Cellular and Molecular Neurobiology

, Volume 34, Issue 4, pp 511–521 | Cite as

Asparagus racemosus Attenuates Anxiety-Like Behavior in Experimental Animal Models

Original Research

Abstract

Asparagus racemosus Linn. (AR) is used worldwide as a medicinal plant. In the present study, the anxiolytic activity of standardized methanolic extract of root of AR (MAR) was evaluated in open-field test (OFT), hole-board, and elevated plus maze (EPM) tests. Rats received oral pretreatment of MAR in the doses of 50, 100, and 200 mg/kg daily for 7 days and then were evaluated for the anxiolytic activity in different animal models. Both MAR (100 and 200 mg/kg) and diazepam (1 mg/kg, p.o.) increased the grooming behavior, number of central squares crossed, and time spent in the central area during OFT. Further, MAR (100 and 200 mg/kg) increased the head-dip and head-dip/sniffing behavior, and decreased sniffing activity in hole-board test. Furthermore, MAR (100 and 200 mg/kg) increased the percentage entries and time spent to open arm in EPM test paradigm. The anxiolytic activity in the experimental models was similar to that of diazepam. MAR (100 and 200 mg/kg) enhanced the level of amygdalar serotonin and norepinephrine. It also increased the expression of 5-HT2A receptors in the amygdala. In another set of experiment, flumazenil attenuated the anxiolytic effect of minimum effective dose of MAR (100 mg/kg) in OFT, hole-board, and EPM tests, indicating GABAA-mediated mechanism. Moreover, the anxiolytic dose of MAR did not show sedative-like effect in OFT and EPM tests compared to diazepam (6 mg/kg, p.o.). Thus, the anxiolytic response of MAR may involve GABA and serotonergic mechanisms. These preclinical data show that AR can be a potential agent for treatment of anxiety disorders.

