Anti-anxiety and hypnotic effects of ethanolic and aqueous extracts of Lippia citriodora leaves and verbascoside in mice

Document Type : Original Research Article

Authors

1 Targeted Drug Delivery Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences

2 School of Pharmacy, Mashhad University of Medical Sciences

3 Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objectives: The extract of Lippia citriodora and its main component, verbascoside, are known for their hypnotic effects in traditional medicine. In this study, the anxiolytic and hypnotic effects of L. citriodora leave extracts and verbascoside were evaluated in mice.
Materials and Methods: Animals were divided into 11 groups of six mice each. Group I received normal saline, Group II received Diazepam (2 mg/kg) as positive control, Groups III, IV and V received L. citriodora ethanolic extracts (50, 100 and 200 mg/kg, respectively), Groups VI, VII and VIII received L. citriodora aqueous extracts (50, 100 and 200 mg/kg, respectively) and Groups IX, X and XI received Verbascoside (25, 50 and 100 mg/kg, respectively). All agents were administrated intraperitoneally. To evaluate hypnotic activity, pentobarbital sleeping test, and for anxiolytic activity, elevated plus-maze (EPM), locomotor activity, open field and motor coordination (rotarod test) tests were used. To understand the role of GABAA receptor, flumazenil was also administered.
Results: The extracts and verbascoside increased the time spent and number of entries in the open arms of EPM. Moreover, these agents significantly increased the sleeping time induced by pentobarbital. In addition, the highest dose of extracts and verbascoside reduced time spent on the rod and total locomotion in the open field tests, respectively. Flumazenil inhibited the effects of extracts and verbascoside in EPM and hypnotic tests.
Conclusion: These results suggested that ethanolic and aqueous extracts of L. citriodora and verbascoside exhibit anxiolytic, hypnotic and muscle relaxant effects especially at the highest doses and these effects are partially due to the interaction with GABAA receptor.

