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

Valle-Mojica, Lisa M. Del; Ortíz, José G.

doi:10.1055/s-0032-1315240

Cited by 22 publications

(13 citation statements)

References 25 publications

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“…For instance, valerian and valerenic acid have anxiolytic properties as tested with the dark/light preference task with zebrafish. This anxiolytic effect of valerian and valerenic acid is abolished after the administration of LAP3 (an mGluR I antagonist) and EGLU (an mGluR II antagonist) [39]. Furthermore, VE has a modest inhibitory effect on 3H dizocilpine (MK-801) binding, an indicator of NMDA-valerian interactions [40].…”

Section: Discussionmentioning

confidence: 99%

Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans

et al. 2017

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Background:Valeriana officinalis extract (VE) is a popular herbal medicine used for the treatment of anxiety and sleep disorders. Although the anxiolytic and sedative effects are mainly attributed to the modulation of GABA-ergic transmission, the mechanism of action has not been fully investigated in humans. Noninvasive brain stimulation protocols can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. In this study, we investigated the effects of a single dose of VE on cortical excitability as assessed with transcranial magnetic stimulation (TMS). Methods: Fifteen healthy volunteers participated in a double-blind, randomized, cross-over, placebo-controlled study. Subjects were required to take either 900 mg of VE (valerenic acid 0.8%) or placebo (an equal dose of vitamin E). Motor cortex excitability was studied by single and paired TMS before and at 1 h and 6 h after the oral administration. Cortical excitability was assessed using different TMS parameters: resting motor threshold, motor-evoked potential amplitude, cortical silent period, short-interval intracortical inhibition, and intracortical facilitation. Furthermore, we assessed sensorimotor integration by short-latency and long-latency afferent inhibition. Results: We found a significant reduction in ICF, without any significant changes in other TMS measures of motor cortex excitability. The amount of ICF returned to baseline value 6 h after the intake of the VE. Conclusion: A single oral dose of VE modulates intracortical facilitatory circuits. Our results in healthy subjects could be predictive markers of treatment response in patients and further support the use of pharmaco-TMS to investigate the neuropsychiatric effects of herbal therapies in humans.

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Section: Discussionmentioning

confidence: 99%

Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans

et al. 2017

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“…Valerenic acid is considered to be the principal constituent [ 29 , 30 ]. The aqueous extract contain hydroxylvalerenic acid and acetoxyvalerenic acid in varying proportions [ 31 , 32 ]. The second objective of the work was to examine the anticonvulsant properties of valerenic acid alone, as well as the aqueous and ethanolic extracts of Valeriana officinalis.…”

Section: Introductionmentioning

confidence: 99%

Valerenic acid and Valeriana officinalis extracts delay onset of Pentylenetetrazole (PTZ)-Induced seizures in adult Danio rerio (Zebrafish)