Keywords

Asparagus racemosus Anxiety Serotonin GABA Amygdala 

Notes

Acknowledgments

DG is thankful to Council of Scientific and Industrial Research (CSIR), India, for student fellowship. SK is thankful to University Grant Commission (UGC), India for the financial support.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Bailey SJ, Toth M (2004) Variability in the benzodiazepine response of serotonin 5-HT1A receptor null mice displaying anxiety-like phenotype: evidence for genetic modifiers in the 5-HT-mediated regulation of GABA(A) receptors. J Neurosci 24:6343–6351CrossRefPubMedGoogle Scholar
  2. Baretta IP, Felizardo RA, Bimbato VF, dos Santos MG, Kassuya CA, Gasparotto A Jr et al (2012) Anxiolytic-like effects of acute and chronic treatment with Achillea millefolium L. extract. J Ethnopharmacol 140:46–54CrossRefPubMedGoogle Scholar
  3. Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248e54CrossRefGoogle Scholar
  4. Bronstein PM (1972) Open field behaviour of the rat as a function of age: cross sectional and longitudinal investigations. J Comp Physiol Psychol 80:335–341CrossRefGoogle Scholar
  5. Carobrez AP, Bertoglio LJ (2005) Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on. Neurosci Biobehav Rev 29:1193–1205CrossRefPubMedGoogle Scholar
  6. Casarrubea M, Sorbera F, Crescimanno G (2009) Structure of rat behavior in hole-board: II) multivariate analysis of modifications induced by diazepam. Physiol Behav 96:683–692CrossRefPubMedGoogle Scholar
  7. Chen H, Zhang L, Rubinow DR, Chuang DM (1995) Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA and binding sites in various regions of the rat hippocampus. Brain Res Mol Brain Res 32:348–353CrossRefPubMedGoogle Scholar
  8. File SE, Wardill AG (1975) The reliability of the holeboard apparatus. Psychopharmacol 44:47–51CrossRefGoogle Scholar
  9. Forchetti CM, Meek JL (1981) Evidence for a tonic GABAergic control of serotonin neurons in the median raphe nucleus. Brain Res 206:208–212CrossRefPubMedGoogle Scholar
  10. Foyet HS, Tsala DE, Bouba AA, Hritcu L (2012) Anxiolytic and antidepressant-like effects of the aqueous extract of Alafia multiflora stem barks in rodents. Adv Pharmacol Sci 2012:912041Google Scholar
  11. Garabadu D, Shah A, Ahmad A, Joshi VB, Saxena B, Palit G et al (2011) Eugenol as an anti-stress agent: modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress. Stress 14:145–155PubMedGoogle Scholar
  12. Goyal RK, Singh J, Lal H (2003) Asparagus racemosus—an update. Ind J Med Sci 57:408–414Google Scholar
  13. Graeff FG, Silveira MC, Nogueira RL, Audi EA, Oliveira RM (1993) Role of the amygdala and periaqueductal gray in anxiety and panic. Behav Brain Res 58:123–131CrossRefPubMedGoogle Scholar
  14. Hale MW, Johnson PL, Westerman AM, Abrams JK, Shekhar A, Lowry CA (2010) Multiple anxiogenic drugs recruit a parvalbumin-containing subpopulation of GABAergic interneurons in the basolateral amygdala. Prog Neuropsychopharmacol Biol Psychiatry 34:1285–1293CrossRefPubMedCentralPubMedGoogle Scholar
  15. Hayes PY, Jahidin AH, Lehmann R, Penman K, Kitching W, De Voss JJ (2008) Steroidal saponins from the roots of Asparagus racemosus. Phytochemistry 69:796–804CrossRefPubMedGoogle Scholar
  16. Hurlemann R, Schlaepfer TE, Matusch A, Reich H, Shah NJ, Zilles K, Maier W, Bauer A (2009) Reduced 5-HT(2A) receptor signaling following selective bilateral amygdala damage. Soc Cogn Affect Neurosci 4:79–84CrossRefPubMedCentralPubMedGoogle Scholar
  17. Jiang X, Xing G, Yang C, Verma A, Zhang L, Li H (2009) Stress impairs 5-HT2A receptor-mediated serotonergic facilitation of GABA release in juvenile rat basolateral amygdala. Neuropsychopharmacol 34:410–423CrossRefGoogle Scholar
  18. Kim C, Speisky MB, Kharouba SN (1987) Rapid and sensitive method for measuring norepinephrine, dopamine, 5-hydroxytriptamine and their major metabolites in rat brain by high-performance liquid chromatography. J Chromatogr 386:25–35CrossRefPubMedGoogle Scholar
  19. Kong WX, Chen SW, Li YL, Zhang YJ, Wang R, Min L, Mi X (2006) Effects of taurine on rat behaviors in three anxiety models. Pharmacol Biochem Behav 83:271–276CrossRefPubMedGoogle Scholar
  20. Krishnamurthy S, Garabadu D, Reddy NR (2013) Asparagus racemosus modulates the hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in rats. Nutr Neurosci 16:255–261Google Scholar
  21. Kumar D, Bhat ZA, Kumar V, Raja W, Shah MY (2013) Anti-anxiety activity of Stachys tibetica Vatke. Chin J Nat Med 11:240–244PubMedGoogle Scholar
  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  23. Mechan AO, Moran PM, Elliott M, Young AJ, Joseph MH, Green R (2002) A comparison between Dark Agouti and Sprague–Dawley rats in their behaviour on the elevated plus-maze, open-field apparatus and activity meters, and their response to diazepam. Psychopharmacol (Berl) 159:188–195CrossRefGoogle Scholar
  24. Meena J, Ojha R, Muruganandam AV, Krishnamurthy S (2011) Asparagus racemosus competitively inhibits in vitro the acetylcholine and monoamine metabolizing enzymes. Neurosci Lett 503:6–9CrossRefPubMedGoogle Scholar
  25. Melo FH, Venâncio ET, de Sousa DP, de França Fonteles MM, de Vasconcelos SM, Viana GS et al (2010) Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission. Fundam Clin Pharmacol 24:437–443CrossRefPubMedGoogle Scholar
  26. Millan MJ (2003) The neurobiology and control of anxious states. Prog Neurobiol 70:83–244CrossRefPubMedGoogle Scholar
  27. Nishikawa T, Scatton B (1983) Evidence for a GABAergic inhibitory influence on serotonergic neurons originating from the dorsal raphe. Brain Res 279:325–329CrossRefPubMedGoogle Scholar
  28. Ojha R, Sahu AN, Muruganandam AV, Singh GK, Krishnamurthy S (2010) Asparagus recemosus enhances memory and protects against amnesia in rodent models. Brain Cogn 74:1–9CrossRefPubMedGoogle Scholar
  29. Palkovits M, Brownstein MJ (1988) Maps and guide to microdissection of the rat brain. Elsevier, New YorkGoogle Scholar
  30. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167CrossRefPubMedGoogle Scholar
  31. Pompeiano M, Palacios JM, Mengod G (1994) Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Brain Res Mol Brain Res 23:163–178CrossRefPubMedGoogle Scholar
  32. Ramanathan M, Jaiswal AK, Bhattacharya SK (1998) Differential effects of diazepam on anxiety in streptozotocin induced diabetic and non-diabetic rats. Psychopharmacol (Berl) 135:361–367CrossRefGoogle Scholar
  33. Ripoll N, Hascoët M, Bourin M (2006) Implication of 5-HT2A subtype receptors in DOI activity in the four-plates test-retest paradigm in mice. Behav Brain Res 166:131–139CrossRefPubMedGoogle Scholar
  34. Sairam K, Priyambada S, Aryya NC, Goel RK (2003) Gastroduodenal ulcer protective activity of Asparagus racemosus: an experimental, biochemical and histological study. J Ethnopharmacol 86:1–10CrossRefPubMedGoogle Scholar
  35. Sharma PC, Yelne MB, Dennis TJ (2000) Database on medicinal plants used in Ayurveda, volume I. Central Council for Research in Ayurveda and Siddha. Yugantar Prakashan (P.) Ltd., New Delhi, pp 418–430Google Scholar
  36. Sharma U, Kumar N, Singh B (2012) Furostanol saponin and diphenylpentendiol from the roots of Asparagus racemosus. Nat Prod Commun 7:995–998PubMedGoogle Scholar
  37. Singh GK, Garabadu D, Muruganandam AV, Joshi VK, Krishnamurthy S (2009) Antidepressant activity of Asparagus racemosus in rodent models. Pharmacol Biochem Behav 91:283–290CrossRefPubMedGoogle Scholar
  38. Somania R, Singhai AK, Shivgunde P, Jain D (2012) Asparagus racemosus Willd (Liliaceae) ameliorates early diabetic nephropathy in STZ induced diabetic rats. Ind J Exp Biol 50:469–475Google Scholar
  39. Spannuth BM, Hale MW, Evans AK, Lukkes JL, Campeau S, Lowry CA (2011) Investigation of a central nucleus of the amygdala/dorsal raphe nucleus serotonergic circuit implicated in fear-potentiated startle. Neuroscience 179:104–119CrossRefPubMedCentralPubMedGoogle Scholar
  40. Strohle A, Holsboer F (2003) Stress responsive neurohormones in depression and anxiety. Pharmacopsychiatry 36:S207–S214CrossRefPubMedGoogle Scholar
  41. Wall PM, Messier C (2001) Methodological and conceptual issues in the use of the elevated plus-maze as a psychological measurement instrument of animal anxiety-like behavior. Neurosci Biobehav Rev 25:275–286Google Scholar
  42. Weisstaub NV, Zhou M, Lira A, Lambe E, González-Maeso J, Hornung JP, Sibille E, Underwood M, Itohara S, Dauer WT, Ansorge MS, Morelli E, Mann JJ, Toth M, Aghajanian G, Sealfon SC, Hen R, Gingrich JA (2006) Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Science 313:536–540CrossRefPubMedGoogle Scholar
  43. Xu T, Pandey SC (2000) Cellular localization of serotonin (2A) (5HT (2A)) receptors in the rat brain. Brain Res Bull 51:499–505CrossRefPubMedGoogle Scholar
  44. You JS, Peng M, Shi JL, Zheng HZ, Liu Y, Zhao BS, Guo JY (2012) Evaluation of anxiolytic activity of compound Valeriana jatamansi Jones in mice. BMC Complement Altern Med 12:223CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Neurotherapeutics Lab, Department of PharmaceuticsIndian Institute of Technology (Banaras Hindu University)VaranasiIndia

Personalised recommendations