Printer Friendly

Stimulatory effect of Crocus sativus (saffron) on [[beta].sub.2]-adrenoceptors of guinea pig tracheal chains.

Abstract

To study the mechanism(s) of the relaxant effects of Crocus sativus (Iridaceae), the stimulatory effect of aqueous-ethanolic extracts of this plant and one of its constituent, safranal was examined on [beta]-adrenoceptors in tracheal chains of guinea pigs.

The [[beta].sub.2]-adrenergic stimulatory was tested by performing the cumulative concentration-response curves of isoprenaline-induced relaxation of pre-contracted isolated guinea pig tracheal chains. The studied solutions were included two concentrations of aqueous-ethanolic extract from Crocus sativus (0.1 and 0.2 g%), safranal (1.25 and 2.5 [micro]g), 10nm propranolol, and saline. The study was done in two different conditions including: non-incubated (group 1, n = 9) and incubated tissues with 1 [micro]M chlorpheniramine (group 2, n = 6).

The results showed clear leftward shifts in isoprenaline curves obtained in the presence of only higher concentration of the extract in group land its both concentrations in group 2 compared with that of saline. The E[C.sub.50] (the effective concentration of isoprenaline, causing 50% of maximum response) obtained in the presence of both concentrations of the extract (0.17 [+ or -] 0.06 and 0.12 [+ or -] 0.02) and safranal (0.22 [+ or -] 0.05 and 0.22 [+ or -] 0.05) in group 1 and only in the presence of two concentrations of the extract (1.16 [+ or -] 0.31 and 0.68 [+ or -] 0.21) in group 2 was significantly lower compared to saline (1.00 [+ or -] 0.22 and 4.06 [+ or -] 1.04 for groups 1 and 2, respectively) (p < 0.05-0.001). The maximum responses obtained in the presence of both concentrations of the extract and safranal in group 1 were significantly lower than that of saline (p < 0.005 for all cases). All values (CR-1 = ([EC.sub.50] obtained in the presence of active substances/[EC.sub.50], obtained in the presence of saline)-1) obtained in the presence of higher concentrations of extract in group 1, its both concentrations and higher concentration of safranal in group 2 were negative and there were significant differences in this value between propranolol and those obtained in the presence of extract and safranal (p < 0.05 to p < 0.001).

The results indicated a relatively potent stimulatory effect of the extract from Crocus sativus on [[beta].sub.2]-adrenoceptors which is partially due to its constituent, safranal. A possible inhibitory effect of the plant on histamine ([H.sub.1]) receptors was also suggested.

[C] 2008 Elsevier GmbH. All rights reserved.

Keywords: Crocus sativus: Iridaceae; Stimulatory effect; [[beta].sub.2]-Adrenoceptors; Guinea pig; Trachea

Introduction

Crocus sativus L, commonly known as saffron, is a small perennial plant from the iris family (Iridaecae) which is cultivated in many places, but particularly in Spain and Iran. It has green, hairy leaves about 1-1/2 ft long with a funnel-shaped, reddish-purple flower. The medicinally used part of the plant is its stigma, also called the style (central part of the flower, female sexual organ). The main constituents of this plant are crocins, safranal, picrocrocin, ketoisophorone, isophorone, glycosidic terpenoids (Trantilis et al., 1995).

In traditional medicine, Crocus sativus is used as an antispasmodic, eupeptic, gingival sedative, anticatarrhal, nerve sedative, carminative, diaphoretic, expectorant, stimulant, stomachic, aphrodisiac, and emmenagogue (Rios et al., 1996; Abdullaev and Espinosa-Aguirre, 2004).

