Anti-Anxiety Effects of Artemisia persica in Male Rats

Document Type: Original paper


1 Medical Plants Research Center, Basic Health Sciences Institue, Shahrekord University of Medical Sciences, Shahrekord, Iran.

2 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran


Background and objective: Anxiety is one of the most common diseases in human societies. Since Artemisia persica has a significant antioxidant capacity with phenolic compounds, and thesesubstances have anti-anxiety effect, the purpose of this research was to determine theAnti-anxiety like effects of Iranian Artemisia persica extract in male rats. Methods: Artemisia persica hydroalcoholic extract was prepared by maceration method.  Animals were divided into 5 experimental groups. The first group was injected with normal saline. Groups 2 to 4 were injected with Artemisia persica extract at doses of 100, 200 and 400 mg/kg. The fifth group received 2.1 mg/kg of diazepam. The ability to maintain balance of the rates was measured using the rotarod device, anxiety was measured with elevated plus maze, and the motor activity was measured by the open field device. Antioxidant capacity and malondialdehyde levels were also measured in brain and serum tissues. Results: Intraperitoneal injection of doses of 100 and 200 mg/kg of the extract increased the number of entering and presence time in the open arm of the plus maze. Doses of 100 and 200 mg/kg of the extract showed significant increase in antioxidant capacity and significant reduction in malondialdehyde levels. In these experiments, the dose of 400 mg/kg showed less effect and in somecases reversed the effects. Conclusion: it seems that the anti-anxiety effect of Artemisia persica is dose dependent and increases by increasing the dose to 200 mg/kg; however, at higher dose (400 mg/kg) it shows pro-oxidant effects.


