ORIGINAL_ARTICLE
Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms
Saffron, Crocus sativus L. (C. sativus) is rich in carotenoids and used in traditional medicine for treatment of various conditions such as coughs, stomach disorders, amenorrhea, asthma and cardiovascular disorders. These therapeutic effects of the plant are suggested to be due to its relaxant effect on smooth muscles. The effect of C. sativus and its constituents on different smooth muscles and the underlying mechanisms have been studied. Several studies have shown the relaxant effects of C. sativus and its constituents including safranal, crocin, crocetin and kaempferol on blood vessels. In addition, it was reported that saffron stigma lowers systolic blood pressure. The present review highlights the relaxant effects of C. sativus and its constituents on various smooth muscles. The possible mechanisms of this relaxing effect including activation of ß2-adrenoceptors, inhibition of histamine H1 and muscarinic receptors and calcium channels and modulation of nitric oxide (NO) are also reviewed.
https://ajp.mums.ac.ir/article_4452_8231f45f9dcfd466807be0cdcaf907e1.pdf
2015-09-01
365
375
10.22038/ajp.2015.4452
Crocus sativus, Saffron, Crocin, Smooth muscle, Relaxant effect
Possible mechanisms
Amin
Mokhtari-Zaer
mokhtaria921@mums.ac.ir
1
Neurogenic Inflammation Research Centre and Dept. of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammad Reza
Khazdair
khazdeirmr921@mums.ac.ir
2
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammad Hossein
Boskabady
boskabadymh@mums.ac.ir
3
Neurogenic Inflammation Research Centre and Dept. of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
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ORIGINAL_ARTICLE
The effects of Crocus sativus (saffron) and its constituents on nervous system: A review
Saffron or Crocus sativus L. (C. sativus) has been widely used as a medicinal plant to promote human health, especially in Asia. The main components of saffron are crocin, picrocrocin and safranal. The median lethal doses (LD50) of C. sativus are 200 mg/ml and 20.7 g/kg in vitro and in animal studies, respectively. Saffron has been suggested to be effective in the treatment of a wide range of disorders including coronary artery diseases, hypertension, stomach disorders, dysmenorrhea and learning and memory impairments. In addition, different studies have indicated that saffron has anti-inflammatory, anti-atherosclerotic, antigenotoxic and cytotoxic activities. Antitussive effects of stigmas and petals of C. sativus and its components, safranal and crocin have also been demonstrated. The anticonvulsant and anti-Alzheimer properties of saffron extract were shown in human and animal studies. The efficacy of C. sativus in the treatment of mild to moderate depression was also reported in clinical trial. Administration of C. sativus and its constituents increased glutamate and dopamine levels in the brain in a dose-dependent manner. It also interacts with the opioid system to reduce withdrawal syndrome. Therefore, in the present article, the effects of C. sativus and its constituents on the nervous system and the possible underlying mechanisms are reviewed. Our literature review showed that C. sativus and its components can be considered as promising agents in the treatment of nervous system disorders.
https://ajp.mums.ac.ir/article_4503_4063c5b57e008139e828510da8bc4054.pdf
2015-09-01
376
391
10.22038/ajp.2015.4503
Crocus sativus
Nervous system
Safranal
Crocin, Saffron
Mohammad Reza
Khazdair
khazdeirmr921@mums.a.cir
1
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammad Hossein
Boskabady
boskaabdymh@mums.ac.ir
2
Neurogenic Inflammation Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Postal Code 9177948564, Iran
AUTHOR
Mahmoud
Hosseini
hosseinim@mums.ac.ir
3
Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Postal Code 9177948564, Iran
LEAD_AUTHOR
Ramin
Rezaee
rezaeer871@mums.ac.ir
4
Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
AUTHOR
Aristeidis
M. Tsatsakis
5
Center of Toxicology Science and Research, Division of Morphology, Medical School, University of Crete, Heraklion, Crete, Greece
AUTHOR
Abdullaev F. 1993. Biological effects of saffron. BioFactors (Oxford, England), 4:83-86
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ORIGINAL_ARTICLE
Effects of crocin and safranal, saffron constituents, on the formalin-induced orofacial pain in rats
Objective: Crocin and safranal are the main components of saffron, and have many biological functions such as anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of crocin, safranal, morphine, diclofenac and naloxone in combined and separately on formalin-induced orofacial pain in rats. Materials and Methods: Subcutaneous injection of a diluted formalin solution (50 µl, 1.5%) into the upper lip region produced a biphasic pattern of pain response (a neurogenic phase: 0-3 min and an inflammatory phase: 15-33 min). The time each animal spent face rubbing with ipsilateral forepaw was recorded and considered as an index of nociception Results: Intraperitoneal injections of crocin (12.5 and 25 mg/kg), safranal (0.25 and 0.5 mg/kg), diclofenac (5 and 10 mg/kg) and morphine (1 and 2 mg/kg) suppressed the second phase of pain. The second phase of pain was also reduced when low (ineffective) doses of crocin (6.25 mg/kg) and safranal (0.125 mg/kg) were co-administered with low doses of diclofenac (2.5 mg/kg) and morphine (0.5 mg/kg). The more antinociceptive effects were observed when the medium doses of the above-mentioned chemicals used together. Naloxone prevented morphine-induced antinociception, but did not inhibit the suppressive effects of crocin and safranal. Safranal at a high dose (0.5 mg/kg) suppressed locomotor activity. Conclusion: The present results showed antinociceptive effects for crocin and safranal in inflammatory pain. Opioid receptors may not be involved in the antinociceptive effect of crocin and safranal. Crocin and safranal increased diclofenac-induced antinociception.
https://ajp.mums.ac.ir/article_3083_a6013f458c523882f39dd2b5d352fd84.pdf
2015-09-01
392
402
10.22038/ajp.2015.3083
Crocin
Safranal
Diclofenac
Orofacial pain
Rats
Amir
Erfanparast
amirerfan80@yahoo.com
1
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia Universiry, Urmia 57153-1177, I. R. Iran
LEAD_AUTHOR
Esmaeal
Tamaddonfard
e_tamaddonfard@yahoo.com
2
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia Universiry, Urmia 57153-1177, I. R. Iran
AUTHOR
Mina
Taati
minataati@gmail.com
3
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia Universiry, Urmia 57153-1177, I. R. Iran
AUTHOR
Milad
Dabbaghi
miladdabaghi68@gmail.com
4
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia Universiry, Urmia 57153-1177, I. R. Iran
AUTHOR
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Tamaddonfard E, Hamzeh-Gooshchi N. 2010b. Effects of intraperitoneal and intracerebroventricular injection of crocin on acute corneal pain in rats. Phytother Res, 24: 1463-1467.