Previous studies have shown different pharmacological effects for this plant including: anticonvulsant (Hosseinzadeh and Khosravan, 2002; Hosseinzadeh and Talebzadeh, 2005), antidepressant (Hosseinzadeh et al., 2004; Akhondzadeh et al., 2005, 2007), antiinflammatory (Hosseinzadeh and Younesi, 2002), radical scavenger and antioxidant properties (Abe et al., 1999; Verma and Bordia, 1998; Assimopoulou et al., 2005; Papandreou et al., 2006; Kanakis et al., 2007), and antitumour effects (Rios et al., 1996; Abdullaev and Espinosa-Aguirre, 2004; Abdullaev, 1993; Escribano et al., 1996; Abdullaev and Ferenkel, 1992; Das et al., 2004; Chryssanthi et al., 2007). It has been also reported that the plant has learning and memory improving properties (Zhang et al., 1994; Abe and Saito, 2000; Pitsikas and Sakellaridis, 2006). Saffron extract also has chemopreventive and genoprotective effects and protects from genotoxins-induced oxidative stress in mice (Abdullaev and Ferenkel, 1992; Nair et al., 1995; Premkumar et al., 2001, 2003, 2006). A lowering blood pressure effect (Rios et al., 1996) and relaxant effect on vascular (Fatehi et al., 2003), and tracheal smooth muscle (Boskabady and Aslani, 2006) has also been described for this plant.

To study the mechanism(s) of the relaxant effects of saffron, the stimulatory effect of aqueous-ethanolic extracts of Crocus sativus and one of its constituent, safranal on [beta]-adrenoceptors was examined on tracheal chains of guinea pigs.

Material and methods

Plant and extracts

Crocus sativus was collected from Torbat Heydarieh (east of Iran) and identified by Mrs. Molaei. A voucher specimen was preserved in the Herbarium of the School of Agriculture, Mashhad University of Ferdowsi (Herbarium no: 143-0319-1). The whole plant was collected and identified but only the stigma of the identified plant was isolated and used in the study. The aqueous-ethanolic extract of the isolated stigmata was prepared as follows: 10 g of chopped, dried isolated stigmata of the plant were extracted with 50 ml of ethanol 50% (25 ml distilled water and 25 ml ethanol) by soxhelt apparatus. The solvent was then removed under reduced pressure. The plant ingredient concentration in the final extract was adjusted to be 10 g% by adding distilled water to the dried extract.

Tissue preparations

Male Dunkin-Hartley guinea pigs (400-700 g) were scarified by a blow on the neck and the trachea were removed. Each trachea was cut into 10 rings (each containing 2-3 cartilaginous rings). All the rings were then cut open opposite the trachealis muscle, and sutured together to form tracheal chain (Holroyde, 1986).

Tissue was then suspended in a 10 ml organ bath (organ bath 61300, Bio Science Palmer-Washington, Sheerness, Kent UK) containing Krebs-Henseliet solution of the following composition (mM): NaCl 120, NaHC[O.sub.3] 25, MgS[O.sub.4] 0.5, K[H.sub.2]P[O.sub.4] 1.2, KCl 4.72. Ca[Cl.sub.2] 2.5, and dextrose 11.

The Krebs solution was maintained at 37 [degrees]C and gassed with 95% [O.sub.2] and 5% [CO.sub.2]. Tissue was suspended under isotonic tension (1 g) and allowed to equilibrate for at least 1 h while it was washed with Krebs solution every 15 min.

The study was approved by the University's Ethic Committee for animal use. The allowance number of the relevant ethical committee for the animal experiments is 85301.

Protocols

The stimulatory effect of different solutions was examined on [[beta].sub.2]-adrenoceptors by producing cumulative log concentration-response curves of isoprenaline sulphate (Sigma Chemical Ltd., UK)-induced relaxation of pre-contracted tracheal chains by 10 [mu]M methacholine hydrochloride (Sigma Chemical Ltd., UK) l0 min after exposing tissue to the tested solutions. Different tested solutions were included: l0 nM propranolol (0.1 ml of propranolol hydrochloride with 0.1 [mu]M concentration, Sigma Chemical Ltd., UK), two concentrations of aqueous-ethanolic extract from Crocus sativus (0.1 and 0.2 g% equivalent to 0.48 and 0.96 ml of 10 g% extract), safranal (1.25 and 2.5 [mu]g equivalent to 1 and 2ml of 10g% extract), or 0.2 ml saline. The consecutive concentrations of isoprenaline were added every 2 min (including 5 nM-1000 [mu]M); and the percentage of relaxation due to each concentration in proportion to the maximum relaxation obtained in the presence of saline was plotted against log concentration of isoprenaline.

The effective concentration of isoprenaline causing 50% of maximum response ([EC.sub.50]) in each experiment was measured using the isoprenaline-response curves of the corresponding experiment. The shift of cumulative log concentration-response curves obtained in the presence of extracts and propranolol were examined by comparing the ([EC.sub.50]) obtained in the presence of each solution with those of saline.

