Effect of Withania somnifera Dunal Root Extract on Behavioral Despair Model in Mice: a Possible Role for Nitric Oxide
Abstract
Withania somnifera (WS) possess anti-inflammatory and antioxidant properties. WS preparations have a potential therapeutic role in the central nervous system (CNS) related disorders in animal models. In this study, the possible protective effect of acute aqueous WS root extract on behavioral despair was explored and compared with fluoxetine, an antidepressant with selective serotonin (5-HT) reuptake inhibitor activity (SSRI). Further, the probable involvement of nitric oxide (NO) determined to measure immobility time in forced swimming test (FST) and tail suspension test (TST) in male mice. Immediately after assessment of locomotor activity, the immobility time was evaluated. WS was administered intraperitoneally (200, 400 mg/kg; i.p.) 60 min before the behavioral tests. To assess the involvement of NO in the possible protective effect of WS, a non-specific NO synthase inhibitor, NG-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.) was administered 30 min before the extract administration (400 mg/kg, i.p.), 90 min before the tests. Acute WS extract (200, 400 mg/kg, i.p.) dose-dependently decreased the immobility time in FST, P<0.05, P<0.001, respectively and 400 mg/kg proved the most effective dose and this dose was comparable to fluoxetine (20 mg/kg, i.p. WS (400 mg/kg, i.p.) also lowered the immobility measure in TST (P<0.05). However, these effects were not related to change in locomotor activity. Moreover, L-NAME (10 mg/kg, i.p.) did not influence the effect of the extract on the behavioral tests. As a consequence, the immobility time was virtually constant between the group received the extract (400 mg/kg) alone, and the group received L-NAME (10 mg/kg) before the extract. It is probable that NO does not mediate this beneficial effect, and WS may affect other neurochemical systems and pathways.
Chopra K, Kumar B, Kuhad A. Pathobiological targets of depression. Expert Opin Ther Targets2011;15(4):379-400.
Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997;349(9064):1498-504.
Hindmarch I, Hashimoto K. Cognition and depression: The effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered. Hum. Psychopharmacol 2010;25(3):193-200.
van Amsterdam JG, Opperhuizen A. Nitric oxide and biopterin in depression and stress. Psychiatry Res1999;85(1):33-8.
De Vente J, Hopkins DA, Markerink-Van Ittersum M, et al. Distribution of nitric oxide synthase and nitric oxidereceptive, cyclic GMP-producing structures in the rat brain. Neuroscience 1998;87(1):207-41.
Dhir A, Kulkarni SK. Involvement of nitric oxide (NO) signaling pathway in the antidepressant action of bupropion, a dopamine reuptake inhibitor. Eur J Pharmacol 2007;568(1-3):177-85.
Joca SR, Guimaraes FS. Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressantlikeeffects. Psychopharmacology 2006;185(3):298-305.
Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression.Trends Immunol 2006;27(1):24-31.
Dantzer R, O'Connor JC, Freund GG, et al. Frominflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9(1):46-56.
Peng YL, Liu YN, Liu L, Wang X, Jiang CL, Wang YX. Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced byunpredictable chronic mild stress. J Neuroinflammation. 2012;(6): 9:75.
Sarris J. Herbal medicines in the treatment of psychiatric disorders: Systematic review. Phytother Res 2007;21(8):703-16.
Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev 2008 ;(4):CD000448.
Akhondzadeh Basti A, Moshiri E, Noorbala AA, et al. Comparison of petal of Crocus sativus L and fluoxetine in the treatment of depressed outpatients: A pilot doubleblind, randomized trial. Prog. Neuro-Psychopharmacol. Prog Neuropsychopharmacol Biol Psychiatry 2007;31(2):439-42.
Akhondzadeh S, Kashani L, Fotouhi A, Jarvandi S, Mobaseri M, Moin M, Khani M, Jamshidi AH, Baghalian K, Taghizadeh M. Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild tomoderate depression: a double-blind, randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(1):123-7.
Andallu B, Radhika B. Hypoglycemic diuretic and hypocholesterolemic effect of winter cherry (Withaniasomnifera Dunal) root. Indian J Exp Biol 2000;38(6):607-9.
Uddin Q, Samiulla L., Singh VK, et al. Phytochemical and Pharmacological Profile of Withania somnifera Dunal: AReview. J Appl Pharmaceutical Sci 2012;2(1);170-5.
Dafni A, Yaniv Z. Solanaceae as medicinal plants in Israel. J Ethnopharmacol 1994;44(1):8-11.
