Journal of Neural Transmission

, Volume 115, Issue 1, pp 35–42 | Cite as

Euphorbia hirta reverses chronic stress-induced anxiety and mediates its action through the GABAA receptor benzodiazepine receptor-Cl channel complex

  • H. Anuradha
  • B. N. Srikumar
  • B. S. Shankaranarayana RaoEmail author
  • M. Lakshmana


Chronic stress is known to result in impairment of learning and memory and precipitate several affective disorders including depression and anxiety. Drugs of natural origin are known to possess several effects on the central nervous system and are emerging as promising alternative therapies. In this context, the hydroalcoholic extract of Euphorbia hirta (Eh) was evaluated for anxiolytic property in chronically stressed rats subjected to elevated plus maze (EPM) and open field test (OFT). Eh treatment (200 mg/kg, p.o.; seven days) showed marked anti-anxiety activity in chronic immobilization stress. In contrast, the forced swim stress-induced anxiety was only partially decreased by Eh. Co-treatment of rats with flumazenil (0.5 mg/kg, i.p.), bicuculline (1 mg/kg, i.p.) or picrotoxin (1 mg/kg, i.p.) resulted in a significant reduction of anxiolytic effect of Eh indicating that its actions are mediated through GABAA receptor-benzodiazepine receptor-Cl channel complex. Thus, our studies indicate that Eh is a potential anxiolytic drug, which might be beneficial in the treatment of stress-induced anxiety disorders.

Keywords: Anxiety; stress; herbal drugs; Euphorbia hirta; elevated plus maze; open field test 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamec, RE, Burton, P, Shallow, T, Budgell, J 1999NMDA receptors mediate lasting increases in anxiety-like behavior produced by the stress of predator exposure – implications for anxiety associated with posttraumatic stress disorderPhysiol Behav65723737PubMedCrossRefGoogle Scholar
  2. Beaubrun, G, Gray, GE 2000A review of herbal medicines for psychiatric disordersPsychiatry Serv5111301134CrossRefGoogle Scholar
  3. Carlini, EA 2003Plants and the central nervous systemPharmacol Biochem Behav75501512PubMedCrossRefGoogle Scholar
  4. Chaki, S, Nakazato, A, Kennis, L, Nakamura, M, Mackie, C, Sugiura, M, Vinken, P, Ashton, D, Langlois, X, Steckler, T 2004Anxiolytic- and antidepressant-like profile of a new CRF1 receptor antagonist, R278995/CRA0450Eur J Pharmacol485145158PubMedCrossRefGoogle Scholar
  5. Chaki, S, Oshida, Y, Ogawa, S, Funakoshi, T, Shimazaki, T, Okubo, T, Nakazato, A, Okuyama, S 2005MCL0042: a nonpeptidic MC4 receptor antagonist and serotonin reuptake inhibitor with anxiolytic- and antidepressant-like activityPharmacol Biochem Behav82621626PubMedCrossRefGoogle Scholar
  6. Ernst, E 2002The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John’s Wort, Ginseng, Echinacea, Saw Palmetto, and KavaAnn Intern Med1364253PubMedGoogle Scholar
  7. Feltenstein, MW, Lambdin, LC, Ganzera, M, Ranjith, H, Dharmaratne, W, Nanayakkara, NP, Khan, IA, Sufka, KJ 2003Anxiolytic properties of Piper methysticum extract samples and fractions in the chick social-separation-stress procedurePhytother Res17210216PubMedCrossRefGoogle Scholar
  8. Ferris, P, Seward, E, Dawson, GR 2001Interactions between LY354740, a group II metabotropic agonist and the GABA(A)-benzodiazepine receptor complex in the rat elevated plus-mazeJ Psychopharmacol157682PubMedCrossRefGoogle Scholar
  9. Galvez, J, Zarzuelo, A, Crespo, ME, Lorente, MD, Ocete, MA, Jimenez, J 1993Antidiarrhoeic activity of Euphorbia hirta extract and isolation of an active flavonoid constituentPlanta Medica59333336PubMedCrossRefGoogle Scholar
  10. Govindarajan, A, Shankaranarayana Rao, BS, Nair, D, Trinh, M, Mawjee, N, Tonegawa, S, Chattarji, S 2006Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effectsProc Natl Acad Sci USA1031320813213PubMedCrossRefGoogle Scholar
  11. Hamner, MB, Robert, S, Frueh, BC 2004Treatment-resistant posttraumatic stress disorder: strategies for interventionCNS Spectr9740752PubMedGoogle Scholar
  12. Heinrichs, SC, De Souza, EB, Schulteis, G, Lapsansky, JL, Grigoriadis, DE 2002Brain penetrance, receptor occupancy and antistress in vivo efficacy of a small molecule corticotropin releasing factor type I receptor selective antagonistNeuropsychopharmacology27194202PubMedCrossRefGoogle Scholar
  13. Johnson, PB, Abdurahman, EM, Tiam, EA, Abdu-Aguye, I, Hussaini, IM 1999Euphorbia hirta leaf extracts increase urine output and electrolytes in ratsJ Ethnopharmacol656369PubMedCrossRefGoogle Scholar
  14. Kienzle-Horn, S 2002Herbal medicines for neurological diseasesCurr Opin Investig Drugs3763767PubMedGoogle Scholar
  15. Kulkarni, SK 1977Open field test: its status in psychopharmacologyIndian J Pharmacol9241246Google Scholar
  16. Langen, B, Egerland, U, Bernoster, K, Dost, R, Unverferth, K, Rundfeldt, C 2005Characterization in rats of the anxiolytic potential of ELB139 [1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-on], a new agonist at the benzodiazepine binding site of the GABAA receptorJ Pharmacol Exp Ther314717724PubMedCrossRefGoogle Scholar
  17. Lanhers, MC, Fleurentin, J, Cabalion, P, Rolland, A, Dorfman, P, Misslin, R, Pelt, JM 1990Behavioral effects of Euphorbia hirta L.: sedative and anxiolytic propertiesJ Ethnopharmacol29189198PubMedCrossRefGoogle Scholar
  18. Lanhers, MC, Fleurentin, J, Dorfman, P, Mortier, F, Pelt, JM 1991Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta Planta Medica57225231PubMedCrossRefGoogle Scholar
  19. McEwen, BS 2000The neurobiology of stress: from serendipity to clinical relevanceBrain Res886172189PubMedCrossRefGoogle Scholar
  20. McEwen, BS 2002The end of stress as we know itNational Academies PressWashington, DCGoogle Scholar
  21. Millan, MJ 2003The neurobiology and control of anxious statesProg Neurobiol7083244PubMedCrossRefGoogle Scholar
  22. Padovan, CM, Del Bel, EA, Guimaraes, FS 2000Behavioral effects in the elevated plus maze of an NMDA antagonist injected into the dorsal hippocampus: influence of restraint stressPharmacol Biochem Behav67325330PubMedCrossRefGoogle Scholar
  23. Pericic, D, Svob, D, Jazvinscak, JM, Mirkovic, KK 2001The involvement of alpha2-adrenoceptors in the anticonvulsive effect of swim stress in micePsychopharmacology (Berl)1588793CrossRefGoogle Scholar
  24. Rao, TL, Kokare, DM, Sarkar, S, Khisti, RT, Chopde, CT, Subhedar, N 2003GABAergic agents prevent alpha-melanocyte stimulating hormone induced anxiety and anorexia in ratsPharmacol Biochem Behav76417423PubMedCrossRefGoogle Scholar
  25. Roche, M, Commons, KG, Peoples, A, Valentino, RJ 2003Circuitry underlying regulation of the serotonergic system by swim stressJ Neurosci23970977PubMedGoogle Scholar
  26. Smith, KK, Dharmaratne, HR, Feltenstein, MW, Broom, SL, Roach, JT, Nanayakkara, NP, Khan, IA, Sufka, KJ 2001Anxiolytic effects of kava extract and kavalactones in the chick social separation-stress paradigmPsychopharmacology (Berl)1558690CrossRefGoogle Scholar
  27. Srikumar, BN, Raju, TR, Shankaranarayana Rao, BS 2006The involvement of cholinergic and noradrenergic systems in behavioral recovery following oxotremorine treatment to chronically stressed ratsNeuroscience143679688PubMedCrossRefGoogle Scholar
  28. Srikumar, BN, Raju, TR, Shankaranarayana Rao, BS 2007Contrasting effects of bromocriptine on learning of a partially baited radial arm maze task in the presence and absence of restraint stressPsychopharmacology (Berl)193363374CrossRefGoogle Scholar
  29. Sunanda, , Shankaranarayana Rao, BS, Raju, TR 2000Chronic restraint stress impairs acquisition and retention of spatial memory task in ratsCurr Sci7915811584Google Scholar
  30. Tona, L, Cimanga, RK, Mesia, K, Musuamba, CT, De Bruyne, T, Apers, S, Hernans, N, Van Miert, S, Pieters, L, Totte, J, Vlietinck, AJ 2004 In vitro antiplasmodial activity of extracts and fractions from seven medicinal plants used in the Democratic Republic of CongoJ Ethnopharmacol932732PubMedCrossRefGoogle Scholar
  31. Tona, L, Kambu, K, Mesia, K, Cimanga, K, Apers, S, De Bruyne, T, Pieters, L, Totte, J, Vlietinck, AJ 1999aBiological screening of traditional preparations from some medicinal plants used as antidiarrhoeal in Kinshasa, CongoPhytomedicine65966Google Scholar
  32. Tona, L, Kambu, K, Ngimbi, N, Mesia, K, Penge, O, Lusakibanza, M, Cimanga, K, De Bruyne, T, Apers, S, Totte, J, Pieters, L, Vlietinck, AJ 2000Antiamoebic and spasmolytic activities of extracts from some antidiarrhoeal traditional preparations used in Kinshasa, CongoPhytomedicine73138PubMedGoogle Scholar
  33. Tona, L, Ngimbi, NP, Tsakala, M, Mesia, K, Cimanga, K, Apers, S, De Bruyne, T, Pieters, L, Totte, J, Vlietinck, AJ 1999bAntimalarial activity of 20 crude extracts from nine African medicinal plants used in Kinshasa, CongoJ Ethnopharmacol68193203CrossRefGoogle Scholar
  34. Vijaya, K, Ananthan, S, Nalini, R 1995Antibacterial effect of theaflavin, polyphenon 60 (Camellia sinensis) and Euphorbia hirta on Shigella spp. – a cell culture studyJ Ethnopharmacol49115118PubMedGoogle Scholar
  35. Vyas, A, Mitra, R, Shankaranarayana Rao, BS, Chattarji, S 2002Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neuronsJ Neurosci2268106818PubMedGoogle Scholar
  36. Wright, IK, Upton, N, Marsden, CA 1992Effect of established and putative anxiolytics on extracellular 5-HT and 5-HIAA in the ventral hippocampus of rats during behaviour on the elevated X-mazePsychopharmacology (Berl)109338346CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • H. Anuradha
    • 1
  • B. N. Srikumar
    • 2
  • B. S. Shankaranarayana Rao
    • 2
    Email author
  • M. Lakshmana
    • 1
  1. 1.Department of PharmacologyGovernment College of PharmacyBangaloreIndia
  2. 2.Department of NeurophysiologyNational Institute of Mental Health and NeurosciencesBangaloreIndia

Personalised recommendations