To examine the parallel shift, the slope of the curve of each experiment was measured and the slope of the isoprenaline curves obtained in the presence of extracts and propranolol were compared with those of saline. Maximum responses to isoprenaline obtained in the presence of extracts and propranolol were also compared with those of saline.

The shift in concentration-response curves (with a parallel shift compared to concentration-response curves obtained in the presence of saline) was assessed as concentration ratio minus one (CR-1) which was calculated by: ([EC.sub.50] obtained in the presence of active substraces/[EC.sub.50] obtained in the presence of saline)-1.

The stimulatory effect of Crocus sativus on [[beta].sub.2]-adrenoceptors was tested on two different experimental conditions as follows:

(a) Non-incubated tracheal chains (group 1, n = 9).

(b) Incubated tracheal chains 30 min prior to the beginning and while obtaining the isoprenaline curve with 1 [mu]M chlorpheniramine maleate (Sigma Chemical Ltd., UK), (group 2, n = 6).

All the experiments were randomly performed with 1 h resting period of tracheal chains between each two experiments while washing the tissues every 15 min with Krebs solution. In all experiments responses were recorded on a kymograph (ET8 G-Boulitt, Paris), and were measured after fixation. The study was approved by the Ethical Committee of our institution.

Statistical analysis

The data of [EC.sub.50], the slope of the curves, the values of (CR-1) and maximum response to isoprenaline in different experiments were expressed as mean [+ or -] SEM. The [EC.sub.50], the slope, and maximum response obtained in the presence of extract, safranal, and propranolol were compared with those obtained in the presence of saline and those of two different concentrations of extract and safranol using ANOVA with Tukey-Kramer multiple pot test. The values of (CR-1) obtained in the presence of extract and safranal, were also compared with those obtained in the presence of propranolol and those of two different concentrations of extract and safranol using ANOVA with Tukey-Kramer multiple pot test. The values of [EC.sub.50], the slope, (CR-1), and maximum response obtained in group 2 experiments were compared with those of group 1 using unpaired "t" test.

Results

Measurement of safranal and crocin of the same plant (Crocus sativus) was done in School of Pharmacy, Mashhad university of Medical Sciences using HPLC method. The two main constituents of the Crocus sativus were included: crocin (41.3%, crocin 2) and safranal (0.26%) (Hadizadeh et al., 2007).

Cumulative log concentration-response curves of isoprenaline obtained in the presence of only higher concentration of the extract showed clear leftward shift compared to the curve in the presence of saline in group 1. However, in group 2, concentration-response curves obtained in the presence of both concentrations of the extract and higher concentrations of safranal showed leftward shift compared to the curve in the presence of saline (Fig. 1).

[FIGURE 1 OMITTED]

The [EC.sub.50] of isoprenaline obtained in the presence of propranolol in both experimental conditions were significantly higher than those for saline (p < 0.05 for both cases). However, the [EC.sub.50] obtained in the presence of both concentrations of the extract and safranal in group 1 and only in the presence of two concentrations of the extract in group 2 were significantly lower than that of saline (p < 0.05-0.001) (Fig. 2). The [EC.sub.50] of isoprenaline obtained in the presence of saline, both concentrations of the extract, safranal and propranolol in group 2 were significantly higher than those of group 1 (p < 0.01-0.001) (Table 1). In addition, the [EC.sub.50] of isoprenaline obtained in the presence of higher concentrations of safranal and the extract from Crocus sativus only in group 2 showed significantly less compared to lower concentration (p< 0.02 for the both cases) (Table 1).

