Browse > Article
http://dx.doi.org/10.3831/KPI.2018.21.031

The Prophylactic and Therapeutic Effects of Saffron Extract and Crocin on Ethanol Withdrawal Syndrome in Mice  

Shoja, Maryam (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences)
Mehri, Soghra (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences)
Amin, Bahareh (Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences)
Askari, Vahid Reza (Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences)
Hosseinzadeh, Hossein (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences)
Publication Information
Journal of Pharmacopuncture / v.21, no.4, 2018 , pp. 277-283 More about this Journal
Abstract
Objectives: Ethanol withdrawal following its chronic use is a serious outcome and challenging to treatment. The chronic use of ethanol induces a progressive neuroplasticity in different reigns of brain. In this study we evaluated the effects of aqueous extract of Crocus sativus L. (saffron) and its active compound, crocin, on the withdrawal behavior induced after repeated administration of ethanol, in two regimens of prophylactic (administration of drugs concomitant with the induction of dependence) and treatment (administration of drugs during the period of ethanol withdrawal) in mice which received ethanol. Methods: Ethanol dependence was induced by oral administration of 10% v/v ethanol (2 g/kg) for 7 days. The aqueous extracts of saffron (40, 80 and 160) and crocin (10, 20 and 40 mg/kg) were administered to mice in two regimens of prophylactic (along with ethanol) and treatment (during withdrawal period). Diazepam (1 mg/kg) was used as a positive control. Six hours after discontinuation of the ethanol, seizure was evaluated by the sub-convulsive dose of pentyleneltetrazole (PTZ) (30 mg/kg). The open field test and Rota rod test were used for evaluation of locomotor activity and motor incoordination, respectively. Results: Both extracts and crocin increased the number of crossed lined in the open field test. PTZ kindling seizure was inhibited in animals received extract (80 and 160 mg/kg) in both regimens. Motor incoordination was only improved following administration of crocin. Conclusion: The aqueous extract of saffron and crocin can be considered as safe agents and reliable alternative to diazepam in management of ethanol withdrawal syndrome.
Keywords
alcohol withdrawal; pentylenetetrazol; Crocus sativus; crocin; open field test;
Citations & Related Records
연도 인용수 순위
  • Reference
1 McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R. The use of behavioral test batteries: effects of training history. Physiolo Behav. 2001;73(5):705-717.   DOI
2 Knapp DJ, Breese GR. Models of chronic alcohol exposure and dependence. Psychiatric Disorders: Methods Protoc. 2012;205-230.
3 Uzbay IT, Usanmaz SE, Tapanyigit EE, Aynacioglu S, Akarsu ES. Dopaminergic and serotonergic alterations in the rat brain during ethanol withdrawal: association with behavioral signs. Drug Alcohol Depend. 1998;53(1):39-47.   DOI
4 Treit D, Engin E, McEown K. Animal models of anxiety and anxiolytic drug action. Curr Top Behav Neurosci. 2010;2:121-60.
5 Kyzar EJ, Pandey SC. Molecular mechanisms of synaptic remodeling in alcoholism. Neurosci Lett. 2015;601:11-19.   DOI
6 Berger F, Hensel A, Nieber K. Saffron extract and trans-crocetin inhibit glutamatergic synaptic transmission in rat cortical brain slices. Neuroscience. 2011;180:238-247.   DOI
7 Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia. 2005;76(7):722-724.   DOI
8 Sadeghnia HR, Cortez MA, Liu D, Hosseinzadeh H, Snead OC. Antiabsence effects of safranal in acute experimental seizure models: EEG and autoradiography. J Pharm Pharm Sci. 2008;11(3):1-14.
9 Rios JL, Recio MC, Giner RM, Manez S. An update review of saffron and its active constituents. Phytother Res. 1996;10(3):189-193.   DOI
10 Abe K, Sugiura M, Shoyama Y, Saito H. Crocin antagonizes ethanol inhibition of NMDA receptor-mediated responses in rat hippocampal neurons. Brain Res. 1998;787(1):132-138.   DOI
11 Razavi M, Hosseinzadeh H, Abnous K, Motamedshariaty VS, Imenshahidi M. Crocin restores hypotensive effect of subchronic administration of diazinon in rats. Iran J Basic Med Sci. 2013;16(1):64-72.
12 Mehdizadeh R, Parizadeh MR, Khooei AR, Mehri S, Hosseinzadeh H. Cardioprotective Effect of Saffron Extract and Safranal in Isoproterenol-Induced Myocardial Infarction in Wistar Rats. Iran J Basic Med Sci. 2013;16(1):56-63.
13 Lari P, Abnous K, Imenshahidi M. Evaluation of diazinon-induced hepatotoxicity and protective effects of crocin. Toxicol Ind Health. 2013;31(4):367-376.   DOI
14 Hassani FV, Mehri S, Abnous K, Birner-Gruenberger R, Hosseinzadeh H. Protective effect of crocin on BPA-induced liver toxicity in rats through inhibition of oxidative stress and downregulation of MAPK and MAPKAP signaling pathway and miRNA-122 expression. Food Chem Toxicol. 2017;107:395-405.   DOI
15 Yousefsani BS, Pourahmad J, Hosseinzadeh H. The mechanism of protective effect of crocin against liver mitochondrial toxicity caused by arsenic III. Toxicol Mech Meth. 2018;28(2):105-114.   DOI
16 Mohammadzadeh L, Hosseinzadeh H, Abnous K, Razavi BM. Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats. Environ Sci Pollut Res Int. 2018;25(5):4904-4914.   DOI
17 Heidari S, Mehri S, Hosseinzadeh H. Memory enhancement and protective effects of crocin against D-galactose aging model in the hippocampus of Wistar rats. Iran J Basic Med Sci. 2017;20(11):1250-1259.
18 Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2002;2:1-8.
19 Rameshrad M, Razavi BM, Hosseinzadeh H. Saffron and its derivatives, crocin, crocetin and safranal: a patent review. Expert Opin Ther Pate. 2017;1-19.
20 Amin B, Hosseinzadeh H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia. 2012;83(5):888-895.   DOI
21 Rastgoo M, Hosseinzadeh H, Alavizadeh H, Abbasi A, Ayati Z, Jaafari MR. Antitumor Activity of PEGylated Nanoliposomes Containing Crocin in Mice Bearing C26 Colon Carcinoma. Planta Med. 2013;79(06):447-451.   DOI
22 Khorasany A, Hosseinzadeh H. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review. Iran J Basic Med Sci. 2016;19(5):455-469.
23 Shamsa A, Hosseinzadeh H, Molaei M, Shakeri MT, Rajabi O. Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: A pilot study. Phytomedicine. 2009;16(8):690-693.   DOI
24 Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O, Hosseinzadeh H. Safety Evaluation of Crocin (a constituent of saffron) Tablets in Healthy Volunteers. Iran J Basic Med Sci. 2013;16(1):39-46.
25 Smith-Alnimer M, Watford MF. Alcohol Withdrawal and Delirium Tremens: Fast recognition may save a patient from the worst of withdrawal. Am J Nurs. 2004;104(5):72-75.   DOI
26 Bostan H, Mehri S, Hosseinzadeh H. Toxicology effects of saffron and its constituents: a review. Iran J Basic Med Sci. 2017;20(2):110-121.
27 Moshiri M, Vahabzadeh M, Hosseinzadeh H. Clinical Applications of Saffron (Crocus sativus) and its Constituents: A Review. Drug Res. 2015;65(06):287-295.
28 Razavi BM, Hosseinzadeh H. Saffron: a promising natural medicine in the treatment of metabolic syndrome. J Sci Food Agric. 2017;97(6):1679-1685.   DOI
29 Koob GF. Addiction is a reward deficit and stress surfeit disorder. Front Psychiatry. 2013;4:72.
30 Rahman S, Engleman EA, Bell RL. Nicotinic receptor modulation to treat alcohol and drug dependence. Front Neurosci. 2015;8:426.
31 Bayard M, McIntyre J, Hill KR, Woodside J. Alcohol Withdrawal Syndrome. Am Fam Physician. 2004;69(6):1443-1450.
32 Ennaceur A, Michalikova S, van Rensburg R, Chazot PL. Tolerance, sensitization and dependence to diazepam in Balb/c mice exposed to a novel open space anxiety test. Behav Brain Res. 2010;209(1):154-164.   DOI
33 Mollazadeh H, Emami SA, Hosseinzadeh H. Razi's Al-Hawi and saffron (Crocus sativus): a review. Iran J Basic Med Sci. 2015;18(12):1153-1166.
34 Hosseinzadeh H, Khosravan V. Anticonvulsant effects of aqueous and ethanolic extracts of Crocus sativus L. stigmas in mice. Arc Iran Medi. 2002;5:44-47.
35 Ettehadi H, Mojabi SN, Ranjbaran M, Shams J, Sahraei H, Hedayati M, et al. Aqueous Extract of Saffron (Crocus sativus) Increases Brain Dopamine and Glutamate Concentrations in Rats. J Behav Brain Sci. 2013;3:315-319.   DOI
36 Nassiri-Asl M, Hosseinzadeh H. Chapter 3 - Neuropharmacology Effects of Saffron (Crocus sativus) and Its Active Constituents A2 - Watson, Ronald Ross, in Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease, V.R. Preedy, Editor. 2015;Academic Press:San Diego.29-39.
37 Hosseinzadeh H, Karimi G, Niapoor M. Antidepressant effect of Crocus sativus L. stigma extracts and their constituents, crocin and safranal, in mice. J Med Plants. 2004;3(11):48-58.
38 Amin B, Malekzadeh M, Heidari MR, Hosseinzadeh H. Effect of Crocus sativus extracts and its active constituent safranal on the harmaline-induced tremor in mice. Iran J Basic Med Sci. 2015;18(5):449-458.
39 Hosseinzadeh H, Nassiri-Asl M. Avicenna's (Ibn Sina) the Canon of Medicine and Saffron (Crocus sativus): A Review. Phytother Res. 2013;27(4):475-483.   DOI
40 Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem Toxicol. 2014;64:65-80.   DOI
41 Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, et al. 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. 2011;667(1):222-229.   DOI
42 Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res. 2009;23(6):768-774.   DOI
43 Hosseinzadeh H, Jahanian Z. Effect of crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice. Phytother Res. 2010;24(5):726-730.   DOI
44 Pardon MC, Perez-Diaz F, Joubert C, Cohen-Salmon C. Age-dependent effects of a chronic ultramild stress procedure on open-field behaviour in B6D2F1 female mice. Physiol Behav. 2000;70(1):7-13.   DOI
45 Hadizadeh F, Mohajeri S, Seifi M. Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method. Pak J Biol Sci. 2010;13:691-698.   DOI
46 Ruby B, Benson MK, Kumar EP, Sudha S, Wilking JE. Evaluation of Ashwagandha in alcohol withdrawal syndrome. Asian Pac J Trop Dis. 2012;2:856-860.   DOI
47 Hassani FV, Naseri V, Razavi BM, Mehri S, Abnous K, Hosseinzadeh H. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. Daru. 2014;22:1-9.   DOI