Keywords

Main Subjects

References

Alavi L, Barzegar M, Jabbari A, Naghdi badi H.2011. The Effect of Heat Treatment on Chemical Composition and Antioxidant Property of Lippia citriodora Essential Oil.J Med Plants, 3: 65-75.
Amin B, Poureshagh E, Hosseinzadeh H. 2016. The Effect of Verbascoside in Neuropathic Pain Induced by Chronic Constriction Injury in Rats. Phytother Res,  30: 128-135.
Bouayed J, Rammal H, Soulimani R.2009. Oxidative stress and anxiety. Relationship and cellular pathways.Oxid Med Cell Longev,  2: 63-67.
Bozorgmehr B, Mojab F, Faizi M. 2012. Evaluation of sedative-hypnotic effect of ethanolic extract of five medicinal plants; Nepeta menthoides, Matricaria chamomilla, Asperugo procumbens, Lippia citriodora and Withania somnifera. Res Pharm Sci, 7(5).
Campo G, Pavasini R, Biscaglia S, Ferri A, Andrenacci E, Tebaldi M.2015. Platelet aggregation values in patients with cardiovascular risk factors are reduced by verbascoside treatment. A randomized study. Pharmacol Res, 97: 1-6.
Di Giancamillo A, Rossi R, Pastorelli G, Deponti D, Carollo V, Casamassima D. 2015. The effects of dietary verbascoside on blood and liver oxidative stress status induced by a high-6 polyunsaturated fatty acids diet in piglets. J Animal Sci, 93: 2849-2859.
Eidi M, Ilchizadeh Kavgani A, Shahabzadeh S, Sasaninezhad Z, Ghahramani R, Hamidi Nomani M.2014. Effect of Lippia Citriodora on Anxiety Behaviour in Adult Male Rat. Med J Tabriz Univ Med Sci, 36: 68-73.
El-Hawary S S, Yousif M F, Abdel Motaal A AAbd-Hameed L M.2012. Bioactivities, phenolic compounds and in-vitro propagation of Lippia citriodora Kunth cultivated in Egypt.Bull Fac Pharm (Cairo Univ), 50: 1-6.
Ernst E.2006. Herbal remedies for anxiety – a systematic review of controlled clinical trials. Phytomedicine, 13: 205–208.
Esposito E, Dal Toso R, Pressi G, Bramanti P, Meli R, Cuzzocrea S.2010. Protective effect of verbascoside in activated C6 glioma cells: possible molecular mechanisms.Naunyn Schmiedebergs Arch Pharmacol, 381: 93-105.
Fachinetto R, Villarinho J, Wagner C, Pereira R, Avila D, Burger M, Calixto J, Rocha J, Ferreira J. 2007. Valeriana officinalis does not alter the orofacial dyskinesia induced by haloperidol in rats: Role of dopamine transporter. Prog Neuropsychopharmacol Biol Psychiatry, 31: 1478-1486.
Feliu-hemmelmann K, Monsalve F, Rivera C.2013. Melissa officinalis and Passiflora caerulea infusion as physiological stress decreaser. Int  J Clin Exp Med, 6: 444.
Gao L, Peng X-M, Huo S-X, Liu X-MYan M.2015. Memory Enhancement of Acteoside (Verbascoside) in a Senescent Mice Model Induced by a Combination of d-gal and AlCl3.Phytother Res, 29: 1131-1136.
Greenblattab D, Shader R.1978 Dependence, Tolerance, and Addiction to Benzodiazepines: Clinical and Pharmacokinetic Considerations. Drug Met  Rev, 8: 13-28.
Hosseinzadeh H, Sadeghnia H.2007. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems. Phytomedicine, 14: 256-262.
Hossinzadeh H, Norani N B.2009. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother  Res, 23: 768-774.
Hosseinzadeh H, Shahandeh S, Shahsavand S. 2012. Anxiolytic and hypnotic effects of aqueous and ethanolic extracts of aerial parts of Echium italicum L. in mice. Jundishapur J Nat Pharm Prod, 7: 71-79. 
Hosseinzadeh H, Danaee A, Ziaee T. 2008. Anti-anxiety effect of aqueous and ethanolic extracts of Salvia leriifolia Benth. leaves in mice using elevated plus maze. J Med Plants, 7: 25-36.
Hui K, Huen M, Wang H, Zheng H, Sigel E, Baur R.2002. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochem Pharmacol, 64: 1415-1424.
Isacchi B, Iacopi R, Bergonzi M, Ghelardini C, Galeotti N, Norcini Mal. 2011. Antihyperalgesic activity of verbascoside in two models of neuropathic pain. J Pharm Pharmacol, 63: 594-601.
Koo K, Kim S, Oh T, Kim Y.2006. Acteoside and its aglycones protect primary cultures of rat cortical cells from glutamate-induced excitotoxicity. Life Sci, 79: 709-716.
Koohsari H, Ghaemi E, Sadegh Shesh P, oli M, Sadegh A.2013. Evaluation of antibacterial activity of Lemon verbena (Lippiacitriodora) leaves. Ann Biol Res, 4:52-55.
Kuroda M, Iwabuchi K, Mimaki Y.2012. Chemical constituents of the aerial parts of Scutellaria lateriflora and their alpha-glucosidase inhibitory activities. J Nat Prod, 7: 471-474.