[FIGURE 2 OMITTED]
Table 1. [EC.sub.50] ([mu]M) of isoprenaline in the presence of
aqueous-ethanolic extract from Crocus sativus, safranal, 10nM
propranolol, and saline in two sets of experiments

Solutions Concentration Group 1 Group 2 Stat. Dif.
 group 1 vs
 group 2

Saline 1.00 4.06 p < 0.005
 [+ or -] [+ or -]
 0.22 1.04

Extract 0.1g% 0.17 1.16 p < 0.005
 [+ or -] [+ or -]
 0.06 0.31

 0.2 g% 0.12 0.68 p < 0.01
 [+ or -] [+ or -]
 0.02 0.21

Stat. Dif. 0.1 g% vs NS P <
0.2g% 0.02

Safranal 1.25 [mu]g 0.22 3.03 p < 0.01
 [+ or -] [+ or -]
 0.05 0.83

 2.5 [mu]g 0.12 2.10 p < 0.02
 [+ or -] [+ or -]
 0.06 0.64

Stat. Dif. 1.25 mg vs p < p <
2.5 mg 0.05 0.02

Stat. Dif. Saf. vs NS P <
Ext. (L. Conc.) 0.05

Stat. Dif. Saf. vs NS p <
Ext. (H. Conc.) 0.05

Propranolol 2.38 9.42 p < 0.01
 [+ or -] [+ or -]
 0.48 3.01

Values are presented as mean [+ or -] SEM. Group 1: experiments on non
incubated tracheal chains (n = 9); Group 2: experiments on tracheal
chains incubated with l [mu]M chlorpheniramine (n = 6). Stat. Dif.:
statistical difference, NS: non-significant difference.


The maximum response to isoprenaline obtained in the presence of both concentrations of the extract and safranal in group 1 was significantly lower than that of saline (p < 0.005 for all cases). However, in group 2, there was no significant difference between maximum response obtained in the presence of two concentrations of both extract and safranal compared to that of saline (Table 2). The maximum responses obtained in the presence of both concentrations of the extract and safranal in group 2 were significantly higher compared to group 1 (p < 0.05 for all cases) (Table 2). However, there was no significant difference between maximum responses obtained in the presence of two concentrations of the extract and safranal (Table 2).
Table 2. Maximum response to isoprenaline obtained in the presence of
extract from Crocus sativus, safranal, 10 nM propranolol, and saline
in the two sets of experiments

Solutions Concentration Group 1 Group 2 Stat. Dif. group 1
 vs group 2

Saline 97.20 91.00 NS
 [+ or -] [+ or -]
 1.44 2.41

Extract 0.1 g% 67.78 86.67 p < 0.05
 [+ or -] [+ or -]
 5.70 3.71

 0.2 g% 76.67 90.17 p < 0.05
 [+ or -] [+ or -]
 3.68 2.99

Stat. Dif. NS NS
0.1 g% vs
0.2g%

Safranal 1.25 [mu]g 66.50 83.60 p < 0.05
 [+ or -] [+ or -]
 5.18 4.96

 2.5 [mu]g 72.86 86.33 p < 0.05
 [+ or -] [+ or -]
 4.32 3.84

Stat. Dif. NS NS
1.25 mg vs
2.5mg

Stat. Dif. NS NS
Saf. vs Ext.
(L. Conc.)

Stat. Dif. NS NS
Saf. vs Ext.
(H. Conc.)

Propranolol 91.00 86.17 NS
 [+ or -] [+ or -]
 2.41 2.17

For abbreviations see Table 1.


The slopes of isoprenaline-response curves obtained in the presence of extracts from Crocus sativus and propranolol in both experimental conditions were not significantly different from those of saline. There was also no significant difference in the slopes of isoprenaline curve obtained in the presence of saline, two concentrations of the extract, safranal and propranolol between the two groups of experiments and also between two concentrations of the extract and safranal (Table 3).
Table 3. Slope of isoprenaline log concentration-response curves in the
presence of extract from Crocus sativus, safranal, 10nM propranolol,
and saline in two sets of experiments

Solutions Concentration Group 1 Group 2 Stat. Dif. group 1
 vs group 2

Saline -0.976 -0.943 NS
 [+ or -] [+ or -]
 0.004 0.006

Extract 0.1 g% -0.937 -0.898 NS
 [+ or -] [+ or -]
 0.023 0.027

 0.2 g% -0.956 -0.888 NS
 [+ or -] [+ or -]
 0.011 0.043

Stat. Dif. 0.1 NS NS
g% vs 0.2g%

Safranal 1.25 [mu]g -0.951 -0.915 NS
 [+ or -] [+ or -]
 0.020 0.044

 2.5 [mu]g -0.929 -0.915 NS
 [+ or -] [+ or -]
 0.020 0.044

Stat. Dif. 1.25 NS NS
mg vs 2.5 mg

Stat. Dif. Saf. NS NS
vs Ext. (L.
Conc.)