Bhatia P, Rattan SIS, Cavallius J, et al. Withania somnifera (Ashwagandha) a so-called rejuvenator inhibits growth andmacromolecular synthesis of human cells. Med Sci Res1987;15:515-6.
Singh B, Saxena AK, Chandan BK, et al. Adaptogenic activity of a novel withanolide-free aqueous fraction fromthe roots of Withania somnifera Dun. Phytother Res 2001;15(4):311-8.
Sahni YP & Srivastava DN. Inhibition of gastric ulcer by Indigenous medicines Withania sominifera, Indian Vet Med J, 1994;18: 42-43.
Bhattacharya SK. Evaluation of adaptogenic activity of some Indian medicinal plants. Withania somnifera and Ocimum sanctum with special reference to stress-induced gastric ulcer in albino rats. Proc Intl Seminar on Traditional Med Calcutta 1992 ;( 1):7-9.
Rege NN, Thatte UM, Dahanukar SA. Adaptogenic activity of six rasayana herbs used in Ayurvedic medicine.Phytotherapy Res 1999;13(4):275-91.
Kulkarni SK, George B. Anticonvulsant action of Withania somnifera (Ashwagandha) root extract againstpentylenetetrazol-induced kindling in mice. Phytother Res 1996;10(5):447-9.
Dhuley JN. Effect of ashwagandha on lipid peroxidation instress-induced animals. J Ethnopharmacol 1998;60(2):173-8.
Panda S, Kar A. Evidence for free radical scavengingactivity of Ashwagandha root powder in mice. Indian JPhysiol Pharmacol 1997;41(4):424-6.
Parihar MS, Hemnani T. Phenolic antioxidants attenuatehippocampal neuronal cell damage against kainic acidinduced excitotoxicity. J Biosci 2003;28(1):121-8.
Russo A, Izzo AA, Cardile V, et al. Indian medicinalplants as antiradicals and DNA cleavage protectors. Phytomedicine 2001;8(2):125-32.
Bhattacharya SK, Satyan KS, Chakrabarti A. Effect ofTransina (TR), an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase (SOD) activity inhyperglycaemic rats. Indian J Exp Biol 1997;35(3):297-9.
Khare CP. Indian Medicinal Plants–An Illustrated Dictionary. 1st ed. New York: Springer;2007: p. 717-8.
Elsakka M, Grigorescu E, Stanescu U, et al. New data referring to chemistry of Withania somnifera species. Rev Med Chir Soc Med Nat Iasi 1990;94(2):385-7.
Grandhi A, Mujumdar AM, Patwardhan B. A comparativepharmacological investigation of Ashwagandha andGinseng. J Ethnopharmacol 1994;44(3):131-5.
Thakur RS, Puri HS, Hussain A. Major medicinal plants of India. 1st ed. Lucknow, India: Central Institute ofMedicinal and Aromatic Plants;1989.
Puri HS, editor. Simple Ayurvedic Remedies. 1st ed. New Delhi: UBS Publisher Distributors;2002.
Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha) a review. Altern Med Rev 2000;5(4):334-46.
Matsuda H, Murakami T, Kishi A, Yoshikawa M. Structures of withanosides I II III IV V VI and VII newwithanolide glycosides from the roots of Indian Withaniasomnifera DUNAL and inhibitory activity for tachyphylaxis to clonidine in isolated guinea-pig ileum. Bioorg Med Chem 2001;9(6):1499-507.
Choudhary MI, Nawaz SA, ul-Haq Z, et al. Withanolides anew class of natural cholinesterase inhibitors withcalciumantagonistic properties. Biochem Biophys ResCommun 2005;334(1):276-87.
Rao PR, Rao KT, Srivastava RS, et al. Effect ofglycowithanolides from Withania somnifera on morphineinducedinhibition of intestinal motility and tolerance of analgesia in mice. Phytother Res 1995;9(1):66-8.
Kulkarni SK, Ninan I. Inhibition of morphine toleranceand dependence by Withania somnifera in mice. JEthnopharmacol. 1997;57(3):213-7.
Malhotra CL, Mehta VL, Das PK, et al. Studies on Withania ashwagandha Kaul V the effect of total alkaloids (ashwagandholine) on the central nervous system. Indian J Physiol Pharmacol 1965;9(3):127-36.
Bhattacharya A, S.K., Kumar A., Schliebs R, Liebmann A, Bhattacharya SK, et al. Systemic administration of defined extracts from Withania somnifera (Indian ginseng)and Shilajit differentially affect cholinergic but notglutamergic and GABAergic markers in rat brain. Neurochem Int 1997;30(2):181-90.