47
Tjolsen A, Berge OG, Hunskaar S, Rosland GH, Hole K. 1992. The formalin test: an evaluation of the method. Pain, 51: 5-17.
48
Torpe LB, Goldie M, Dolan S. 2011. Central and local administration of Gingko biloba extract EGb 761 ® inhibits thermal hyperalgesia and inflammation in the rat carrageenan model. Anesth Analg, 112: 1226-1231.
49
Vane JR, Botting RM. 1996. Mechanisms of action of anti-inflammatory drugs. Scand J Rheumatol, 102: 9–21.
50
Wolfe MM, Lichtenstein DR, Singh G. 1999. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med, 370: 1888-1899.
51
Xu GL, Li G, Ma HP, Zhong H, Liu F, Ao GZ. 2009. Preventive effect of crocin in inflamed animals and in LPS-challenged RAW 264.7 cells. J Agric Food Chem, 57: 8325-8330.
52
ORIGINAL_ARTICLE
Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats
Objectives:Crocin is one of constituents of saffron and has antioxidant property. Zinc chloride is one of the common compounds of zinc with antioxidant activity. The present study was aimed to investigate separate and combined treatment effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in diabetic rats. Materials and Methods:Diabetes was induced by intraperitoneal (i.p.) injection of 50 mg/kg of streptozotocin (STZ) and was confirmed by blood glucose levels higher than 250 mg/dL. After confirmation of diabetes, injections (i.p.) of crocin and zinc chloride were performed for six weeks. At the end of the experiment, blood levels of zinc, glucose, insulin, malodialdehyde (MDA), and total antioxidant capacity (TAC) were measured. Results:Crocin (25 and 50 mg/kg) and zinc chloride (5 mg/kg) significantly recovered the decreased levels of zinc, insulin, and TAC and improved the increased levels of glucose and MDA in STZ-induced diabetic rats. In a combination treatment performed with an ineffective dose of crocin (12.5 mg/kg) and a low dose of zinc chloride (1.25 mg/kg), improving effects were observed on the above-mentioned biochemical parameters. Conclusions: The results indicated that separate and combined treatments with crocin and zinc chloride produced improving effects on the blood levels of zinc, glucose, insulin, MDA and TAC in STZ-induced diabetic rats.
https://ajp.mums.ac.ir/article_3309_dc58a48736686190b08a3030e38105c1.pdf
2015-09-01
403
412
10.22038/ajp.2015.3309
Crocin
Rats
Diabets
zinc
Siamak
Asri-Rezaei
siamak.asri@gmail.com
1
Division of Clinical Pathology, Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
AUTHOR
Esmaeal
Tamaddonfard
e_tamaddonfard@yahoo.com
2
Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
LEAD_AUTHOR
Behnaz
Gasemsoltani-Momtaz
behnazsoltani2012@gmail.com
3
Division of Clinical Pathology, Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
AUTHOR
Amir
Erfanparast
amirerfan80@yahoo.com
4
Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
AUTHOR
Sima
Gholamalipour
simagholamalipour@gmail.com
5
Division of Clinical Pathology, Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
AUTHOR
Abou-Seif MA, Youssef AA. 2004. Evaluation of some biochemical changes in diabetic patients. ClinChimActa, 346: 161-170.
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Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M, Ahmadi M, Shafiee S. 2013. Antihyperglycemic and antioxidant activity of crocin in streptozotocin-induced diabetic rats. J Med Food, 16: 206-210.
27
Shirali S, Zahra Bathaie S, Nakhjavani M. 2013. Effect of crocin on the insulin resistance and lipid profile of stereptozotocin-induced diabetic rats.Phytother Res, 27: 1042-1047.
28
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29
Tamaddonfard E, Farshid AA, Ahmadian E, Hamidhoseyni A. 2013a. Crocin enhanced functional recovery after sciatic nerve crush injury in rats. Iran J Basic Med Sci, 16: 83-90.
30
Tamaddonfard E, Farshid AA, Asri-Rezaee S, Javadi Sh, Khosravi V, Rahman B, Mirfakhraee Z. 2013b.Crocin improved learning and memory impairment in streptozotocin-induced diabetic rats. Iran J Basic Med Sci, 16: 91-100.
31
Tamaddonfard E, Farshid AA, Eghdami K, Samadi F, Erfanparast E. 2013c. Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats.Pharmacol Rep, 65: 1272-1280.
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34
Tamaddonfard E, Hamzeh-Gooshchi N. 2010a. Effect of crocin on the morphine-induced antinociception in the formalin test in rats.Phytother Res, 24: 410-413.
35
Tamaddonfard E, Hamzeh-Gooshchi N. 2010b Effects of intraperitoneal and intracerebroventricular injection of crocin on acute corneal pain in rats.Phytother Res, 24: 1463-1467.
36
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44
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45
Zhu K, Nie S, Li C, Huang J, Hu X, Li W, Gong D, Xie M. 2013. Antidiabetic and pancreatic-protective effects of zinc threoninate chelate in diabetic rats may be associated with its antioxidant stress ability. Biol Trace Elem Res, 153: 291-298.
46
ORIGINAL_ARTICLE
Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia
Objectives: Saffron is the stigma of Crocus sativus L., which has the potentials to play a role in the treatment of many diseases. Although many researches are now going on this precious spice, there are few data on saffron safety in human, especially in patients with chronic mental illnesses. This study aimed to evaluate the short-term safety and tolerability of both saffron and crocin (its major constituent) in adult patients with schizophrenia. Materials and Methods: The capsules of saffron aqueous extract (SAE) and crocin were used to evaluate short-term safety and tolerability in patients with schizophrenia. A double-blind, placebo-controlled study was performed on patients with schizophrenia. The patients were all male and were divided into three 22-patient groups. While receiving their normal treatment, they also received a 12 week treatment with SAE (15 mg twice daily), crocin (15 mg twice daily) or placebo. Results: A total of 61 patients completed the trial; none of them reported a serious side effect. WBC count increased significantly in patients receiving saffron aqua extract (SAE), but it was within the normal range and had no clinical significance. Other hematologic components, markers of thyroid, liver and kidney or inflammation markers had no statistically significant difference among the groups. Conclusions: This study showed that SAE and crocin in doses of 15 mg twice daily were safely tolerated in patients with schizophrenia.