Stat. Dif. Saf. NS NS
vs Ext. (H.
Conc.)

Propranolol -0.942 -0.966 NS
 [+ or -] [+ or -]
 0.016 0.015

For abbreviations see Table 1.


All values of (CR-1)obtained in the presence of higher concentration of the extract in group 1, its both concentrations and higher concentration of safranal in group 2 were negative while those obtained in the presence of propranolol were positive. There was significant difference in this value between propranolol and those obtained in the presence of extract and safranal (p < 0.01-0.001) (Fig. 2). There was also no significant difference in the values of (CR-1) obtained in the presence of saline, two concentrations of the extract, safranal and propranolol between two groups of experiments and also between two concentrations of the extract (Table 4).
Table 4. Values of (CR-1) in the presence of extract from Crocus
sativus, safranal, and l0nM propranolol in two sets of experiments

 Stat. Dif. group 1
Solutions Concentration Group 1 Group 2 vs group 2

Extract 0.1 g% -1.07 -
 [+ or -]
 0.31

 0.2 g% -0.79 -1. 50 NS
 [+ or -] [+ or -]
 0.06 0.57

Stat. Dif. 0.1 NS
g% vs0.2g%

Safranal 1.25 [mu]g -- -- -

 2.5 [mu]g -- -0.39 -
 [+ or -]
 0.19

Stat. Dif. 1.25 -- NS
mg vs 2.5 mg

Stat. Dif. Saf. -- -
vs Ext. (L.
Conc.)

Stat. Dif. Saf. -- p <
vs Ext. (H. 0.05
Conc.)

Propranolol 1.91 2.14 NS
 [+ or -] [+ or -]
 0.15 0.51

For abbreviations see Table 1.


The [EC.sub.50] of isoprenaline obtained in the presence of both concentrations of the extract from Crocus sativus in group 2 were significantly lower than those of safranal (p < 0.05 for both concentrations) (Table 1). The value of (CR-1) obtained in the presence of higher concentrations of the extract in group 2 was significantly more negative than that obtained in the presence of safranal (p < 0.05) (Table 4).

Discussion

The bronchodilatory effect seen for Crocus sativus in our previous study (Boskabady and Aslani, 2006) might be produced due to several different mechanisms including stimulation of [beta]-adrenergic receptors, inhibition of histamine [H.sub.1] receptors or an anticholinergic property of the plant, because the relaxant effect of [[beta].sub.2] stimulatory (Martin et al., 1994; Linden et al., 1993), histamine [H.sub.1] receptro inhibitory (Popa et al., 1984) and anticholinergic drugs (Loenders et al., 1992) have been shown in previous studies. Therefore, the stimulatory effect of the aqueous-ethanolic extracts of Crocus sativus and its constituent, safranal, was examined on [beta]-adrenergic receptors of isolated guinea pig tracheal preparations.

The results on non-incubated trachea (group 1) showed a small parallel leftward shift of the isoprenaline concentration-response curves in the presence of only higher concentration of the extract of Crocus sativus compared to the curve in the presence of saline which indicated stimulatory effect of the extract on[[beta].sub.2] adrenoceptors.

To evaluate the stimulatory effect of extracts on [[beta].sub.2]-adrenoceptors more precisely, the effect of Crocus sativus was also examined on incubated tracheal preparation with chlorpheniramine to block histamine [H.sub.1] receptors (group 2 experiments). The results of group 2 experiments showed that both concentrations of the extract and higher concentrations of safranol caused parallel leftward shift in isoprenaline concentration-response curves indicating stimulatory effect of both concentrations of the extract and higher concentration of safranol on [[beta].sub.2]-adrenoceptors (Linden et al., 1993; Arunlakshana and Schild, 1959; Ariens, 1987).

The smaller values of [EC.sub.50] obtained in the presence of high concentration of the extract in group 1, both concentrations of the extract and high concentration of safranal in group 2 and negative values of (CR-1) confirm their stimulatory effect on [[beta].sub.2]-adrenoceptors. The smaller values of maximum response and [EC.sub.50] obtained in the presence of both concentrations of the extract and safranal may suggest an inhibitory effect for the extract of Crocus sativus and safranal on [H.sub.1] receptors. However, part of the differences in [EC.sub.50] between two groups (smaller values in group 1 compared to group 2) is at least, partially due to smaller values of maximum response in group 1.