Devi PU, Sharada AC, Solomon FE, et al. In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a transplantable mouse tumor Sarcoma 180. Indian J Exp Biol 1992;30(3):169-72.
Mohan R, Hammers HJ, Bargagna-Mohan P, et al. Withaferin A is a potent inhibitor of angiogenesis. Angiogenesis 2004;7(2):115-22.
Rai D, Bhatia G, Sen T, Palit G. Anti-stress effects of Ginkgo biloba and Panax ginseng a comparative study. J Pharmacol Sci 2003;93(4):458-64.
Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol 1999;64(1):91-3.
Bhattacharya SK, Muruganandam AV. Adaptogenicactivity of Withania somnifera an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav 2003;75(3):547-55.
Ahmad M, Saleem S, Ahmad AS, et al. Neuroprotectiveeffects of Withania somnifera on 6-hydroxydopamineinduced Parkinsonism in rats. Hum Exp Toxicol 2005;24(3):137-47.
Chaudhary G, Sharma U, Jagannathan NR, et al. Evaluation of Withania somnifera in a middle cerebralartery occlusion model of stroke in rats. Clin Exp Pharmacol Physiol 2003;30(5-6):399-404.
Panda S, Kar A. Changes in thyroid hormoneconcentrations after administration of Ashwagandha root extract to adult male mice. J Pharm Pharmacol1998;50(9):1065-8.
Mohanty I, Arya DS, Dinda A, et al. Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction. Basic Clin Pharmacol Toxicol 2004;94(4):184-90.
Owolabi RA, Akanmu MA, Adeyemi OI. Effects of ketamine and N-methyl-D-aspartate on fluoxetine-induced antidepressant-related behavior using the forced swimming test. Neurosci Lett 2014;566:172-6.
Sadaghiani MS, Javadi-Paydar M, Gharedaghi MH, et al. Antidepressant-like effect of pioglitazone in the forced swimming test in mice: The role of PPAR-gamma receptor and nitric oxide pathway. Behav Brain Res 2011;224(2):336-43.
Ghasemi M, Raza M, Dehpour AR. NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test. J Psychopharmacol 2010;24(4):585-94.
Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229(2):327-36.
Refaey El H, Amri HS, SSC-Psych. Effects of antidepressants on behavioral assessment in adolescent rats. Bahrain Med Bull 2011;33(2):83-95.
Dhingra D, Sharma A. Evaluation of antidepressant-like activity of glycyrrhizin in mice. Indian J Pharmacol 2005;37(6):390-4.
Steru L, Chermat R, Thierry B, et al. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985;85(3):367-70.
Mantovani M, Pértile R, Calixto JB, et al. Melatonin exerts an antidepressant-like effect in the tail suspension test in mice: Evidence for involvement of N-methyl-D-aspartate receptors and the L-arginine-nitric oxide pathway. Neurosci Lett 2003;343(1):1-4.
Mehta AK, Binkley P, Gandhi SS, et al. Pharmacological effects of Withania somnifera root extract on GABAA receptor complex. Indian J Med Res 1991;94:312-5.
Schliebs R, Liebmann A, Bhattacharya SK, et al. Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain. Neurochem Int 1997;30(2):181-90.
Tohda C, Kuboyama T, Komatsu K. Search for natural products related to regeneration of the neuronal network. Neurosignals 2005;14(1-2):34-45.
Jain S, Shukla SD, Sharma K, et al. Neuroprotective effects of Withania somnifera Dunn in hippocampal subregions of female albino rat. Phytother Res 2001;15(6):544-88.
Bhattacharya A, Muruganandam AV, Kumar V, Bhattacharya SK. Effect of polyherbal formulation EuMilon neurochemical perturbations induced by chronic stress. Indian J Exp Biol 2002;40(10):1161-3.
Kulkarni SK, Sharma A, Verma A, et al. GABA receptor mediated anticonvulsant action of Withania somnifera root extract. Indian Drugs 1993;30(7):305-12.
Rastogi R, Mehrotra BN, Compendium of Indian medicinal plants, vol. II, New Delhi: CDRI, Lucknow, Publication and Information Directorate 1993;27.
| Files | ||
| Issue | Vol 54, No 3 (2016) | |
| Section | Original Articles | |
| Keywords | ||
| Withania somnifera Nitric oxide Open field test Forced swimming test Tail suspension test | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