Main Subjects

[1] Mora S, Millán R, Lungenstrass H, Díaz-Véliz G, Morán J, Herrera-Ruiz M, Tortoriello J. The hydroalcoholic extract of Salvia elegans induces anxiolytic-and antidepressant-like effects in rats. J Ethnopharmacol. 2006; 106(1): 76-81.
[2] Kumar D, Bhat ZA. Apigenin 7-glucoside from Stachys tibetica Vatke and its anxiolytic effect in rats. Phytomed. 2014; 21(7): 1010-1014.
[3] Kandel ER, Schwartz JH, Jessell TM, Biochemistry Do, Jessell MBT, Siegelbaum S, Hudspeth AJ. Principles of neural science. New York: McGraw-hill, 2000.
[4] Elayaraja A, Rahaman SA, Kumar P. Anti-anxiety activity of hydro alcoholic extract of Scoparia dulcis Linn. assessed using different experimental anxiety models In rodents. Int J Pharmacol Res. 2015; 5(3): 62-67.
[5] Rafsanjani FN, Shahrani M, Ardakani ZV, Ardakani MV. Marjoram increases basal gastric acid and pepsin secretions in rat. Phytother Res. 2007; 21(11): 1036-1038.
[6] Singh N, Kaur S, Bedi P, Kaur D. Anxiolytic effects of Equisetum arvense Linn. extracts in mice. Indian J Exp Biol. 2011; 49(5): 352-356.
[7] Zaidi SKR, Al-Qirim TM, Banu N. Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation induced by restraint stress in the rat liver. Drugs in R & D. 2005; 6(3): 157-165.
[8] Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci. 2005; 8(3): 394-399.
[9] Rector NA, Laposa JM, Kitchen K, Bourdeau D, Joseph-Massiah L. Anxiety disorders: an information guide. Toronto: Centre for Addiction and Mental Health, 2016.
[10] Ayankunle A, Wakeel O, Kolawole O, Oyekale A, Ojurongbe O, Adeyeba O. Drug repositioning: antimalarial activities of GABA analogs in mice infected with Plasmodium berghei. Cent Nerv Syst Agents Med Chem. 2020; Article ID 32496991.
[11] Gilani AH, Yaeesh S, Jamal Q, Ghayur MN. Hepatoprotective activity of aqueous-methanol extract of Artemisia vulgaris. Phytother Res. 2005; 19(2): 170-172.
[12] Le Tran Q, Tezuka Y, Ueda JY, Nguyen NT, Maruyama Y, Begum K, Kim HS, Wataya Y, Tran QK, Kadota S. In vitro antiplasmodial activity of antimalarial medicinal plants used in Vietnamese traditional medicine. J Ethnopharmacol. 2003; 86(2-3): 2249-2252.
[13] Tigno XT, De Guzman F, Flora AM, Theresa V. Phytochemical analysis and hemodynamic actions of Artemisia vulgaris L. Clin Hemorheol Microcirc. 2000; 23(2): 167-175.
[14] Chen V, Ianuzzo CD. Dosage effect of streptozotocin on rat tissue enzyme activities and glycogen concentration. Can J Physiol Pharm. 1982; 60(10): 1251-1256.
[15] Rodrigues-Alves R, Pregal A, Pereira-Santos M, Branco-Ferreira M, Lundberg M, Öman H, Pereira M. Anaphylaxis to pine nut: cross-reactivity to Artemisia vulgaris? Allergol Immunopathol. 2008; 36(2): 113-116.
[16] Mohammadpoor SK, Yari M, Rustaiyan A, Masoudi S. Chemical constituents of the essential oil of Artemisia aucheri Boiss. a species endemic to Iran. J Essent Oil Res. 2002; 14(2): 122-123.
[17] Naghibi F, Mosadegh M, Mohammadi MS, Ghorbani A. Labiatae family in folk medicine in Iran: from ethnobotany to pharmacology.  Iran J Pharm Res. 2010; 4(2): 63-79.
[18] Nikbakht MR, Sharifi S, Emami SA, Khodaie L. Chemical composition and antiprolifrative activity of Artemisia persica Boiss. and Artemisia turcomanica Gand. essential oils. Res Pharm Sci. 2014; 9(2): 155-163.
[19] Kim SS, Lee CK, Kang SS, Jung HA, Choi JS. Chlorogenic acid, an antioxidant principle from the aerial parts of Artemisia iwayomogi that acts on 1, 1-diphenyl-2-picrylhydrazyl radical. Arch Pharm Res. 1997; 20(2):148-150.
[20] Mahmoudi M, Ebrahimzadeh M, Ansaroudi F, Nabavi S, Nabavi S. Antidepressant and antioxidant activities of Artemisia absinthium L. at flowering stage. Afr J Biotechnol. 2009; 8(24): 7170-7175.
[21] Eidi A, Oryan S, Zaringhalam J, Rad M. Antinociceptive and anti-inflammatory effects of the aerial parts of Artemisia dracunculus in mice. Pharm Biol. 2016; 54(3): 549-554.
[22] Shishehgar R, Rezaie A, Nazeri M. Study of sedation, pre-anesthetic and anti-anxiety effects of hop (Humulus lupulus L.) extract compared with diazepam in rats. J Anim Vet Adv. 2012. 4(2): 120-124.
[23] Wongwitdecha N, Marsden C. Social isolation increases aggressive behavior and alters the effects of diazepam in the rat social interaction test. Behav Brain Res.1996; 75(1-2): 27-32.
[24] Altarifi A, Alsalem M, Mustafa A. Effects of intraplantar administration of Complete Freund's Adjuvant (CFA) on rotarod performance in mice. 2019; Scand J Pain. 19(4): 805-811.
[25] Rodgers R, Dalvi A. Anxiety, defence and the elevated plus-maze. Neurosci Biobehav Rev. 1997; 21(6): 801-810.
[26] Gould TD, Dao DT, Kovacsics CE. The open field test.  Mood and anxiety related phenotypes in mice. New York: Humana Press; 2009.
[27] 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; (3): 149-167.
[28] Benzie IF, Strain J. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration.  Methods Enzymol. 1999; 299(3): 15-27.
[29] Fathi F, Oryan S, Rafieian-KopaeI M, Eidi A. Neuroprotective effect of pretreatment with Mentha longifolia L. extract on brain ischemia in the rat stroke model. Arc Biol Sci. 2015; 67(4): 1151-1163.
[30] Raghav S, Gupta B, Agrawal C, Goswami K, Das H. Anti-inflammatory effect of Ruta graveolens L. in murine macrophage cells. J Ethnopharmacol. 2006; 104(1-2): 234-239.
[31] Rashidch A, Qureshi MZ, Raza SA, William J, Arshad M. Quantitative determination of antioxidant potential of Artemisia persica. An Univ Bucuresti Chimie. 2010; 19(1): 23-30.
[32] Korrani MS, Farbood Y, Sarkaki A, Moghaddam HF, Mansouri MT. Protective effects of gallic acid against chronic cerebral hypoperfusion-induced cognitive deficit and brain oxidative damage in rats. Eur J Pharmacol. 2014; 733(2): 62-67.
[33] Bouayed J, Rammal H, Dicko A, Younos C, Soulimani R. Chlorogenic acid, a polyphenol from Prunus domestica (Mirabelle), with coupled anxiolytic and antioxidant effects. J Neuro Sci. 2007; 262(1-2): 77-84.
[34] Mirzaei A, Akbartabar M, Sadeghi H, Sharifi B. The antioxidant activities and total phenolic of Artemisia martima, Achillea millefolium and Matricaria recutica. Armaghane Danesh. 2010; 15(3): 243-252.
[35] Tallman JF, Paul SM, Skolnick P, Gallager DW. Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science. 1980; 207(4428): 274-281.
[36] Awad R, Levac D, Cybulska P, Merali Z, Trudeau V, Arnason J. Effects of traditionally used anxiolytic botanicals on enzymes of the γ-aminobutyric acid (GABA) system. Can J Physiol Pharmacol. 2007; 85(9): 933-942.
[37] Söderpalm B, Eriksson E, Engel JA. Anti-conflict and rotarod impairing effects of alprazolam and diazepam in rat after acute and subchronic administration. Prog Neuropsychopharmacol Biol Psychiatry. 1989; 13(1-2): 269-283.
[38] Musavi S, Kakkar P. Effect of diazepam treatment and its withdrawal on pro/antioxidative processes in rat brain. Mol Cell Biochem. 2003; 245(1-2): 51-56.
[39] Shen XL, Nielsen M, Witt MR, Sterner O, Bergendorff O, Khayyal M. Inhibition of [methyl-3H] diazepam binding to rat brain membranes in vitro by dinatin and skrofulein. Acta pharmacologica Sinica. 1994; 15(5): 385-388.
[40] Emadi F, Yassa N, Hadjiakhoondi A, Beyer C, Sharifzadeh M. Sedative effects of Iranian Artemisia annua in mice: possible benzodiazepine receptors involvement. Pharm Biol. 2011; 49(8): 784-788.
[41] Sharma A, Cardoso-Taketa A, García G, Villarreal ML. A systematic updated review of scientifically tested selected plants used for anxiety disorders. Botanics. 2012; 14(2): 21-39.