The smaller values of [EC.sub.50] and more negative values of (CR-1) obtained in the presence of the extract compared to safranal may suggest that the stimulatory effect of the extract from Crocus sativus is partially due to safranal, particularly when it is emphasized that the equivalent concentrations for safranal were about five times greater than those for extract.

The results of the present study confirm those of our previous study indicating a potent relaxant effect for aqueous-ethanolic extracts of Crocus sativus which was almost entirely absent in tracheal chains incubated with propranolol, cholorpheniramine, and atropine (Boskabady and Aslani, 2006). In addition, our previous study (Boskabady and Aslani, 2006) also showed that the relaxant effect of the extract of Crocus sativus was significantly greater than that of safranal at used concentration, indicating that the relaxant effect of the plant is partially due to safranal.

The HPLC results for the same plant indicating that the extract of Crocus sativus contains only 0.26% safranal while the amount of crocin in the extract was 41.3%. The results of our previous study showed a potent relaxant effect of saffron and safranal on tracheal chains of guinea pigs. Therefore, in this study the stimulatory effect of safranal on [beta]-adrenergic receptors of isolated guinea pig trachea was studied. However, the stimulatory effect of crocin on [beta]-adrenergic receptors should be evaluated in further studies.

Although safranal contains an aldehyde group which expected to be unstable and metabolized very fast, however, Kanakis et al. (2007) showed that safranal binds with human serum albumin and has relatively stable antioxidative properties. In addition the results of the present study showed that the stimulatory effect of the extract of Crocus sativus on [beta]-adrenergic receptors is partially due to safranal. Therefore the expected instability for safranal is should not be the case for other constituents of the plant which are mainly responsible for this effect of the plant. In fact, several studies showed different stable clinical property of the plant which confirms its stability and long duration therapeutic effects. The results of the study of AghaHosseini et al. (2008) indicated the therapeutic effect of 30mg/day saffron on premenstrual syndrome for a two menstrual cycles. The antidepressant effect of 30 mg daily saffron for 8-week period (Akhondzadeh Basti et al., 2007) and the same effect for hydro-alcoholic extract of Crocus sativus for 6 weeks time (Noorbala et al., 2005) has been also shown. Regarding the cost of the plant, its effective amount is very minute and therefore the cost of its therapeutic dose is comparable with the available [beta]-adrenergic agonists. In fact, Chatterjec et al. (2005) showed that the cost of Indian saffron which is very similar to Iranian plant is almost 38 times less per unit dry weight compared to the 'Sigma' saffron. Therefore, as stated by Schmidt et al. (2007), saffron extracts have the potential to make a major contribution to rational phytotherapy. Based on the results of the present study, the potent relaxant effect of the extract from Crocus sativus on tracheal chains (greater than theophylline with a minute dose) observed in our previous study (Boskabady and Aslani, 2006) is suggested to be due to its stimulatory effect on [beta]-adrenergic receptors. Therefore, this property of the plant may be superior to available [beta]-adrenergic agonists and require further studies.

In conclusion, the results of this study showed a relatively potent stimulatory effect of the extract of Crocus sativus on [[beta].sub.2]-adrenoceptors which was partially due to one of its constituent, safranal. A possible inhibitory effect of the plant on histamine ([H.sub.1]) receptors was also suggested.

Acknowledgements

This study was financially supported by Research Department of Mashhad University of Medical sciences. The authors would also like to thank Dr. F. Hadizadeh, Dr. Emami, and Dr. Hassanzadeh Khiat for their help in HPLC measurement of safranal and crocin.

References

Abdullaev, F.I., Espinosa-Aguirre, J.J., 2004. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect. Prev. 28, 426-432.

Abdullaev, F.J., 1993. Biological effects of saffron. Biofactors 4, 83-86.

Abdullaev, F.J., Ferenkel, G.D., 1992. Effects of saffron on cell colony formation and cellular nucleic acid and protein synthesis. Biofactors 3, 201-204.

Abe, K., Saito, H., 2000. Effects of saffron extract and its constituent crocin on learning behaviour and long-term potentiation. Phytother. Res. 14, 149-152.