Lenoir L, Rossary A, Joubert-Zakeyh J, Vergnaud-Gauduchon J, Farges M-C, Fraisse D, Texier O, Lamaison Lenoir L, Vasson M-PFelgines C.2011. Lemon Verbena Infusion Consumption Attenuates Oxidative Stress in Dextran Sulfate Sodium-Induced Colitis in the Rat. Digest Dis Sci, 56: 3534-3545.
Liang J-q, Wang L, He J-c, Hua X-d.2016. Verbascoside promotes the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Neural Regen Res, 11: 101.
Liberzon I, Phan K, Khan S, Abelson J.2003. Role of the GABAA receptor in anxiety: evidence from animal models, molecular and clinical psychopharmacology, and brain imaging studies. Curr Neuropharm, 1: 267-283.
Mehrabizadeh Honarmand M, Arzi A, Aghal N, Goodarzi S.2011.Anti-nociceptive effect of hydroalcoholic extract of Lippia citriodora kunth in rat using formalin test. Tox lett, 205:S90.
Moura F, de Andrade K, dos Santos J, Araújo OGoulart M. 2015. Antioxidant therapy for treatment of inflammatory bowel disease: Does it work? Redox biol, 6: 617-639.
Nikolaus S, Antke C, Beu M, Muller H-W.2010. Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders-results from in vivo imaging studies. Rev Neurosci, 21: 119-140.
Oskouei Shirvan Z, Etemad L, Zafari R, Moallem SA, Vahdati-Mashhadian N, Hosseinzadeh H.2016. Teratogenic effect of Lippia citriodora leaves aqueous extract inmice. Avicenna J Phytomed, 6:175-80.
Pardon M, Perez Diaz F, Joubert C, Cohen Salmon C.2000. Age dependent effects of a chronic ultramild stress procedure on open field behavior in B6D2F1 female mice. Physiol Behav, 70: 7-13.
Pascual M E, Slowing K, Carretero E, Sánchez Mata D, Villar A.2001. Lippia: traditional uses, chemistry and pharmacology: a review.J Ethnopharmacol, 76: 201-214.
Pastorelli G, Rossi R, Corino C.2012. Influence of Lippia citriodora verbascoside on growth performance, antioxidant status, and serum immunoglobulins content in piglets. Czech J Animal Sci, 57: 312-322.
Pereira A, Hernandes C, Pereira S, Bertoni B, França S, Pereira P.2014. Evaluation of anticandidal and antioxidant activities of phenolic compounds from Pyrostegia venusta (Ker Gawl.) Miers. Chemico-biol inter, 224:136-41.
Portmann E, Nigro MM, Reides CG, Llesuy S, Ricco RA, Wagner ML, Gurni AA, Carballo MA. 2012.
Aqueous extracts of Lippia turbinata and Aloysia citriodora (Verbenaceae): assessment of antioxidant capacity and DNA damage. Int J Toxicol, 31:192-202.
Sanchez P, Villarreal M, Herrera-Ruiz M, Zamilpa  A, Jiménez-Ferrer  E, Trejo-Tapia G. 2013. In vivo anti-inflammatory and anti-ulcerogenic activities of extracts from wild growing and in vitro plants of Castilleja tenuiflora Benth. (Orobanchaceae). J ethnopharmacol, 150:1032-1037.
Shin I C, Kim H C, Swanson J, Hong J, TOh,  KW. 2003. Anxiolytic effects of acute morphine can be modulated by nitric oxide systems. Pharmacology, 68: 183-189.
Skaltsa H, Shammas G.1988. Flavonoids from Lippia citriodora. Planta Med, 54: 465.
Walf A A, Frye C A.2007. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protocols, 2: 322-328.
Veisi M, Shahidi S, Komaki A, Sarihi A.2016. Assessment of aqueous extract of Lemon verbena on anxiety‑like behavior in rats. J Pharm Negat Results, 6:37-39.
Wolfman C, Viola H, Marder M, Wasowski C, Ardenghi P, Izquierdo I.1996. Anxioselective properties of 6,3’-dinitroflavone, a high-affinity benzodiazepine receptor ligand. Eur J Pharmacol, 318: 23-30.
Yousef zadeh N, Meshkatalsadat MH.2013. Quantitative and qualitative study of bioactive compounds of essential oils of plant Lippia citriodora by use of gc-ms technique. J Novel Appl Sci, 2: 964-968.
Ziaee T, Hosseinzadeh, H. 2010. Muscle relaxant, hypnotic and anti-anxiety effects of Pistacia vera gum hydroalcoholic extract in mice. J Med Plants, 9: 96-105.
Zhang Y, Liu B, Wu H, Li B, Xu J, Duan L.2014. Anti-Tumor Activity of Verbascoside Loaded Gold Nanoparticles. J biom Nanotechnol, 10: 3638-3646.
Zhu M, Zhu H, Tan N, Wang H, Chu H, Zhang C. 2016. Central anti-fatigue activity of verbascoside. Neurosci Let. 616:75-79.
Wu YT, Lin LC, Tsai TH. 2009. Measurement of free hydroxytyrosol in microdialysates from blood and brain of anesthetized rats by liquid chromatography with fluorescence detection. J Chromatogr  A. 1216: 3501-3507.
 
Avicenna Journal of Phytomedicine
Volume 7, Issue 4
July and August 2017
Pages 353-365

Files

Share

How to cite

Statistics