Phytomedicine
Volume 15, Issue 1 , Pages 2-15 , 25 January 2008

Extracts of Valeriana officinalis L. s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant properties

  • Miguel Hattesohl

      Affiliations

    • Department of Pharmacology and Toxicology, Universitätsklinikum Münster, Westfälische Wilhelms-Universität Münster, Domagkstr. 12, 48149 Münster, Germany
    • Corresponding Author InformationCorresponding author. Tel.:+492518355514; fax: +492518355501.
  • ,
  • Björn Feistel

      Affiliations

    • Finzelberg GmbH & Co. KG, Koblenzer Str. 48-56, 56626 Andernach, Germany
  • ,
  • Hartwig Sievers

      Affiliations

    • PhytoLab GmbH & Co. KG, Dutendorfer Str. 5-7, 91487 Vestenbergsgreuth, Germany
  • ,
  • Romanus Lehnfeld

      Affiliations

    • PhytoLab GmbH & Co. KG, Dutendorfer Str. 5-7, 91487 Vestenbergsgreuth, Germany
  • ,
  • Mirjam Hegger

      Affiliations

    • Department of Pharmacology and Toxicology, Universitätsklinikum Münster, Westfälische Wilhelms-Universität Münster, Domagkstr. 12, 48149 Münster, Germany
  • ,
  • Hilke Winterhoff

      Affiliations

    • Department of Pharmacology and Toxicology, Universitätsklinikum Münster, Westfälische Wilhelms-Universität Münster, Domagkstr. 12, 48149 Münster, Germany