Abe, K., Sugiura, M., Ymaguchi, S., Shoyama, Y., Saito, H., 1999. Saffron extract prevents acetaldehyde-induced inhibition of long-term potentiation in the rat dentate gyrus invivo. Brain Res. 851, 287-289.

Agha-Hosseini, M., Kashani, L., Aleyaseen, A., Ghoreishi, A., Rahmanpour, H., Zarrinara, A.R., Akhondzadeh, S., 2008. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. B.J.O.G. 115, 515-519.

Akhondzadeh, S., Tahmacebi-Pour, N., Noorbala, A.A., Amini, H., Fallah-Pour, H., Jamshidi, A.H., Khani, M., 2005. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother. Res. 19, 148-151.

Akhondzadeh Basti, A., Moshiri, E., Noorbala, A.A., Jamshidi. A.H., Abbasi, S.H., Akhondzadeh, S., 2007. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog. Neuropsychopharmacol. Biol. Psychiatry 31, 439-442.

Ariens, E.J., 1987. Pharmacology of the airway smooth muscle. In: Nadel, J.A., Pauweis, R., Snashall, P.D, (Eds.), Bronchial Hyperresponsiveness. Blackwell Scientific Publications, London, pp. 7-23.

Arunlakshana, O., Schild. H.O., 1959. Some quantitive use of drug antagonist. Br. J. Phamacol. 14, 48-58.

Assimopoulou, A.N., Sinakos, Z., Papageorgiou, V.P., 2005. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother. Res. 19, 997-1000.

Boskabady, M.H., Aslani. M.R., 2006. Relaxant effect of Crocus sativus on guinea pig tracheal chains and its possible mechanisms. J. Pharm. Pharmacol. 58, 1385-1390.

Chatterjee, S., Poduval, T.B., Tilak, J.C., Devasagayam, T.P., 2005. A modified, economic, sensitive method for measuring total antioxidant capacities of human plasma and natural compounds using Indian saffron (Crocus sativus). Clin. Chim. Acta 352. 155-163.

Chryssanthi, D.G., Lamari, F.N., Iatrou, G., Pylara, A., Karamanos, N.K., Cordopatis, P., 2007. Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. Anticancer Res. 27, 357-362.

Das, I., Chakrabarty, R.N., Das, S., 2004. Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice. Asian Pac. J. Cancer Prev. 4, 70-76.

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

Fatehi, M., Rashidabady, T., Fatehi-Hassanabad, Z., 2003. Effects of Crocus stivus petals extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum. J. Ethanopharmacol. 84, 199-203.

Hadizadeh, F., Mahdavi, M., Emami, S.A., Khashayarmanesh, Z., Hassanzadeh, M., Asili, J., Seifi, M., Nassirli, H., 2007. Evaluation of ISO method in saffron qualification. Acta Hortic. (ISHS) 739, 405-409.

Holroyde, M.C., 1986. The influence of epithelium on the responsiveness of guinea pig isolated trachea. Br. J. Pharmacol. 87, 501-507.

Hosseinzadeh, H., Khosravan, V., 2002. Anticonvulsant effects of aqueous and ethanolic extracts of Crocus sativus L. stigmas in mice. Arch. Irn. Med. 5, 44-47.

Hosseinzadeh, H., Talebzadeh, F., 2005. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia 76, 722-724.

Hosseinzadeh, H., Younesi, H.M., 2002. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2, 1-8.

Hosseinzadeh, H., Karimi, G.H., Niapoor, M., 2004. Antidepressant effects of Crocus sativus stigma extracts and its constituents, crocin and safranal, in mice. Acta Hortic. (ISHS) 650, 435-444.

Kanakis, C.D., Tarantilis, P.A., Tajmir-Riahi, H.A., Polissiou, M.G., 2007. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J. Agric. Food Chem. 55, 970-977.

Linden, A., Bergendal, A., Ullman, A., Skoogh, B.E., Lofdahl, C.G., 1993. Salmetrol, formetrol, and salbutamol in the isolated guinea-pig trachea: differences in maximum relaxant effect and potency but not in functional antagonism. Thorax 48, 547-553.