https://ajp.mums.ac.ir/article_3879_55c86cf7be3302b739a21de47b970bb2.pdf
2015-09-01
413
419
10.22038/ajp.2015.3879
Saffron Aqueous Extract
Crocin
Clinical trial
Safety assessment
Schizophrenia
Bentolhoda
Mousavi
b_mousavi@ymail.com
1
Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, P.O.Box: 1985713834, Tehran, Iran
AUTHOR
Seyedeh zahra
Bathaie
bathai_z@modares.ac.ir
2
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, P.O.Box: 14115-111, Tehran, Iran
LEAD_AUTHOR
Farbod
Fadai
farbodfadai@uswr.ac.ir
3
Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, P.O.Box: 1985713834, Tehran, Iran
AUTHOR
Zabihollah
Ashtari
zabih_ashtari@yahoo.com
4
Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, P.O.Box: 1985713834, Tehran, Iran
AUTHOR
Neda
Ali beigi
nedapsych@yahoo.com
5
Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, P.O.Box: 1985713834, Tehran, Iran
AUTHOR
Sara
farhang
dsfarhang@gmail.com
6
Clinical psychiatry research center, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Sara
Hashempour
dr.hashempour.sara@gmail.com
7
Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, P.O.Box: 1985713834, Tehran, Iran
AUTHOR
Nasim
Shahhamzei
n.shahhamzei@yahoo.com
8
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, P.O.Box: 14115-111, Tehran, Iran
AUTHOR
Hamid
Heidarzadeh
hami_heidarzadeh@yahoo.com
9
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, P.O.Box: 14115-111, Tehran, Iran
AUTHOR
Akhondzadeh S, Sabet MS, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi S, Yousefi MH, Alimardani R, Jamshidi A, Zare F , Moradi A. 2010. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial. J Clin Pharm Ther, 35: 581-588.
1
Akhondzadeh S, Shafiee Sabet M, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SS, Yousefi MH, Alimardani R, Jamshidi A, Rezazadeh SA, Yousefi A, Zare F, Moradi A ,Vossoughi A. 2010. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology (Berl), 207: 637-643.
2
Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH , 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.
3
Ayatollahi H, Javan AO, Khajedaluee M, Shahroodian M , Hosseinzadeh H. 2014. Effect of Crocus sativus L.(Saffron) on Coagulation and Anticoagulation Systems in Healthy Volunteers. Phytother Res, 28: 539-43.
4
Cai T, Morgia G, Carrieri G, Terrone C, Imbimbo C, Verze P, Mirone V, Group IGS. 2013. An improvement in sexual function is related to better quality of life, regardless of urinary function improvement: Results from the IDIProst® Gold Study. Archivio Italiano di Urologia e Andrologia, 85: 184-189.
5
Fadai F, Mousavi B, Ashtari Z, Ali Beigi N, Farhang S, Hashempour S, Shahhamzei N ,Bathaie SZ. 2014. Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: a randomized triple blind placebo controlled study. Pharmacopsychiatry, 47: 156-161.
6
Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, Haghighi S, Sameni HR, Pahlvan S. 2011. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol, 667: 222-229.
7
Hausenblas HA, Saha D, Dubyak PJ ,Anton SD. 2013. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integrative Med, 11: 377-383.
8
Hert M, Schreurs V, Vancampfort D ,Winkel R. 2009. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry, 8: 15-22.
9
Hosseinzadeh H, Modaghegh MH , Saffari Z. 2009. Crocus Sativus L. (Saffron) Extract and its Active Constituents (Crocin and Safranal) on Ischemia-Reperfusion in Rat Skeletal Muscle. Evidence-Based Complement Alternat Med, 6: 343-350.
10
Hosseinzadeh H ,Younesi HM. 2002. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol, 2: 7.
11
Imenshahidi M, Razavi BM, Faal A, Gholampoor A ,Mehran S. 2013. The Effect of Chronic Administration of Saffron (Crocus sativus) Stigma Aqueous Extract on Systolic Blood Pressure in Rats. Jundishapur J Nat Pharm Prod, 8: 175-179.
12
Kashani L, Raisi F, Saroukhani S, Sohrabi H, Modabbernia A, Nasehi AA, Jamshidi A, Ashrafi M, Mansouri P, Ghaeli P , Akhondzadeh S. 2013. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study. Hum Psychopharmacol, 28: 54-60.
13
Moallem SA, Hariri AT, Mahmoudi M , Hosseinzadeh H. 2014. Effect of aqueous extract of Crocus sativus L.(saffron) stigma against subacute effect of diazinon on specific biomarkers in rats. Toxicol Indust Health, 30: 141-146.
14
Modaghegh MH, Shahabian M, Esmaelli HA, Rajbai O ,Hosseinzadeh H. 2008. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers. Phytomedicine, 15: 1032-1037.
15
Mohajeri D, Mousavi G, Mesgari M, Doustar Y ,Khayat Nouri MH. 2007. Subacute Toxicity of Crocus Sativus L. (Saffron) Stigma Ethanolic Extract in Rats. Am J Pharmacol Toxicol, 2: 189-193.
16
Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O ,Hosseinzadeh H. 2013. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci, 16: 39.
17
Mulholland C ,Cooper S. 2000. The symptom of depression in schizophrenia and its management. Adv Psychiatric Treat, 6: 169-177.
18
Papandreou MA, Tsachaki M, Efthimiopoulos S, Cordopatis P, Lamari FN ,Margarity M. 2011. Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection. Behav Brain Res, 219: 197-204.
19
Ramadan A, Soliman G, Mahmoud SS, Nofal SM , Abdel-Rahman RF. 2012. Evaluation of the safety and antioxidant activities of< i> Crocus sativus and< i> Propolis ethanolic extracts. J Saudi Chem Soci, 16: 13-21.
20
Samarghandian S, Borji A, Farahmand SK, Afshari R, Davoodi S. 2013. Crocus sativus L.(Saffron) Stigma Aqueous Extract Induces Apoptosis in Alveolar Human Lung Cancer Cells through Caspase-Dependent Pathways Activation. BioMed Res Int, 2013: 1-12.
21
Shahmansouri N, Farokhnia M, Abbasi S-H, Kassaian SE, Noorbala Tafti A-A, Gougol A, Yekehtaz H, Forghani S, Mahmoodian M ,Saroukhani S. 2014. A randomized, double-blind, clinical trial comparing the efficacy and safety of< i> Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. J Affective Disorders, 155: 216-222.
22
Shirali S, Bathaie SZ, Nakhjavani M. 2013. Effect of crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats. Phytother Res, 27: 1042-1047.
23
Shirali S, Bathaie SZ, Nakhjavani M ,Ashoori MR. 2012. Effects of saffron (Crocus Sativus L.) aqueous extract on serum biochemical factors in streptozotocin-induced diabetic rats. Iranian J Med Aroma Plants, 28: 293-308.
24
ORIGINAL_ARTICLE
Effect of crocin on nitric oxide synthase expression in post-ischemic isolated rat heart
Objective: Oxidative stress damages cells and brings about the pathogenesis of ischemia/reperfusion injury. This study was carried out to investigate the preconditioning and cardio protective potential effects of crocin and vitamin E by the eNOS and iNOS express gene in ischemia/reperfusion in rats. Material & Methods: Male rats were divided into seven groups, namely: sham, control group and experimental groups treated with crocin(10, 20 and 40 mg/kg), vitamin E (100 mg/kg) and combination of crocin (40 mg/kg) with vitamin E (100 mg/kg) that were gavaged The heart was removed and relocated to a Langendorff apparatus and subjected to global ischemia and then the left ventricular end diastolic pressure (LVEDP) were measured as a hemodynamic parameter. Total RNA was extracted from heart frozen tissues. RT-PCR technique was performed by specific primers designed for nitric oxide gene and the results were assessed by agarose gel electrophoresis. Results: Results after ischemia and reperfusion showed that crocin 40 mg/kg produced a significant improvement of LVEDP as a mechanical function (P<0.05), associated with a reduction of iNOS release (P<0.05). The eNOS mRNA levels were significantly higher in crocin-treated 40 mg/kg compared to controls treated by RT-PCR technique. The combination of crocin and vitamin E have shown more effective on the reduction of iNOS release (P<0.01). Conclusion: In the isolated rat heart, protective effect of crocin, may possibly be explained by regulating eNOS and iNOS expressions. The Results resultsconfirmed the hypothesis that cardioprotective effect of crocin is partly mediated by nitric oxide. This could explain the cardioprotective action of crocin following ischemia and reperfusion.
https://ajp.mums.ac.ir/article_3755_b95e18e0680b8d3cde73c378c660a222.pdf
2015-09-01
420
426
10.22038/ajp.2015.3755
Ischemia-reperfusion injury
Crocin
Vitamin E
iNOS protein
eNOS protein
Rat
Mahdi
Esmaeilizadeh
mahdiesmaeilizadeh@yahoo.com
1
Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
AUTHOR
Mahin
Dianat
dianat@ajums.ac.ir
2
Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
LEAD_AUTHOR
Mohammad
Badavi
badavim@yahoo.com
3
Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
AUTHOR
Alireza
Samarbaf-zadeh
samarbaf-a@ajums.ac.ir
4
Department of Virology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
AUTHOR
Bahareh
Naghizadeh
naghizadeh-b@ajums.ac.ir
5
Department of Pharmacology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
AUTHOR
Abdullaev FI, Espinosa-Aguirre JJ. 2004. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev, 28: 426-432.
1
Assimopoulou AN, Sinakos Z, Papageorgiou VP. 2005. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. PhytotherRes,19:997-1000.
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Atochin DN, Huang PL. 2010. Endothelial nitric oxide synthase transgenic models of endothelial dysfunction. Pflugers Arch, 460: 965-74.
3
Barouch LA, Harrison RW, Skaf MW, Rosas GO, CappolaTP, Kobeissi ZA, et al. 2002. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature, 416: 337-339.
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6
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7
Dianat M, Esmaeilizadeh M, Badavi M, Samarbaf-Zadeh AR, Naghizadeh B. 2014a. Protective Effects of Crocin on Ischemia-reperfusion Induced Oxidative Stress in Comparison With Vitamin E in Isolated Rat Hearts. Jundishapur J Nat Pharm Prod, 9: e17187.
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9
Dianat M, Esmaeiliziadeh M, Badavi M, Samarbafzadeh A, Naghizadeh B. 2014b. Cardiac protective effects of crocin on hemodynamic parameters and infarct size in compare vitamin E after ischemia reperfusion in isolated rat heart. Planta Med, 80: 393-398.
10
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Garcıa-Villalon AL, Monge L, Fernandez N, Salcedo A. 2009. Coronary response to diadenosinepentaphosphate after ischaemia– reperfusion in the isolated rat heart. Cardiovascular Research, 81: 336-343.
13
Goldspink DF, Burniston JG, Ellison GM, Clark WA, Tan LB. 2004. Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo: the same or separate death pathways. ExpPhysiol, 89: 407-416.
14
Gyurko R, Kuhlencordt P, Fishman MC, Huang PL. 2002. Modulation of mouse cardiac function in vivo by eNOS and ANP. Am J Physiol Heart CircPhysiol, 78: 971-981.
15
Hosseinzadeh H, Ziaei T. 2006a. Effects of Crocus sativus stigma extract and its constituents, crocin and safranal, on intact memory and scopolamine-induced learning deficits in rats performing the Morris water maze task. J Med Plant, 5: 40-48.
16
Hosseinzadeh H, Shamsaie F, Mehri S. 2009b. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituent, crocin and safranal. Pharmacogn Mag, 5: 419-424.
17
Jahanbakhsh Z, Rasoulian B, Jafari M, Shekarforoush S, Esmailidehaj M, Mohammadi MT. et al. 2012. Protective effect of crocin against reperfusion-induced cardiac arrhythmiasin anaesthetized rats. EXCLI J, 11: 20-9.
18
Kuhlencordt PJ, Gyurko R, Han F, Scherrer-Crosbie M, Aretz TH, et al. 2001. Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double knockout mice. Circulation, 104: 448-454.
19
Lopaschuk GD, Barr R, Thomas PD, Dyck JR. 2003. Beneficial effects of Trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme A thiolase, Circ Res, 93: 33-37.
20
Ochiai T, Shimeno H, Mishima K, Iwasaki K, Fujiwara M, Tanaka H, et al. 2007. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochimica et biophysicaacta, 1770: 578-84.
21
Osada M, Netticadan T, Tamura K, Dhalla NS. 1998. Modification of ischemia–reperfusion induced changes in cardiac sarcoplasmic reticulum by preconditioning. Am J Physiol, 274: 2025- 2034.
22
Shaul PW. 2002. Regulation of endothelial nitric oxide synthase location. Annu Rev Physiol, 64: 749-774.
23
Srivastava S, Chandrasekar B, Gu Y, Luo J, Hamid T, Hill BG. 2007. Down regulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res. 74: 445-455.
24
Scherrer-Crosbie M, Ullrich R, Bloch KD, Nakajima H, Nasseri B, Aretz HT et al. 2001. Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice. Circulation, 104: 1286-1291.
25
Upaganlawar A and Balaraman R. 2010. Effect of vitamin E and green tea on hemodynamic, electro cardiographic and some biochemical alterations in experimentally induced myocardial infarction in rats. European Journal of Integrative Medicine, 2: 135-141.
26
Zhou B, Wu LM, Yang L, Liu ZL. 2005. Evidence for alpha-tocopherol regeneration reaction of green tea polyphenols in SDS micelles. Free radical biology & medicine, 38: 78-84.
27
ORIGINAL_ARTICLE
Saffron supplements modulate serum pro-oxidant-antioxidant balance in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial
Objectives: We have investigated the effect of a saffron supplement, given at a dose of 100 mg/kg, on prooxidant-antioxidant balance (PAB) in individuals with metabolic syndrome. Materials and Methods: A randomized, placebo-controlled trial design was used in 75 subjects with metabolic syndrome who were randomly allocated to one of two study groups: (1) the case group received 100mg/kg saffron and (2) the placebo control group received placebo for 12 weeks. The serum PAB assay was applied to all subjects before (week 0) and after (weeks 6 and 12) the intervention. Results: There was a significant (p=0.035) reduction in serum PAB between week 0 to week 6 and also from week 0 to week 12. Conclusion: Saffron supplements can modulate serum PAB in subjects with metabolic syndrome, implying an improvement in some aspects of oxidative stress or antioxidant protection.
https://ajp.mums.ac.ir/article_4672_f451efcf2aa534d165b0ab34d557ed0f.pdf
2015-09-01
427
433
10.22038/ajp.2015.4672
metabolic syndrome
Prooxidant-antioxidant balance
Saffron
Tayyebeh
Kermani
t. kermani@yahoo.com
1
Department of Anatomy and Cell biology, Birjand University of Medical Sciences, Birjand, Iran.
AUTHOR
Seyyed Hadi
Mousavi
mousavi@yahoo.com
2
Pharmacological Research Center of Medicinal Plant, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
AUTHOR
Maryam
Shemshian
shemshian@yahoo.com
3
Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
AUTHOR
Abdolreza
Norouzy
norouzy@yahoo.com
4
Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
AUTHOR
Mohsen
Mazidi
mazidim911@mums.ac.ir
5
Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, Beijing, China.
AUTHOR
Atefeh
Moezzi
moezzi@yahoo.com
6
Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
AUTHOR
Toktam
Moghiman
moghiman@yahoo.com
7
Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
AUTHOR
Majid
Ghayour-Mobarhan
mazidi_ns@yahoo.com
8
Cardiovascular Research Center, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
LEAD_AUTHOR
Gordon. A.
Ferns
ferns@yahoo.com
9
Division of Medical Education, Brighton & Sussex Medical School, Rm 342, Mayfield House, University of Brighton, BN1 9PH, United Kingdom
AUTHOR
Alamdari DH, Ghayour-Mobarhan M, Tavallaie S, Parizadeh MR, Moohebati M, Ghafoori F. 2008. Prooxidant-antioxidant balance as a new risk factor in patients with angiographically defined coronary artery disease. Clin Biochem ,41:375-380.
1
Abe K, Sugiura M, Yamaguchi S, Shoyama Y, Saito H. 1999. Saffron extract prevents acetaldehyde-induced inhibition of long-term potentiation in the rat dentate gyrus in vivo. Brain Res, 851:287-289.
2
Ahmad AS, Ansari MA, Ahmad M, Saleem S, Yousuf S, Hoda MN.2005. Neuroprotection by crocetin in a hemi-parkinsonian rat model. Pharmacol Biochem Behav, 81:805-813.
3
Bors W, Saran M, Michel C. 1982. Radical intermediates involved in the bleaching of the carotenoid crocin, Hydroxyl radicals, superoxide anions and hydrated electrons. Int J Radiat Biol Relat Stud Phys Chem Med, 41: 493- 501.
4
Eckel RH, Grundy SM, Zimmet PZ. 2005.The metabolic syndrome. Lancet, 365:1415-28.
5
Alberti KG, Zimmet P, Shaw J. 2006. Metabolic syndrome--a new world-wide definition. Diabet Med, 23: 469-480.
6
Edge R, McGarvey DJ, Truscott TG. 1997. The carotenoids as anti-oxidants-a review. J Photochem Photobiol B, 4: 189-200.
7
Falsoleiman H, Dehghani M, Moohebati M.. 2011. Changes in prooxidant- antioxidant balance after bare metal and drug eluting stent implantation in patients with stable coronary disease. Clin Biochem, 44: 160-164.
8
Gong W, Gottlieb S, Collins J, Blescia A, Dietz H, Goldmuntz E, McDonald-McGinn DM, Zackai EH, Emanuel BS, Driscoll DA, Budarf ML. 2001. Mutation analysis of TBX1 in non-deleted patients with features of DGS/VCFS or isolated cardiovascular defects. J Med Genet. , 38: E45.
9
Grundy SM. 2008. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol, 28: 629-636.
10
Hosseinzadeh H, Modaghegh MH, Saffari Z. 2009. Crocus sativus L. (Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid Based Complement Alternat Med, 6: 343-350.
11
He S-Y, Qian Z-Y, Wen N, Tang F-T, Xu G-L, Zhou C-H. 2007. Influence of Crocetin on experimental atherosclerosis in hyperlipidamic-diet quails. Eur J Pharmacol, 554: 191-195.
12
He S-Y, Qian Z-Y, Tang F-T, Wen N, Xu G-L, Sheng L. 2005. Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci, 77: 907-921.
13
Kaminski KA, Bonda TA, Korecki J, Musial WJ. 2002. Oxidative stress and neutrophil activation--the two keystones of ischemia/reperfusion injury. Int J Cardiol, 86: 41-59.
14
Kotur-Stevuljevic J, Memon L, Stefanovic A, Spasic S, Spasojevic-Kalimanovska V, Bogavac-Stanojevic N. 2007. Correlation of oxidative stress parameters and inflammatory markers in coronary artery disease patients.Clin Biochem, 40: 181-187.
15
Lafont AM, Chai YC, Cornhill JF, Whitlow PL, Howe PH, Chisolm GM. 1995. Effect of alpha-tocopherol on restenosis after angioplasty in a model of experimental atherosclerosis.J Clin Invest, 95: 1018-1025.
16
Nair SC, Salomi MJ, Varghese CD, Panikkar B, Panikkar KR. 1992. Effect of saffron on thymocyte proliferation, intracellular glutathione levels and its antitumor activity. Biofactors, 4: 51-54.
17
Nair SC, Pannikar B, Panikkar KR. 1991.Antitumour activity of saffron (Crocus sativus). Cancer Lett, 57: 109-1014.
18
Nesto RW. 2003. The relation of insulin resistance syndromes to risk of cardiovascular disease. Rev Cardiovas Med, 4: S11.
19
Nunes GL, Sgoutas DS, Redden RA, Sigman SR, Gravanis MB, King SB, III. 1995. Combination of vitamins C and E alters the response to coronary balloon injury in the pig. Arterioscler Thromb Vasc Biol, 15: 156-65.
20
Papandreou MA, Tsachaki M, Efthimiopoulos S, Cordopatis P, Lamari FN, Margarity M. 2011 .Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection. Behav Brain Res, 219 : 197-204.
21
Palozza P, Krinsky NI. 1992. Antioxidant effects of carotenoids in vivo and in vitro: an overview. Methods Enzymol, 213: 403-420.
22
Rahsepar AA, Mirzaee A, Moodi F, Moohebati M, Tavallaie S, Eshraghi A. 2012. Anti-Heat Shock Protein 27 Titers and Oxidative Stress Levels are Elevated in Patients WithValvular Heart Disease. Angiology, 63: 609-16.
23
Rı´os JL, RecioMC, Giner RM, Ma´nˇ ezS. 1996. An update review of saffron and its active constituents. Phtother Res, 10 : 189-193.
24
Sadeghnia HR, Kamkar M, Assadpour E, Boroushaki MT, Ghorbani A. 2013. Protective effect of safranal, a constituent of Crocus sativus, on quinolinic acid-induced oxidative damage in rat hippocampus. Iran J Basic Med Sci; 16: 73-82.
25
Tardif JC, Cote G, Lesperance J, Bourassa M, Lambert J, Doucet S. 1997. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Multivitamins and Probucol Study Group. N Engl J Med, 337: 365-72.
26
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27
Walter MF, Jacob RF, Jeffers B, Ghadanfar MM, Preston GM, Buch J. 2004. Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study. J Am Coll Cardiol, 44: 1996-2002.
28
Yoshino F, Yoshida A, Umigai N, Kubo K, Lee MC. 2011.Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain. J Clin Biochem Nutr, 49 : 182-7.
29
Zhang Y, Shoyama Y, Sugiura M, Saito H. Effects of Crocus sativus L. 1994.On the ethanol-induced impairment of passive avoidance performances in mice. Biol Pharm Bull, 17: 217-221.
30
ORIGINAL_ARTICLE
Effect of saffron on liver metastases in patients suffering from cancers with liver metastases: A randomized, double blind, placebo-controlled clinical trial
Objective: Cancer represents the second cause of mortality in the world. Saffron as a medicinal plant is known for its anti-cancer and anti-depressant properties. In this randomized double blind clinical trial, the effects of saffron on response to treatment in patients suffering from liver metastasis were evaluated. Materials and Methods: Thirteen patients suffering from liver metastases who referred to Ghaem and Imam Reza hospital, Mashhad, Iran were included in this study and then divided into two different groups. Both groups received chemotherapy regimen. Patients in group one were treated with saffron capsule (50 mg, twice daily) during chemotherapy periods whereas patients in group two received placebo. A sum of the longest diameter were calculated and compared for all lesions in IV contrast CT scan before and after the treatment. Results: from 13 patients included in this study, six patients quit and seven continued until the end. In saffron-treated group, two patients showed partial and complete response (50%) whereas in placebo group, no response was seen. Also, two deaths in placebo and one in saffron group occurred. Conclusion: This research suggests that saffron might be useful in patients suffering from liver metastasis. However, further investigations with larger sample size are required.
https://ajp.mums.ac.ir/article_4667_a0fdf5b066a0beb302df9a0c5ea98136.pdf
2015-09-01
434
440
10.22038/ajp.2015.4667
Saffron
Cancer
Liver Metastases
Azar
Hosseini
hoseiniaz@mums.ac.ir
1
Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Seyed Hamed
Mousavi
ssmousavi@yahoo.com
2
Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Anis
Ghanbari
anisghanbari62@yahoo.com
3
Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Fatemeh
Homaei-Shandiz
homaeif@yahoo.com
4
Department of Oncology, Omid Hospitsal, Mashhad, Iran.
AUTHOR
Hamid-Reza
Raziee
razieehr@yahoo.com
5
Department of Oncology, Omid Hospitsal, Mashhad, Iran.
AUTHOR
Masoud
Pezeshki-Rad
pezeshkiradm@mums.ac.ir
6
Department of Oncology, Emam Reza Hospitsal, Mashhad, Iran.
AUTHOR
Seyed Hadi
Mousavi
mousavih@mums.ac.ir
7
Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
LEAD_AUTHOR
Abdullaev FI, Frenkel GD. 1992. The Effect of Saffron on Intracellular DNA, RNA and Protein Synthesis in Malignant and Non-malignant Human Cells. Biofactors, 4: 43–5.
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3
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García-Olmo DC1, Riese HH, Escribano J, Ontañón J, Fernandez JA, Atiénzar M, García-Olmo D. 1999. Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. Nutr Cancer, 35 :120-126.
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Hosseinzadeh H, Sadeghnia HR. 2007. Effect of Safranal, A Constituent of Crocus sativus (Saffron), on Methyl Methanesulfonate (MMS)-Induced DNA Damage in Mouse Organs: An Alkaline Single-Cell Gel Electrophoresis (Comet) Assay. DNA Cell Biol, 26: 841-6.
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27
Magesh V, Singh JP, Selvendiran K, Ekambaram G, Sakthisekaran D. 2006. Antitumour Activity of Crocetin in Accordance to Tumor Incidence, Antioxidant Status, Drug Metabolizing Enzymes and Histopathological Studies. Mol Cell Biochem, 287: 127–35.
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Martin G, Goh E, Neff AW.2002. Evaluation of the developmental toxicity of crocetin on Xenopus. Food Chem Toxicol, 40: 959-964.
29
Moln´ar J, Kars MD, Gunduz U. 2009. Interaction of tomato lectin with ABC transporter in cancer cells: glycosylation confers functional conformation of P-gp. Acta Histochemica, 111: 329–333.
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Mousavi SH, Moallem SA, Mehri S, Shahsavand S, Nassirli H, Malaekeh-Nikouei B. 2011. Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form. Pharm Biol, 49: 1039-1045.
31
Mousavi SH, Tavakkol-Afshari J, Brook A, Anarkooli Jafari I. 2009. Role of caspases and Bax protein in saffron-induced apoptosis in MCF-7 cells. Food Chem Toxicol, 47: 1909–1913.
32
Nair SC, Pannikar B, Panikkar KR. 1991. Antitumour activity of saffron (Crocus sativus). Cancer Lett, 57: 109–114.
33
Nair SC.1991. Antitumor activity of saffron (Crocus sativus). Cancer Lett. 57: 109-114.
34
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Premkumar K, Abraham SK, Santhiya ST, Ramesh A. 2003. Protective effects of saffron( Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice, Phytother Res, 17: 614–617.
37
Salomi MJ, Nair SC, Panikkar KR. 1991. Inhibitory Effects of Nigella sativa and Saffron (Crocus sativus) on Chemical Carcinogenesis in Mice. Nutr Cancer,16: 67–82.
38
Schmidt M, Betti G, Hensel A. 2007. Saffron in Phytotherapy: Pharmacology and Clinical Uses. Wien Med Wochenschr, 157:315-319.
39
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40
Tanaka T, Shnimizu M. 2012. Cancer chemoprevention by carotenoids. Molecules, 17: 3202–3242.
41
Tavakkol-Afshari J, Brook A, Mousavi SH. 2008. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem Toxicol 46: 3443–3447.
42
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43
ORIGINAL_ARTICLE
Safranal as a safe compound to mice immune system
Objectives: The aim of the present study was to investigate immunotoxic effect of safranal (SAF), a main component of Crocus sativus essential oil, using Balb/c mice. Materials and Methods: SAF was administered intraperitoneally at doses of 0.1, 0.5 and 1 ml/kg for 3 weeks. Hystopathological examination of spleen and bone marrow, cellularity of spleen, delayed type of hypersensitivity (DTH) response, hemagglutination titer (HA), cytokine production and lymphocyte proliferation assay were studied in various groups of animals. Results: Spleen cellularity for SAF groups (0.1 ml/kg SAF: 6.68 [± 0.88] × 107, 0.5 ml/kg SAF: 8.16 [± 1.33] × 107, 1 ml/kg SAF: 6.12 [± 0.59] × 107) did not significantly differ as compared to vehicle control (8.52 [± 1.36] × 107; p > 0.05). In addition, SAF at all doses could not produce any significant changes in hematological parameters, HA titer, DTH and lymphoproliferation responses, as well as in release of cytokines by isolated splenocytes (p > 0.05). Despite a few studies demonstrating some immunomodulatory effects for saffron extract, SAF as a major constituent of saffron did not induce any marked effects in immune system parameters of mice. Conclusion: Contrary to the toxicological studies which have indicated that SAF is more toxic than other active constituents in saffron stigma, at least it was found to be safe to mice immune system and has no toxicity on humoral and cellular immune responses.
https://ajp.mums.ac.ir/article_4504_ffa1d7cbb9e1401c0c47f4000c41f108.pdf
2015-09-01
441
449
10.22038/ajp.2015.4504
Safranal
Immunotoxic effect
Cellular immunity
Humoral immunity
Bamdad
Riahi-Zanjani
riahib@mums.ac.ir
1
Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mahdi
Balali-Mood
balalimoodm@mums.ac.ir
2
Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Elaheh
Mohammadi
mohammadie911@mums.ac.ir
3
Medical Toxicology Research Center and Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Hassan
Badie-Bostan
badieh931@mums.ac.ir
4
Medical Toxicology Research Center and Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Bahram
Memar
memarb@mums.ac.ir
5
Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Gholamreza
Karimi
karimig@mums.ac.ir
6
Medical Toxicology Research Center and Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Abdullaev FI, Riveron NL, Caballero-Ortegaa H, Manuel Hernandez J, Perez-Lopez I, Pereda-Miranda R, Espinosa-Aguirre JJ. 2003. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol Invitro, 17: 731–736.
1
Assimopoulou AN, Sinakosa Z, Papageorgiou VP. 2005. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res, 19: 997-1000.
2
Bendich, A. 1993. Physiological role of antioxidants in the immune system. J Dairy Sci, 76: 2789-2794.
3
Boskabady MH, Aslani MR. 2006. Relaxant effect of Crocus sativus(saffron) on guinea-pig tracheal chains and its possible mechanisms. J Pharm Pharmacol, 58: 1385-1390.
4
Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A. 2011. The effect of Crocus sativus extract on human lymphocytes' cytokines and T helper 2/T helper 1 balance. J Med Food, 14: 1538-1545.
5
Boskabady MH, Byrami G, Feizpour A. 2014. The effect of safranal, a constituent of Crocus sativus (saffron), on tracheal responsiveness, serum levels of cytokines, total NO and nitrite in sensitized guinea pigs. Pharmacol Rep, 66: 56-61.
6
De La Fuente M, Victor VM. 2000. Anti-oxidants as modulators of immune function. Immunol Cell Biol, 78: 49-54.
7
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9
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12
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22
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29
ORIGINAL_ARTICLE
Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats
Objectives: Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. Materials and Methods: A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Results: Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. Conclusion: The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.
https://ajp.mums.ac.ir/article_4547_7331a79e51fccf9e1d54be72802c8754.pdf
2015-09-01
450
457
10.22038/ajp.2015.4547
Crocin
Morphine
Naloxone
Orofacial pain
Rats
Esmaeal
Tamaddonfard
e_tamaddonfard@yahoo.com
1
Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
LEAD_AUTHOR
Sina
Tamaddonfard
tamaddonfards@yahoo.com
2
Faculty of Veterinary Medicine, Urmia Azad University, Urmia, I.R. Iran
AUTHOR
Salar
Pourbaba
pourbabas@yahoo.com
3
Faculty of Veterinary Medicine, Urmia Azad University, Urmia, I.R. Iran
AUTHOR
Alavizadeh SH, Hosseinzadeh H. 2014. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food ChemToxicol, 64: 65-80.
1
Arendt-Nielsen L, Svenson P, Sessle BJ, Cairns BE, Wang K. 2008. Interactions between glutamate and capsaicin in inducing muscle pain and sensitization in humans. Eur J Pain, 12: 661-670.
2
Asri-Rezaei S, Tamaddonfard E, Ghasemsoltani-Momtaz B, Erfanparast A, Gholamalipour S. 2015. Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats. Avicenna J Phytomed, 5: Article in Press.
3
Aung HH, Wang CZ, Ni M, Fishbain A, Mehendale SR, Xie JT, Shoyama CY, Yuan CS. 2007. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol, 29: 175-180.
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Duale C, Luccarini P, Cadet R, Woda A. 1996. Effects of morphine microinjections into the trigeminal sensory complex on the formalin test in rats. Exp Neurol, 142: 331-339.
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Holanda Pinto SA, Pinto LM, Guedes MA, Cunha GM, Chaves MH, Santos FA, Rao VS. 2008. Antinociceptive effect of triterpenoid alpha, beta-amyrin in rats on orofacial pain induced by formalin and capsaicin. Phytomedicine, 15: 630-634.
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Karami M, Bathaie SZ, Tiraihi T, Habbibi-Rezaei M, Arabkheradmand J, Faghihzadeh S. 2013. Crocin improved locomotor function and mechanical behavior in a rat model of contused spinal cord injury through decreasing calcitonic gene related peptide (CGRP). Phytomedicine, 21: 62-67.
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Lee IA, Lee JH, Baek NI, Kim DH. 2005. Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite crocetin. Biol Pharm Bull, 28: 2106-2110.
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Quintans-Junior LJ, Melo MS, De Sausa DP, Araujo AA, Onofre AC, Gelain DP, Goncalves JC, Araujo DA, Almeida JR, Bonjardim LR. 2010. Antinociceptive effect of citronellal in formalin-, capsaicin-, and glutamate-induced orofacial nociception in rodents and its action on nerve excitability. J Orofac Pain, 24: 305-312.
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26
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27
Tamaddonfard E, Erfanparast A, Taati M, Dabbaghi M. 2014. Role of opioid system in verapamil-induced antinociception in a rat model of orofacial pain. Res Vet Forum, 5: 49-54.
28
Tamaddonfard E, Farshid AA, Ahmadian E, Hamidhoseyni A. 2013a. Crocin enhanced functional recovery after sciatic nerve crush injury in rats. Iran J Basic Med Sci, 16: 83-90.
29
Tamaddonfard E, Farshid AA, Eghdami K, Samadi F, Erfanparast A. 2013b. Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats. Pharmacol Rep, 65: 1272-1280.
30
Tamaddonfard E, Hamzeh-Gooshchi N. 2010a. Effect of crocin on the morphine-induced antinociception in the formalin test in rats. Phytother Res, 24: 410-413.
31
Tamaddonfard E, Hamzeh-Gooshchi N. 2010b. Effect of intraperitoneal and intracerebroventricular injection of crocin on acute corneal pain in rats. Phytother Res, 24: 1463-1467.
32
Tamaddonfard E, Hamzeh-Gooshchi N, Seiednejad-Yamchi S. 2012.Central effect of crocin on penicillin-induced epileptiform activity in rats.Pharmacol Rep, 64: 94-101.
33
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34
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35
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36
ORIGINAL_ARTICLE
Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice
Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.
https://ajp.mums.ac.ir/article_4619_662ae1aae4c0fe4049b5eb18546160d5.pdf
2015-09-01
458
468
10.22038/ajp.2015.4619
Crocus sativus L
Crocetin
Crocin
Forced swimming test (FST)
Tail suspension test (TST)
Bahareh
Amin
amin.bahareh@gmail.com
1
Department of Pharmacology and Physiology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
AUTHOR
Alireza
Nakhsaz
2
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad Iran
AUTHOR
Hossein
Hosseinzadeh
hosseinzadehh@mums.ac.ir
3
Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Abdullaev F. 1993. Biological effects of saffron. Bio Factors, 4:83-86.
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2
Asai A, Nakano T, Takahashi M, Nagao A. 2005. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J Agric Food Chem, 53:7302-7306.
3
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17
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23
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Schulz V. 2006. Safety of St. John's Wort extract compared to synthetic antidepressants. Phytomedicine, 13:199-204.
37
Shirali S, Zahra Bathaie S, Nakhjavani M. 2013. Effect of crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats. Phytother Res, 27:1042-1047.
38
Szafrański T. 2014. Herbal remedies in depression-state of the art. Psychiatr Pol, 48:59-73.
39
Xi L, Qian Z, Du P, Fu J. 2007.Pharmacokinetic properties of crocin (crocetindigentiobiose ester) following oral administration in rats. Phytomedicine, 14:633-636.
40
Talaei A, Hassanpour Moghadam M, SajadiTabassi SA, Mohajeri SA. 2013. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. J Affect Disord, 174: 51-56.
41
Yoshino F, Yoshida A, Umigai N, Kubo K, Lee MC. 2011. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain. J Clin Biochem Nutr, 49:182-187
42
Zargari A. 1990. Medicinal plants, pp. 574-578, Tehran, University Press.
43
ORIGINAL_ARTICLE
Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats
Objectives: Crocin and safranal, the major constituents of saffron, exert neuroprotective effects. In the present study, we investigated the effects of crocin and safranal (alone or in combination with insulin) on peripheral neuropathy in diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (i.p.) injection of 60 mg/kg of streptozotocin (STZ) and confirmed by blood glucose level higher than 250 mg/dl. After confirmation of diabetes, crocin (30 mg/kg, i.p.), safranal (1 mg/kg, i.p.) (alone or in combination with insulin) and insulin (5 IU/kg, s.c.) were administered for eight weeks. Neuropathic pain was evaluated using acetone drop test. Histopathological changes of sciatic nerve were evaluated using light microscope. Blood glucose levels and sciatic nerve malondialdehyde (MDA) contents were also measured. Results: STZ caused cold allodynia, edema and degenerative changes of sciatic nerve, hyperglycemia and an elevation of sciatic nerve MDA levels. Crocin, safranal and insulin improved STZ-induced behavioral, histopathological and biochemical changes. Combined treatments produced more documented improving effects. Conclusion: The results of the present study showed neuroprotective effects of crocin, safranal and insulin in a rat model of diabetic neuropathy. In addition, crocin and safranal enhanced the neuroprotective effect of insulin. The neuroprotective effects of theses chemical compounds could be associated with their anti-hyperglycemic and antioxidant properties.
https://ajp.mums.ac.ir/article_4666_57849ea4a1ed2e2c6496ffe64d972139.pdf
2015-09-01
469
478
10.22038/ajp.2015.4666
Crocin
Safranal
Insulin
Diabetic neuropathy
Rats
Amir
Farshid
aa.farshid@urmia.ac.ir
1
Division of Pathology, Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
LEAD_AUTHOR
Esmaeal
Tamaddonfard
etamaddonfard@yahoo.com
2
Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran
AUTHOR
Alinejad B, Ghorbani A, Sadeghnia HR. 2013. Effects of combination of curcumin, linalool, rutin, safranal, and thymoquinone on glucose/serum deprivation-induced cell death. Avicenna J Phytomed, 3: 321-328.
1
Altinoz E, Oner Z, Elbe H, Cigremis Y, Turkoz Y. 2015. Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats. Hum Exp Toxicol, 34: 127-134.
2
Asri-Rezaei S, tamaddonfard E, Ghasemsoltani-Momtaz B, Erfanparast A, Gholamalipour S. 2015. Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats. Avicenna J Phytomed, 5: Article in Press.
3
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