Investigating the effect of hydro-alcoholic extract of Salix aegyptiaca on anxiety in male rat


1 Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

2 Department of Physiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran


Background: Anxiety disorders are frequently common neuropsychiatric disorders. Herbal medicines are widespread and used universal as a treatment compound for anxiety. The present study investigated the effects of hydro-alcoholic extract of Salix aegyptiaca blossom on rat behavior in the elevated plus-maze (EPM) and compared results with the effects of diazepam, as a positive control drug.
Materials and Methods: Seventy adult male Wistar rats were divided into seven groups (N = 10). Animals received S. aegyptiaca extract (25, 50, 100 mg/kg) or Diazepam (0.3, 0.6, or 1.2 mg/kg) intraperitoneally and the control group was given the vehicle (10 ml/kg) 30 min before submitting into plus-maze test. The number of entries into the open and closed arms, the percentage of entries into the open arms of the EPM, and the time spent in the open arms were recorded.
Results: The results revealed significant increases in percentage of entries into the open arms (P < 0.01) and in the time spent in the open arms (P < 0.01) after administration of diazepam (0.3, 0.6) and S. aegyptiaca (50, 100 mg/kg) in compare with control group. S. aegyptiaca extract has no effects on the total distance covered by animals and number of closed arms entries, whereas diazepam decreased these parameters. The locomotor activity was not significantly changed by S. aegyptiaca.
Conclusion: Single-session administration of optimum doses of total extract of S. aegyptiaca has anxiolytic effects in rat similar to the low dose of diazepam. More research is needed for better understanding of anxiolytic properties and neurobiological mechanisms of action and probable interactions of S. aegyptiaca extract with neurotransmitters.


Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990–1997: Results of a follow-up national survey. JAMA 1998;280:1569-75.  Back to cited text no. 1
Lader MH. Limitations on the use of benzodiazepines in anxiety and insomnia: Are they justified? Eur Neuropsychopharmacol 1999;9:399-405.  Back to cited text no. 2
Lader M, Morton S. Benzodiazepine problems. Br J Addict 1991;86:823-8.  Back to cited text no. 3
Griffiths RR, Ator NA, Roache JD, Lamb RJ. Abuse liability of triazolam: Experimental measurements in animals and humans. Psychopharmacol Ser 1987;3:83-7.  Back to cited text no. 4
Holm M. One year follow-up of users of benzodiazepines in general practice. Dan Med Bull 1990;37:188-91.  Back to cited text no. 5
Zargari A. Medicinal Plants. 1st ed, Vol. 3. Tehran, Iran: Tehran University Press; 1990. p. 355-61.  Back to cited text no. 6
Ave-Sina A. Law in Medicine. Tehran, Iran; Bermejo Benito: Soroosh Press; 1988.  Back to cited text no. 7
Aqili Khorasani MH. Collection of Drugs (Materia Media). Tehran, Iran: Enqelab-e-Eslami Publishing and Educational Organization; 1991. p. 388-9.  Back to cited text no. 8
Sonboli A, Mojarrad M, Nejad Ebrahimi S, Enayat S. Free radical scavenging activity and total phenolic content of methanolic extracts from male inflorescence of Salix aegyptiaca grown in Iran. Iran J Pharm Res 2010;9:293-6.  Back to cited text no. 9
Karimi I, Hayatgheybi H, Shamspur T, Kamalak A, Pooyanmehr M, Marandi Y. Chemical composition and effect of an essential oil of Salix aegyptiaca (musk willow) in hypercholesterolemic rabbit model. Braz J Pharmacog 2011;21:407-14.  Back to cited text no. 10
Stephens DN, Andrews JS. Screening for anxiolytic drugs. In: Willner P, ed. Behavioural Models in Psychopharmacology: Theoretical, Industrial and Clinical Perspectives. Cambridge: Cambridge University Press; 1991.  Back to cited text no. 11
Barrett JE. Animal behavior models in the analysis and understanding of anxiolytic drugs acting at serotonin receptors. In: Olivier B, Mos J, Slangen JL, editors. Animal models in psychopharmacology. Switzerland: Basel Birkhauser Verlag; 1991. p. 37-52.  Back to cited text no. 12
Carobrez AP, Bertoglio LJ. Ethological and temporal analyses of anxiety like behavior: The elevated plus-maze model 20 years on. Neurosci Biobehav Rev 2005;29:1193-205.  Back to cited text no. 13
Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 1987;92:180-5.  Back to cited text no. 14
Pellow S, Chopin P, File SE, Briley M. Validation of open: Closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985;14:149-67.  Back to cited text no. 15
Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat. Pharmacol Biochem Behav 1986;24:526-30.  Back to cited text no. 16
Burghardt PR, Wilson MA. Microinjection of naltrexone into the central, but not the basolateral, amygdala blocks the anxiolytic effects of diazepam in the plus maze. Neuropsychopharmacology 2006;31:1227-40.  Back to cited text no. 17
Yildiz Akar F, Ulak G, Tanyeri P, Erden F, Utkan T, Gacar N. 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats. Pharmacol Biochem Behav 2007;87:434-43.  Back to cited text no. 18
Bacchi F, Mathé AA, Jiménez P, Stasi L, Arban R, Gerrard P, et al. Anxiolytic-like effect of the selective neuropeptide Y Y2 receptor antagonist BIIE0246 in the elevated plus-maze. Peptides 2006;27:3202-7.  Back to cited text no. 19
Drapier D, Bentué-Ferrer D, Laviolle B, Millet B, Allain H, Bourin M, et al. Effects of acute fluoxetine, paroxetine and desipramine on rats tested on the elevated plus-maze. Behav Brain Res 2007;176:202-9.  Back to cited text no. 20
Enayat S, Banerjee S. Comparative antioxidant activity of extracts from leaves, bark and catkins of Salix aegyptiaca. Food Chem 2009;116:23-8.  Back to cited text no. 21
Karawya MS, Ammar MN, Hifnawy MS, Al-Okbi SY, Mohamed DA, El- Anssary AA. Phytochemical study and evaluation of the anti-inflammatory activity of some medicinal plants growing in Egypt. Med J Islamic World Acad Sci 2010;18:139-50.  Back to cited text no. 22
Rabbani M, Sajjadi SE, Rahimi F. Anxiolytic effect of flowers of Salix aegyptiaca L. in mouse model of anxiety. J Complementary Integr Med 2010;7:18-22.  Back to cited text no. 23
Green S. Benzodiazepines, putative anxiolytics and animal models of anxiety. Trends Neurosci 1991;14:101-4.  Back to cited text no. 24
Komaki A, Abdollahzadeh F, Sarihi A, Shahidi S, Salehi I. Interaction between antagonist of cannabinoid receptor and antagonist of adrenergic receptor on anxiety in male rat. Basic Clin Neurosci. 2014;5:218-24.  Back to cited text no. 25
Wilson MA, Burghardt PR, Ford KA, Wilkinson MB, Primeaux SD. Anxiolytic effects of diazepam and ethanol in two behavioral models: Comparison of males and females. Pharmacol Biochem Behav 2004;78:445-58.  Back to cited text no. 26
Silva LF, Lima ES, Vasconcellos MC, Aranha ES, Costa DS, Mustafa EV, et al.In vitro and in vivo antimalarial activity and cytotoxicity of extracts, fractions and a substance isolated from the Amazonian plant Tachia grandiflora (Gentianaceae). Mem Inst Oswaldo Cruz 2013;108:501-7.  Back to cited text no. 27
Asami DK, Hong YJ, Barrett DM, Mitchell AE. Comparison of the total phenolic and ascorbic acid content of freeze-dried and air-dried marionberry, strawberry, and corn grown using conventional, organic, and sustainable agricultural practices. J Agric Food Chem 2003;51:1237-41.  Back to cited text no. 28
Rex A, Morgenstern E, Fink H. Anxiolytic-like effects of Kava-Kava in the elevated plus maze test – A comparison with diazepam. Prog Neuropsychopharmacol Biol Pschiatry 2002;26:855-8.  Back to cited text no. 29
Souto-Maior FN, de Carvalho FL, de Morais LC, Netto SM, de Sousa DP, de Almeida RN. Anxiolytic-like effects of inhaled linalool oxide in experimental mouse anxiety models. Pharma Bio Behav 2011;100:259-63.  Back to cited text no. 30
Gomes PB, Feitosa ML, Silva MI, Noronha EC, Moura BA, Venâncio ET, et al. Anxiolytic-like effect of the monoterpene 1,4-cineole in mice. Pharmaco Bioche Behav 2010;96:287-93.  Back to cited text no. 31
Takahashi RN, Berton O, Mormède P, Chaouloff F. Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze. Braz J Med Biol Res 2001;34:675-82.  Back to cited text no. 32
Ding L, Zhang C, Masood A, Li J, Sun J, Nadeem A, et al. Protective effects of phosphodiesterase 2 inhibitor on depression- and anxiety-like behaviors: Involvement of antioxidant and anti-apoptotic mechanisms. Behav Brain Res 2014;268:150-8.  Back to cited text no. 33
de Almeida AA, de Carvalho RB, Silva OA, de Sousa DP, de Freitas RM. Potential antioxidant and anxiolytic effects of (+)-limonene epoxide in mice after marble-burying test. Pharmacol Biochem Behav 2014;118:69-78.  Back to cited text no. 34
Oliveira MR, Silvestrin RB, Mello E, Souza T, Moreira JC. Oxidative stress in the hippocampus, anxiety-like behavior and decreased locomotory and exploratory activity of adult rats: Effects of sub acute vitamin A supplementation at therapeutic doses. Neurotoxicology 2007;28:1191-9.  Back to cited text no. 35
Masood A, Nadeem A, Mustafa SJ, O'Donnell JM. Reversal of oxidative stress-induced anxiety by inhibition of phosphodiesterase-2 in mice. J Pharmacol Exp Ther 2008;326:369-79.  Back to cited text no. 36
Vollert C, Zagaar M, Hovatta I, Taneja M, Vu A, Dao A, et al. Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: Potential role of oxidative stress mechanisms. Behav Brain Res 2011;224:233-40.  Back to cited text no. 37
Salim S, Sarraj N, Taneja M, Saha K, Tejada-Simon MV, Chugh C. Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats. Behav Brain Res 2010;208:545-52.  Back to cited text no. 38
Salim S, Asghar M, Chugh G, Taneja M, Xia Z, Saha K. Oxidative stress: A potential recipe for anxiety, hypertension and insulin resistance. Brain Res 2010;1359:178-85.  Back to cited text no. 39
Souza CG, Moreira JD, Siqueira IR, Pereira AG, Rieger DK, Souza DO, et al. Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior. Life Sci 2007;81:198-203.  Back to cited text no. 40
Bouayed J, Rammal H, Younos C, Soulimani R. Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice. Eur J Pharmacol 2007;564:146-9.  Back to cited text no. 41
Nahrstedt A, Schmidt M, Jäggi R, Metz J, Khayyal MT. Willow bark extract: The contribution of polyphenols to the overall effect. Wien Med Wochenschr 2007;157:348-51.  Back to cited text no. 42