References 

  1. Aktories K, Förstermann U, Hofmann F, Starke K. Allgemeine und spezielle Pharmakologie und Toxikologie. München: Elsevier GmbH; 2005;
  2. Andreatini R, Leite JR. Effect of valepotriates on the behavior of rats in the elevated plus-maze during diazepam withdrawal. Eur. J. Pharmacol. 1994;260(2–3):233–235
  3. Andreatini R, Sartori VA, Seabra ML, Leite JR. Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study. Phytother. Res. 2002;16(7):650–654
  4. Balderer G, Borbely AA. Effect of valerian on human sleep. Psychopharmacology (Berlin). 1985;87(4):406–409
  5. Balduini W, Cattabeni F. Displacement of [3H]-N6-cyclohexyladenosine binding to rat cortical membranes by an hydroalcoholic extract of Valeriana officinalis. Med. Sci. Res. 1989;17:639–640
  6. Bodesheim U, Hölzl J. [Isolation and receptor binding properties of alkaloids and lignans from Valeriana officialis L. Pharmazie. 1997;52(5):386–391
  7. Boissier JR, Simon P. L′utilisation du test de la traction, (Test de JULOU-COURVOISIER) pour l′etude des psycholeptiques. Therapie. 1960;15:1170–1174
  8. Borsini F. Role of the serotonergic system in the forced swimming test. Neurosci. Biobehav. Rev. 1995;19(3):377–395
  9. Cavadas C, Araujo I, Cotrim MD, Amaral T, Cunha AP, Macedo T, et al. In vitro study on the interaction of Valeriana officinalis L. extracts and their amino acids on GABAA receptor in rat brain. Arzneimittelforschung/Drug Res. 1995;45(7):753–755
  10. Committee on Herbal Medicinal Products (HMPC/EMEA). Community Monograph on Valeriana officinalis L, radix, 2006.
  11. Cropley M, Cave Z, Ellis J, Middleton RW. Effect of kava and valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions. Phytother. Res. 2002;16(1):23–27
  12. Dietz BM, Mahady GB, Pauli GF, Farnsworth NR. Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. Brain Res. Mol. Brain Res. 2005;138(2):191–197
  13. Donath F, Quispe S, Diefenbach K, Maurer A, Fietze I, Roots I. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry. 2000;33(2):47–53
  14. Donovan JL, DeVane CL, Chavin KD, Wang JS, Gibson BB, Gefroh HA, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab. Dispos. 2004;32(12):1333–1336
  15. Dorn M. [Efficacy and tolerability of Baldrian versus oxazepam in non-organic and non-psychiatric insomniacs: a randomised, double-blind, clinical, comparative study]. Forsch Komplementarmed Klass Naturheilkd. 2000;7(2):79–84
  16. ESCOP. ESCOP Monographs. Stuttgart: Thieme; 2003;
  17. Fernandez S, Wasowski C, Paladini AC, Marder M. Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis. Pharmacol. Biochem. Behav. 2004;77(2):399–404
  18. Fernandez SP, Wasowski C, Paladini AC, Marder M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur. J. Pharmacol. 2005;512(2–3):189–198
  19. Ferreira F, Santos MS, Faro C, Pires E, Carvalho AP, Cunha AP, et al. Effect of extracts of Valeriana officinalis on [3H]GABA. Rev. Port. Farm. 1996;46(2):74–77
  20. File SE, Mabbutt PS, Hitchcott PK. Characterisation of the phenomenon of “one-trial tolerance” to the anxiolytic effect of chlordiazepoxide in the elevated plus-maze. Psychopharmacology (Berlin). 1990;102(1):98–101
  21. Gerhard U, Linnenbrink N, Georghiadou C, Hobi V. Vigilance-decreasing effects of 2 plant-derived sedatives. Schweiz. Rundsch. Med. Prax. 1996;85(15):473–481
  22. Glass JR, Sproule BA, Herrmann N, Streiner D, Busto UE. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J. Clin. Psychopharmacol. 2003;23(3):260–268
  23. Gries DA, Condouris GA, Shey Z, Houpt M. Anxiolytic-like action in mice treated with nitrous oxide and oral triazolam or diazepam. Life Sci. 2005;76(15):1667–1674
  24. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin. Pharmacol. Ther. 2005;77(5):415–426
  25. Gutierrez S, Ang-Lee MK, Walker DJ, Zacny JP. Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers. Pharmacol. Biochem. Behav. 2004;78(1):57–64
  26. Hall CS. Emotional behavior in the rat: I. Defecation and urination as measures of individual differences in emotionality. J. Comp. Psychol. 1934;18:385–403
  27. Hallam KT, Olver JS, McGrath C, Norman TR. Comparative cognitive and psychomotor effects of single doses of Valeriana officianalis and triazolam in healthy volunteers. Hum. Psychopharmacol. 2003;18(8):619–625
  28. Hendriks H, Bos R, Allersma DP, Malingre TM, Koster AS. Pharmacological screening of valerenal and some other components of essential oil of Valeriana officinalis. Planta Med. 1981;42(1):62–68
  29. Hiller, K.O., Kato, G., 1996. Anxiolytic Activity of Psychotropric Plant Extracts. I. Test of Ethanolic Valeriana Extract STEI Val. Posterpräsentation: 44th Annual Congress of the Society for Medical Plant Research 1996.
  30. Hiller KO, Zetler G. Neuropharmacological studies on ethanol extracts of Valeriana officinalis L.: behavioural and anticonvulsant properties. Phytother. Res. 1996;10:145–151
  31. Kakinohana M, Taira Y, Kakinohana O, Okuda Y. The inhibition of lidocaine metabolism by various barbiturates in rat hepatic microsome. Masui. 1998;47(11):1302–1310
  32. Kamm-Kohl AV, Jansen W. Moderne Baldriantherapie gegen nervöse Störungen. Die Med. Welt. 1984;35:1450–1454
  33. Karcz-Kubicha M, Antoniou K, Terasmaa A, Quarta D, Solinas M, Justinova Z, et al. Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. Neuropsychopharmacology. 2003;28(7):1281–1291
  34. Kuhlmann J, Berger W, Podzuweit H, Schmidt U. The influence of valerian treatment on “reaction time, alertness and concentration” in volunteers. Pharmacopsychiatry. 1999;32(6):235–241
  35. Leathwood PD, Chauffard F, Heck E, Munoz-Box R. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol. Biochem. Behav. 1982;17(1):65–71
  36. Leuschner J, Muller J, Rudmann M. Characterisation of the central nervous depressant activity of a commercially available valerian root extract. Arzneimittelforschung. 1993;43(6):638–641
  37. Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berlin). 1987;92(2):180–185
  38. Mandryk M, Fidecka S, Poleszak E, Malec D. Participation of adenosine system in the ketamine-induced motor activity in mice. Pharmacol. Rep. 2005;57(1):55–60
  39. Marder M, Viola H, Wasowski C, Fernandez S, Medina JH, Paladini AC. 6-methylapigenin and hesperidin: new valeriana flavonoids with activity on the CNS. Pharmacol. Biochem. Behav. 2003;75(3):537–545
  40. Mennini T, Bernasconi P. In vitro study on the interaction of extracts and pure compounds from Valeriana officinalis roots with GABA, benzodiazepine and barbiturate receptors in rat brain. Fitoterapia. 1993;64(4):291–300
  41. Müller CE, Schumacher B, Brattstrom A, Abourashed EA, Koetter U. Interactions of valerian extracts and a fixed valerian–hop extract combination with adenosine receptors. Life Sci. 2002;71(16):1939–1949
  42. Ortiz JG, Nieves-Natal J, Chavez P. Effects of Valeriana officinalis extracts on [3H]flunitrazepam binding, synaptosomal [3H]GABA uptake, and hippocampal [3H]GABA release. Neurochem. Res. 1999;24(11):1373–1378
  43. Ortiz JG, Rassi N, Maldonado PM, Gonzalez-Cabrera S, Ramos I. Commercial valerian interactions with [(3)H]Flunitrazepam and [(3)H]MK-801 binding to rat synaptic membranes. Phytother. Res. 2006;
  44. Patterson JP, Markgraf CG, Cirino M, Bass AS. Validation of a motor activity system by a robotically controlled vehicle and using standard reference compounds. J. Pharmacol. Toxicol. Methods. 2005;52(1):159–167
  45. 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;14(3):149–167
  46. Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977;266(5604):730–732
  47. Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 1978;47(4):379–391
  48. Riedel E, Hansel R, Ehrke G. Inhibition of gamma-aminobutyric acid catabolism by valerenic acid derivatives. Planta Med. 1982;46(4):219–220
  49. Santos MS, Ferreira F, Cunha AP, Carvalho AP, Macedo T. An aqueous extract of valerian influences the transport of GABA in synaptosomes. Planta Med. 1994;60(3):278–279
  50. Santos MS, Ferreira F, Cunha AP, Carvalho AP, Ribeiro CF, Macedo T. Synaptosomal GABA release as influenced by valerian root extract – involvement of the GABA carrier. Arch. Int. Pharmacodyn. Ther. 1994;327(2):220–231
  51. Santos MS, Ferreira F, Faro C, Pires E, Carvalho AP, Cunha AP, et al. The amount of GABA present in aqueous extracts of valerian is sufficient to account for [3H]GABA release in synaptosomes. Planta Med. 1994;60(5):475–476
  52. Schramm E, Hohagen F, Kappler C, Grasshoff U, Berger M. Mental comorbidity of chronic insomnia in general practice attenders using DSM-III-R. Acta Psychiatr. Scand. 1995;91(1):10–17
  53. Schulz H, Jobert M, Hübner WD. The quantitative EEG as a screening instrument to identify sedative effects of single doses of plant extracts in comparison with diazepam. Phytomedicine. 1998;5(6):449–458
  54. Schulz V, Hänsel R. Rationale Phytotherapie. Berlin, Heidelberg, NY: Springer; 2004;
  55. Schumacher B, Scholle S, Holzl J, Khudeir N, Hess S, Muller CE. Lignans isolated from valerian: identification and characterization of a new olivil derivative with partial agonistic activity at A(1) adenosine receptors. J. Nat. Prod. 2002;65(10):1479–1485
  56. Shinomiya K, Fujimura K, Kim Y, Kamei C. Effects of valerian extract on the sleep–wake cycle in sleep-disturbed rats. Acta Med. Okayama. 2005;59(3):89–92
  57. Simmen U, Saladin C, Kaufmann P, Poddar M, Wallimann C, Schaffner W. Preserved pharmacological activity of hepatocytes-treated extracts of valerian and St. John's wort. Planta Med. 2005;71(7):592–598
  58. Vorbach EU, Görteleyer R, Brüning J. Therapie von Insomnien-Wirksamkeit und Verträglichkeit eines Baldrianpräparats. Psychopharmakotherapie. 1996;3(3):109–115
  59. Wagner H, Jurcic K, Schaette R. Comparative studies on the sedative action of Valeriana extracts, valepotriates and their degradation products. Planta Med. 1980;39(4):358–365(authors's translation)
  60. Wasowski C, Marder M, Viola H, Medina JH, Paladini AC. Isolation and identification of 6-methylapigenin, a competitive ligand for the brain GABA(A) receptors, from Valeriana wallichii. Planta Med. 2002;68(10):934–936
  61. Yuan CS, Mehendale S, Xiao Y, Aung HH, Xie JT, Ang-Lee MK. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth. Analg. 2004;98(2):353–358Table of contents
  62. Ziegler G, Ploch M, Miettinen-Baumann A, Collet W. Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia – a randomized, double-blind, comparative clinical study. Eur. J. Med. Res. 2002;7(11):480–486

PII: S0944-7113(07)00294-2

doi: 10.1016/j.phymed.2007.11.027

Phytomedicine
Volume 15, Issue 1 , Pages 2-15 , 25 January 2008