Loenders, B., Rampart, M., Herman, A.G., 1992. Selective [M.sub.3] muscarinic receptor inhibit smooth muscle contraction in rabbit trachea without increasing the release of acetylcholine. J. Pharmacol. Exp. Ther. 263, 773-779.

Martin, C.A.E., Naline, E., Bakdach, H., Advenier, C., 1994. [[Beta].sub.3] adrenoceptor agonists, BRL 37344 and SR 58611A do not induce relaxation of human, sheep and guinea pig airway smooth muscle in vitro. Eur. Respir. J. 7, 1610-1615.

Nair, S.C., Kurumboor, S.K., Hasegawa, J.H., 1995. Saffron chemoprevention in biology and medicine: a review. Cancer Biother. 10, 257-264.

Noorbala, A.A., Akhondzadeh, S., Tahmacebi-Pour, N., Jamshidi, A.H., 2005. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J. Ethnopharmacol. 97, 281-284.

Papandreou, M.A., Kanakis, C.D., Polissiou, M.G., Efthimiopoulos, S., Cordopatis, P., Margarity, M., Lamari, F.N., 2006. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J. Agric. Food Chem. 54, 8762-8768.

Pitsikas, N., Sakellaridis, N., 2006. Crocus sativus L. extracts antagonize memory impairments in different behavioural tasks in the rat. Behav. Brain Res. 173, 112-115.

Popa, V.T., Somani, P., Simon, P., Simon, V., 1984. The effect of inhaled verapamil on resting bronchial tone and airway constriction by histamine and acetylcholine in normal and asthmatic subjects. Am. Rev. Respir. Dis. 130, 106-113.

Premkumar, K., Abraham, S.K., Santhiya, S.T., Gopinath, P.M., Ramesh, A., 2001. Inhibition of genotoxicity by saffron (Crocus sativus L.) in mice. Drug Chem. Toxicol. 24, 421-428.

Premkumar, K., Abraham, S.K., Santhiya, S.T., Ramesh, A., 2003. Protective effects of saffron (Crocus sativus L.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother. Res. 17, 614-617.

Premkumar, K., Thirunavukkarasu, C., Abraham, S.K., Santhiya, S.T., Ramesh A.. 2006. Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice. Hum. Exp. Toxicol. 25, 79-84.

Rios, J.L., Recio, M.C., Giner, R.M., Manz, S., 1996. An update review of saffron and its active constituents. Phytother. Res. 10, 189-193.

Schmidt, M., Betti, G., Hensel, A., 2007. Saffron in phytotherapy: pharmacology and clinical uses. Wien. Med. Wochenschr. 157, 315-319.

Trantilis, P.A., Tsoupras, G. Polissiou, M., 1995. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatograghy-UV-visible photodiode-array detection-mass spectrometry. J. Chromatogr. 99, 107-111.

Verma, S.K., Bordia, A., 1998. Antioxidant property of saffron in man. Indian J. Med. Sci. 52, 205-207.

Zhang, Y.X., Sugiura, M., Saito, H., Shoyama, Y., 1994. Acute effects of Crocus sativus L. on passive avoidance performance in mice. Biol. Pharmacol. Bull. 17, 217-221.

H. Nemati, M.H. Boskabady *,H. Ahmadzadef Vostakolaei

Department of Physiology and Pharmacology Research Centre of Medicinal Plants, Medical School, Mashhad University of Medical Sciences, Mashhad, Khorassan 91735, Iran

* Corresponding author. Tel.: +98 511 800221;

fax: +98 511 8828566.

E-mail addresses: mhboskabady@hotmail.com.

boskabadymh@mums.ar.ir (M.H. Boskabady).

0944-7113/$-see front matter [C] 2008 Elsevier GmbH. All rights reserved.

doi: 10.1016/j.phymed.2008.07.008
COPYRIGHT 2008 Urban & Fischer Verlag
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2008 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Nemati, H.; Boskabady, M.H.; Vostakolaei, H.Ahmadzadef
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Clinical report
Geographic Code:7IRAN
Date:Dec 1, 2008
Words:5265
Previous Article:Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers.
Next Article:Danggui-Shaoyao-San, a traditional Chinese prescription, suppresses [PGF.sub.2.[alpha]] production in endometrial epithelial cells by inhibiting...
Topics:

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters