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Planta Med 2012; 78(16): 1719-1724
DOI: 10.1055/s-0032-1315240
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Anxiolytic Properties of Valeriana officinalis in the Zebrafish: A Possible Role for Metabotropic Glutamate Receptors

Lisa M. Del Valle-Mojica
1   Department of Pharmacology and Toxicology, School of Medicine, University of Puerto Rico – Medical Sciences Campus, San Juan, Puerto Rico
,
José G. Ortíz
1   Department of Pharmacology and Toxicology, School of Medicine, University of Puerto Rico – Medical Sciences Campus, San Juan, Puerto Rico
› Author Affiliations
Further Information

Publication History

received 15 January 2012
revised 15 July 2012

accepted 23 July 2012

Publication Date:
24 August 2012 (online)

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Abstract

Valerian extract is used in complementary and alternative medicine for its anxiolytic and sedative properties. Our previous research demonstrated valerian interactions with glutamate receptors. The purpose of this study was to determine if valerian anxiolytic properties are mediated by metabotropic glutamate receptors (mGluR) such as mGluR (1/5) (mGluR I) and mGluR (2/3) (mGluR II). Adult wild-type zebrafish (Danio rerio) prefer the black compartment and avoid the white compartment in the dark/light preference task. Zebrafish exposed to 1 mg/mL of valerian extract or 0.00117 mg/mL valerenic acid increased their residence time in the white side by 84.61 ± 6.55 % and 58.30 ± 8.97 %, respectively. LAP3 (mGluR I antagonist) and EGLU (mGluR II antagonist) significantly inhibited the effects of valerian and valerenic acid. These results demonstrated that valerian and valerenic acid have anxiolytic properties in the zebrafish. Moreover, the selective interaction of valerian with mGluR I and II represent an alternative explanation for the anxiolytic properties of this plant and support the role of mGluR in anxiety.

Key words

zebrafish - Danio rerio - Valeriana officinalis - Valerianaceae - anxiety - valerenic acid - scototaxis

Supporting Information

 

  • References

  • 1 Swanson CJ, Bures M, Johnson MP, Linden AM, Monn JA, Schoepp DD. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 2005; 4: 131-144
    CrossrefPubMedSearch in Google Scholar
  • 2 Tatarczynska E, Klodzinska A, Kroczka B, Chojnacka-Wojcik E, Pilc A. The antianxiety-like effects of antagonists of group I and agonists of group II and III metabotropic glutamate receptors after intrahippocampal administration. Psychopharmacology (Berl) 2001; 158: 94-99
    CrossrefPubMedSearch in Google Scholar
  • 3 Cavaliere C, Rea P, Lynch ME, Blumenthal M. Herbal supplement sales rise in all channels in 2009. Herbal Gram 2010; 86: 62-65
    PubMedSearch in Google Scholar
  • 4 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: 1373-1378
    CrossrefPubMedSearch in Google Scholar
  • 5 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: 191-197
    CrossrefPubMedSearch in Google Scholar
  • 6 Sichardt K, Vissiennon Z, Koetter U, Brattstrom A, Nieber K. Modulation of postsynaptic potentials in rat cortical neurons by valerian extracts macerated with different alcohols: involvement of adenosine A(1)- and GABA(A)-receptors. Phytother Res 2007; 21: 932-937
    CrossrefPubMedSearch in Google Scholar
  • 7 Lacher SK, Mayer R, Sichardt K, Nieber K, Muller CE. Interaction of valerian extracts of different polarity with adenosine receptors: identification of isovaltrate as an inverse agonist at A1 receptors. Biochem Pharmacol 2007; 73: 248-258
    CrossrefPubMedSearch in Google Scholar
  • 8 Del Valle-Mojica LM, Cordero-Hernandez JM, Gonzalez-Medina G, Ramos-Velez I, Berrios-Cartagena N, Torres-Hernandez BA, Ortiz JG. Aqueous and ethanolic Valeriana officinalis extracts change the binding of ligands to glutamate receptors. Evid Based Complement Alternat Med 2011; 2011: 891819
    PubMedSearch in Google Scholar
  • 9 Del Valle-Mojica LM, Ayala-Marin YM, Ortiz-Sanchez CM, Torres-Hernandez BA, Abdalla-Mukhaimer S, Ortiz JG. Selective interactions of Valeriana officinalis extracts and valerenic acid with [H]glutamate binding to rat synaptic membranes. Evid Based Complement Alternat Med 2011; 2011: 40359
    PubMedSearch in Google Scholar
  • 10 Gerlai R, Lahav M, Guo S, Rosenthal A. Drinks like a fish: zebra fish (Danio rerio) as a behavior genetic model to study alcohol effects. Pharmacol Biochem Behav 2000; 67: 773-782
    CrossrefPubMedSearch in Google Scholar
  • 11 Steenbergen PJ, Richardson MK, Champagne DL. The use of the zebrafish model in stress research. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 1432-1451
    CrossrefPubMedSearch in Google Scholar
  • 12 Serra EL, Medalha CC, Mattioli R. Natural preference of zebrafish (Danio rerio) for a dark environment. Braz J Med Biol Res 1999; 32: 1551-1553
    PubMedSearch in Google Scholar
  • 13 Westerfield M. The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio), 5th edition. Eugene: University of Oregon Press; 2007
    Search in Google Scholar
  • 14 Maximino C, Marques de Brito T, Dias CA, Gouveia jr. A, Morato S. Scototaxis as anxiety-like behavior in fish. Nat Protoc 2010; 5: 209-216
    CrossrefPubMedSearch in Google Scholar
  • 15 Conde C, Costa V, Tomaz C. Prostcom: Un conjunto de programas para registro y procesamiento de datos comportamentales en investigación de fisiología y farmacología. Biotemas 2000; 13: 145-159
    PubMedSearch in Google Scholar
  • 16 Mandrekar N, Thakur NL. Significance of the zebrafish model in the discovery of bioactive molecules from nature. Biotechnol Lett 2009; 31: 171-179
    CrossrefPubMedSearch in Google Scholar
  • 17 Crawford AD, Esguerra CV, de Witte PA. Fishing for drugs from nature: zebrafish as a technology platform for natural product discovery. Planta Med 2008; 74: 624-632
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Stewart A, Maximino C, Marques de Brito T, Herculano AM, Gouveia A, Morato S, Cachat JM, Gaikwad S, Elegante MF, Hart PC, Kalueff AV. Neurophenotyping of adult zebrafish using the light/dark box paradigm. In: Kalueff AV, Cachat JM, editors Zebrafish neurobehavioral protocols. Neuromethods, Volume 51. New York: Springer Science; 2011: 157-167
    CrossrefSearch in Google Scholar
  • 19 Maximino C, da Silva AW, Gouveia jr. A, Herculano AM. Pharmacological analysis of zebrafish (Danio rerio) scototaxis. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 624-631
    CrossrefPubMedSearch in Google Scholar
  • 20 Saverino C, Gerlai R. The social zebrafish: behavioral responses to conspecific, heterospecific, and computer animated fish. Behav Brain Res 2008; 191: 77-87
    CrossrefPubMedSearch in Google Scholar
  • 21 Benke D, Barberis A, Kopp S, Altmann KH, Schubiger M, Vogt KE, Rudolph U, Mohler H. GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology 2009; 56: 174-181
    PubMedSearch in Google Scholar
  • 22 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: 537-545
    CrossrefPubMedSearch in Google Scholar
  • 23 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: 399-404
    CrossrefPubMedSearch in Google Scholar
  • 24 Chow NK, Fretz M, Hamburger M, Butterweck V. Telemetry as a tool to measure sedative effects of a valerian root extract and its single constituents in mice. Planta Med 2011; 77: 795-803
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Spinella M. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev 2002; 7: 130-137
    PubMedSearch in Google Scholar
  • 26 Niswender CM, Conn PJ. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010; 50: 295-322
    CrossrefPubMedSearch in Google Scholar
  • 27 Palucha A, Pilc A. Metabotropic glutamate receptor ligands as possible anxiolytic and antidepressant drugs. Pharmacol Ther 2007; 115: 116-147
    CrossrefPubMedSearch in Google Scholar
  • 28 Andreatini R, Leite J. Effect of valepotriates on the behavior of rats in the elevated plus-maze during diazepam withdrawal. Eur J Pharmacol 1994; 260: 233-235
    CrossrefPubMedSearch in Google Scholar
  • 29 Hattesohl M, Feistel B, Sievers H, Lehnfeld R, Hegger M, Winterhoff H. Extracts of Valeriana officinalis L. s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant properties. Phytomedicine 2008; 15: 2-15
    CrossrefPubMedSearch in Google Scholar
  • 30 Murphy K, Kubin ZJ, Shepherd JN, Ettinger RH. Valeriana officinalis root extracts have potent anxiolytic effects in laboratory rats. Phytomedicine 2010; 17: 674-678
    Search in Google Scholar