong antioxidant potential effect. Moreover, we compared the antioxidant activities of saffron bio-residues (obtained from stamens, tepals, and stigmas). The extraction was made at two different pH (4.5 and 7.5) and measured (antioxidant activity, flavonoid and phenol content) at pH 7.5. Another extraction done at pH 7.5 measured antioxidant activity, flavonoid and phenol content at time 0 (t = 0 h) and after 24 h (t = 24 h) at pH 4.5 and 7.5. We point out that bioresidues contain antioxidant activity (up to 8.42 µmoles Trolox/100 g DW), total phenols (up to 111.91 µmoles EG/100 g DW) and total flavonoids (up to 109.25 µmoles QE/100 g DW) as bioactive compounds. The applicability of bio-residues as additives is promising, both in the pharmaceutical and in the food industry as nutraceuticals and phytogenics. The variability in pH and the colour originating from it must be taken into account.
... Aside from its main use as a spice, saffron exhibits significant biological activity. Several scientific studies have reported that saffron and its chemical components are potential anti-ulcer agents [9], they improve digestion [10], they play a role as anti-cancerogenic [11], they reduce atherosclerosis [12,13,14], and they used as anti-depressant in the traditional medicine [15]. "Additionally, saffron presents interesting results in the prevention and maintenance of cancer due to its antioxidant properties" [16]. ...
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Saffron is the most expensive spice in the world, it is highly valued as a culinary spice for its flavor and color properties. Since saffron is an expensive product, it is cheated by the dealers, therefore, quality control of saffron is important for the spice industries and also the consumers. This study aims to evaluate the saffron quality in Omani markets according to the ISO standard. A total of 21 saffron samples were examined; 2 in powder form and 19 in filaments. The samples of saffron were purchased from different hyper-markets and local markets in Muscat, Oman. Saffron’s commercial value is determined according to the ISO standard which include moisture, ash, acid insoluble ash, extract %, sulfuric test, artificial colors, spectrum, Flavor, aroma and color. The saffron samples were in line with standard in terms of moisture, ash, acid insoluble ash and extract %. The two powder saffron samples failed in sulfuric, spectrum and flavor tests. From the 19 samples of saffron filament, three samples were failed to achieve the flavor and color limits required by the standard. This failure to standard quality could be due to poor processing condition such as drying and packaging or due to adulteration. The standard parameters could not distinguish between low quality and adulteration due to its limited and unspecific parameters. Therefore, we recommend improving the saffron standard with parameters targeting adulteration.
... Starting from its antioxidant action, other effects have emerged, such as anti-cancer, anti-toxic [28][29][30], anti-nociceptive [31,32] and anti-inflammatory ones [32][33][34]. Saffron promotes a decrease in blood glucose levels and an increase in insulin secretion by pancreatic β-cells; therefore, it appears to be endowed with anti-diabetic and hypoglycemic effects [35][36][37]. In addition, crocin and safranal are believed to exert antidepressant effects [38,39], since crocin may inhibit dopamine and norepinephrine uptake, while safranal can affect the serotonergic system. ...
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Dyslipidemia is a lipid metabolism disorder associated with the loss of the physiological homeostasis that ensures safe levels of lipids in the organism. This metabolic disorder can trigger pathological conditions such as atherosclerosis and cardiovascular diseases. In this regard, statins currently represent the main pharmacological therapy, but their contraindications and side effects limit their use. This is stimulating the search for new therapeutic strategies. In this work, we investigated in HepG2 cells the hypolipidemic potential of a picrocrocin-enriched fraction, analyzed by high-resolution 1 H NMR and obtained from a saffron extract, the stigmas of Crocus sativus L., a precious spice that has already displayed interesting biological properties. Spectrophotometric assays, as well as expression level of the main enzymes involved in lipid metabolism, have highlighted the interesting hypolipidemic effects of this natural compound; they seem to be exerted through a non-statin-like mechanism. Overall, this work provides new insights into the metabolic effects of picrocrocin, thus confirming the biological potential of saffron and paving the way for in vivo studies that could validate this spice or its phytocomplexes as useful adjuvants in balancing blood lipid homeostasis.
... Safranal, a monoterpene aldehyde isolated from saffron (Crocus sativus), has shown radical-scavenging and anti-apoptotic properties [83], and conferred protection against indomethacininduced gastric ulcers [84], pentylenetetrazolinduced status epilepticus [85], and cancer [86]. Safranal also showed an anti-ischemic effect during renal IRI [87]. ...
Article
The PI3K/Akt/GSK3β pathway is crucial in regulating cardiomyocyte growth and survival. It has been shown that activation of this pathway alleviates the negative impact of ischemia-reperfusion. Glycogen synthase kinase-3 (GSK3β) induces apoptosis through stimulation of transcription factors, and its phosphorylation has been suggested as a new therapeutic target for myocardial ischemia-reperfusion injury (MIRI). GSK3β regulatory role is mediated by the reperfusion injury salvage kinase (RISK) pathway, and its inhibition by Akt activation blocks mitochondrial permeability transition pore (mPTP) opening and enhances myocardial survival. The present article discusses the involvement of the PI3K/Akt/GSK3β pathway in cardioprotective effects of natural products against MIRI.
... b Within-group mean difference (95% CI) based on paired t-test. account for increased glutathione levels and decreased lipid oxidation and MDA(Kianbakht & Mozaffari, 2009).Hazman et al., reported that saffron could alleviate inflammation and oxidative stress in serum as well as in the pancreas(Hazman & Ovalı, 2015). Despite these experimental findings, there is limited evidence regarding the antioxidant properties of saffron in humans. ...
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In the current study, we aimed to investigate the effect of saffron supplementation on glycemic status, lipid profile, atherogenic indices, and oxidative status in patients with type‐2 diabetes (T2DM). In a randomized, double‐blind controlled trial, 70 patients were randomly allocated into two groups (n = 35, each) and received 100 mg/day of saffron or placebo for eight weeks. Dietary intake, weight, body mass index (BMI), waist and hip circumferences (WC and HC), waist to hip ratio (WHR), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, and Homeostatic model assessment for insulin resistance (HOMA‐IR), lipid profile, atherogenic indices, oxidative status, and liver enzymes were determined before and after the intervention. At the end of the eighth week, saffron intervention could significantly reduce FBS (7.57%), lipid profile (except high‐density lipoprotein cholesterol [HDL‐C]), atherogenic indices, and liver enzymes (p < .05). Moreover, saffron could improve oxidative status (nitric oxide [NO] and malondialdehyde [MDA] reduced by 26.29% and 16.35%, respectively). Catalase (CAT) concentration remained unchanged. Saffron supplementation may alleviate T2DM by improving glycemic status, lipid profile, liver enzymes, and oxidative status. Further investigation is necessary to assess possible side effects and confirm the positive effect of saffron as a complementary therapy in clinical recommendations for T2DM.
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Cistus albidus L. (Cistaceae) is a medicinal plant that has been used therapeutically since ancient times in the Mediterranean basin for its important pharmacological properties. The ability of C. albidus to produce large quantities of a wide range of natural metabolites makes it an attractive source of raw material. The main constituents with bioactive functions that exert pharmacological effects are terpenes and polyphenols, with more than 200 identified compounds. The purpose of this review is to offer a detailed account of the botanical, ethnological, phytochemical, and pharmacological characteristics of C. albidus with the aim of encouraging additional pharmaceutical investigations into the potential therapeutic benefits of this medicinal plant. This review was carried out using organized searches of the available literature up to July 2023. A detailed analysis of C. albidus confirms its traditional use as a medicinal plant. The outcome of several studies suggests a deeper involvement of certain polyphenols and terpenes in multiple mechanisms such as inflammation and pain, with a potential application focus on neurodegenerative diseases and disorders. Other diseases such as prostate cancer and leukemia have already been researched with promising results for this plant, for which no intoxication has been reported in humans.
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Essential oil, obtained from the stem of Dombeya buettneri and characterized by high resolution GC–MS was tested for antimicrobial (using broth dilution method) and antioxidant (using spectrophotometric methods: DPPH, FRAP and ABTS) properties.Forty-three (43) essential oil components were detected which account for 96.8% of the total oil content comprising mainly: Non-terpene derivatives (31.8%), Apocarotenes (24.3%), Sesquiterpenoids (15.3%), Sesquiterpene hydrocarbons (14.4%), Monoterpenoids (10.1%) and Monoterpene hydrocarbons (0.9%). The major identified compounds in the oil were (E)-geranylacetone (14.8%), δ-cadinene (8.9%), n-hexadecane (7.8%), Tetradecanal (6.2%), β-ionone (4.9%), Borneol (4.2%), Viridiflorol (3.5%), Guaiol (3.4%), caryophyllene oxide (3.4%), Palustrol (2.5%) and Spathulenol (2.5%).The oil displayed antibacterial and antifungal activities on Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Candida albicans ATCC 18804 with respective Minimum Inhibitory Concentration (MIC) of 6.25, 12.5 and 12.5%v/v. The Minimum Bactericidal/Fungicidal Concentrations on the test organisms ranged from 12.5 to 25.0%v/v. The antioxidant assay by DPPH showed a concentration dependent values of 8.0993±0.827 at 25 mg/mL, 14.7657±0.8151 and 19.449±0.6678 at 100 mg/mL with good IC50 value of 1098 µg/mL as compared with reference ascorbic acid standard with IC50 of 23.52 µg/mL. The Ferric reducing antioxidant assay (FRAP) showed activity at concentration of 0.076713±0.001227mg/FeSO4Equiv./g, while ABTS showed an activity at 0.3776±0.0025 mg AA Equiv./g with respect to the standards.The current study showed that the volatile oil of Dombeya buettneri stem possess good antioxidant and antimicrobial properties that could be utilized for cosmetic and pharmaceutical health benefits.
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Crocin plays a crucial role in curing of the disorders of the nervous and cardiac system. But the low stability and oral bioavailability limit its application. As an encapsulation material, casein (CN) has been widely used to protect the bioactive substances from degradation. This study investigated the formation mechanism of casein-crocin (Cro/CN) nanocomplexes and its effects on the stability and bioavailability of crocin. Results showed that Cro/CN nanocomplexes can effectively improve the storage, thermal and lighting stability of the crocin. The fluorescence spectrum showed that the binding of CN with crocin would result in static quenching and the binding forces were Van der Waals forces and hydrogen bonding. For the pharmacokinetic study, animals treated with Cro/CN nanocomplexes showed a significantly higher in serum crocin level than treated with the crocin solution. Eventually, the bioavailability of crocin in Cro/CN nanocomplexes was about five times more than that of the crocin solution.
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Saffron is the dried stigmata of the flowers of saffron (Crocus sativus L., Iridaceae). Saffron has various pharmacological effects and is regarded as a potent drug. Thus research on the biological activities of saffron and its active constituents may have clinical and public health applications. To evaluate the basic and clinical pharmacology of saffron and its active constituents, the English papers in the data bases EMBASE, SCOPUS, MEDLINE, SCIENCE DIRECT, CHEMICAL ABSTRACTS, English and Persian papers in the data base SID and proceedings of the Iranian physiology and pharmacology congresses and Iranian congresses concerning saffron were retrieved by using keywords comprising Crocus sativus, anti-tumor, anti-oxidant, anti-genotoxic, memory, neuroprotective, analgesic, anticonvulsant, opioid dependence, antidepressant, cardiovascular, lipids, respiratory, gastric ulcer, immune system, ocular, antimicrobial and toxicity and their Persian equivalents from 1975 until November 2008. The investigations demonstrate that saffron and its active constituents have anti-tumor, anti-oxidant, anti-genotoxic, memory and learning enhancing, neuroprotective, analgesic and anti-inflammatory, anticonvulsant, opioid abstinence syndrome alleviating, antidepressant, hypotensive, hypolipidemic, insulin resistance reducing, tissues oxygenation enhancing, bronchodilator, antitussive, gastric ulcer preventive, Immune-stimulator, retina protective and antibacterial effects. In view of the existing deficiencies in the conducted researches, further clinical trials, pharmacokinetic and toxicological studies concerning saffron are recommended.
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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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Saffron and its constituents have been shown to decrease ischemia-reperfusion (I/R) injury in kidney or brain tissues. In this study, the effects of saffron ethanolic extract and its constituents, crocin and safranal, were evaluated in skeletal muscle during I/R injury. Hind limb ischemia was induced using clamping the common femoral artery and vein. After 2 h ischemia, the clamp of the femoral vessels of animals was taken off and the animal underwent 1h reperfusion. Muscle injuries were evaluated by recording of the electromyographic (EMG) potentials and performing some biochemical analysis including thiobarbituric acid reactive substances (TBARS), total sulfhydryl (SH) groups and antioxidant capacity of muscle (using FRAP assay). The ethanolic extract of saffron (5, 20 and 80 mg kg(-1)), crocin (50, 200 and 400 mg kg(-1)), safranal (0.1, 0.25 and 0.5 ml kg(-1)) and normal saline (10 ml kg(-1)) were administered intraperitoneally 1 h prior reperfusion. The average peak-to-peak amplitude during I/R was significantly increased in extract, crocin and safranal groups in comparison with control-ischemic group. Following saffron, crocin and safranal administration, the total SH contents and antioxidant capacity were elevated in muscle flap. The MDA level was declined significantly in test groups. It is concluded that saffron extract and its constituents show a protective effect against lower limb I/R in rat.
Article
The recent advances in separation and characterization of the volatile and non-volatile components of the dried stigmas of Crocus sativus (saffron) are presented. The volatiles with a very strong odor are consistent of more than 34 components that are mainly terpenes, terpene alcohols and their esters. Non-volatiles include crocins 1,2,3 and 4 that are responsible for the red or reddish brown colorof stigmas together with carotenes, crocetin, picrocrocin (a glycosidic precursor of safranal) the bitter substance and safranal the majororganoleptic principle of the stigmas. The methodology and techniques developed for the analysis of saffron metabolites including various chromatographic and spectroscopic techniques (TLC, HPLC, GC-MS, LC-MS, NMR.) are described.An extended study of the biological effects of either extracts or specific constituents of saffron (crocetin, picrocrocin and safranal) or extracts from its roots, from experiments in vivo and in vitro are discussed. A growing body of evidence indicates that carotenoids possess anticarcinogenic, antimutagenic and immunomodulating effects. Othereffects such as lowering of blood pressure, stimulation of respiration, sedative effects, inhibition of human platelet aggregation in vitroand the dietary effects are reported as well. In addition the use of its coloring agents (crocins and carotenes) in dying cotton and wool fabrics and/or other uses in industry as well as attempts for biotechnological production of saffron and its metabolites are mentioned.
Article
Crocins are water-soluble carotenoids responsible for the colour of saffron and gardenia. In this study, we isolated and identified three major crocins from gardenia, and then evaluated their antioxidant potential using four in vitro antioxidant tests in comparison with saffron ethanol extract (SE), gardenia ethanol extract (GE) and gardenia resin fraction (GRF). The relationship between total crocin contents and antioxidant activity of ethanol extracts of two herbs was investigated and the antioxidant potentials of three different polar crocins were compared. The crocins appeared to possess antioxidant activity when tested by four in vitro antioxidant models. However, in anti-hemolysis, DPPH radical-scavenging and lipid peroxidation assays, GRF exhibited significantly stronger antioxidant activity than crocins and no correlation between total crocin contents and antioxidative function was revealed, which implied that ingredients other than crocins in gardenia gave markedly strong antioxidant activity. In the phosphomolybdenum assay, antioxidant capacities of fractions and extracts correlated with total crocin contents (R = 0.93). Moreover, comparison of results indicated that sugars attached to the crocetin moiety seemed to be beneficial for the antioxidant activity of these water-soluble pigments.
Article
Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.
Article
Crocus sativus L. is a plant cultivated in various parts of the world. Crocins are among the active components of Crocus sativus L. The present study was designed to investigate in the rat whether or not crocins possess anxiolytic properties. For this aim, the light/dark test was selected. Either crocins, at a dose which did not influence animals' motor activity (50mg/kg), or diazepam (1.5 mg/kg), significantly increased the latency to enter the dark compartment and prolonged the time spent in the lit chamber in the rats. Conversely, lower doses of crocins (15-30 mg/kg) did not substantially modify animals' behaviour. The present results indicate that treatment with these active constituents of Crocus sativus L. induce anxiolytic-like effects in the rat.