Torres-Hernández

Valle-Mojica

Ortíz

2015

BMC Complement Altern Med

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BackgroundAnticonvulsant properties have been attributed to extracts of the herbal medicine Valeriana officinalis. Our aims were to examine the anticonvulsant properties of valerenic acid and valerian extracts and to determine whether valerian preparations interact with the activity of other anti-epileptic drugs (phenytoin or clonazepam). To achieve these goals, we validated the adult zebrafish, Danio rerio, as an animal model for studying anticonvulsant drugs.MethodsAll drug treatments were administered by immersion in water containing the drug. For assays of anticonvulsant activity, zebrafish were pretreated with: anti-epileptic drugs, valerenic acid, aqueous or ethanolic valerian extracts, or mixtures (phenytoin or clonazepam with valerenic acid or valerian extracts). Seizures were then induced with pentylenetetrazole (PTZ). A behavioral scale was developed for scoring PTZ-induced seizures in adult zebrafish. The seizure latency was evaluated for all pretreatments and control, untreated fish. Valerenic acid and both aqueous and ethanolic extracts of valerian root were also evaluated for their ability to improve survival after pentylenetetrazole-challenge. The assay was validated by comparison with well-studied anticonvulsant drugs (phenytoin, clonazepam, gabapentin and valproate). One-way ANOVA followed by Tukey post-hoc test was performed, using a p < 0.05 level of significance. All treatments were compared with the untreated animals and with the other pretreatments.ResultsAfter exposure to pentylenetetrazole, zebrafish exhibited a series of stereotypical behaviors prior to the appearance of clonic-like movements—convulsions. Both valerenic acid and valerian extracts (aqueous and ethanolic) significantly extended the latency period to the onset of seizure (convulsion) in adult zebrafish. The ethanolic valerian extract was a more potent anticonvulsant than the aqueous extract. Valerenic acid and both valerian extracts interacted synergistically with clonazepam to extended the latency period to the onset of seizure. Phenytoin showed interaction only with the ethanolic valerian extracts.ConclusionsValerenic acid and valerian extracts have anticonvulsant properties in adult zebrafish. Valerian extracts markedly enhanced the anticonvulsant effect of both clonazepam and phenytoin, and could contribute to therapy of epileptic patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0731-3) contains supplementary material, which is available to authorized users.

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“…With respect to the release of glutamate, we tested the hypothesis that the extracts in the study could act as agonists on mGluRs. In recent years, several studies have investigated the effects of VAL in the excitatory glutamate-mediated neurotransmission and showed that the extract of VAL and in particular valerenic acid are able to interact with Group I and Group II mGluRs, thus having calming and relaxing effects that may represent the main mechanism of action to explain the anxiolytic properties of this plant [21,22,47,48].…”

Section: Discussionmentioning

confidence: 99%

Valeriana Officinalis and Melissa Officinalis Extracts Normalize Brain Levels of GABA and Glutamate Altered by Chronic Stress

Scaglione¹,

Zangara²

2017

J Sleep Disord Manag

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Despite being traditionally used herbals to treat mild anxiety and sleep disorders, Valeriana officinalis and Melissa officinalis mechanism of action is not fully understood. While the pattern of mood modulation of both herbals suggests the involvement of the Gamma-Aminobutyric Acid (GABA) ergic system, other changes in the neurotransmitters pathways can provide an explanation for the clinical effects. The aim of this study was to examine the combined mechanism of action of the two extracts in order to explain the anxiolytic and calming effects that may facilitate sleep induction and improve sleep quality in patients with mild to moderate sleep disturbances. These effects have been previously reported in the literature for a botanical product combining 120 mg Valeriana officinalis and 80 mg of Melissa officinalis standardized extracts (Songha ® Night). To assess mechanism of action we employed the Unpredictable Chronic Mild Stress (UCMS) animal model, as it has strong predictive validity. Brain GABA and glutamate levels were sampled using a microdialysis technique and measured by HPLC. Additional in vitro experiments investigated the effects of the extracts on Group II Metabotropic Glutamate Receptors (mGlu2) binding and GABA Transaminase (GABA-T) activity. Results indicate that the two extracts together exert a functional synergism leading to normalization of brain levels of GABA and glutamate altered by stress. In vitro experiments reveal that the combination of both extracts could inhibit GA-BAT activity more effectively than the single extracts, and that Valeriana officinalis binds mGlu2 receptors. Altogether these results demonstrate a synergistic effect of Valeriana officinalis and Melissa officinalis standardized extracts on counteracting the alterations in neurotransmitter levels caused by chronic stress and support the tranquilizing and sleep inducing activity of Songha ® Night observed in clinical trials.

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

Cited by 22 publications

References 25 publications

<b><i>Valeriana officinalis</i></b> Root Extract Modulates Cortical Excitatory Circuits in Humans

<b><i>Valeriana officinalis</i></b> Root Extract Modulates Cortical Excitatory Circuits in Humans

Valerenic acid and Valeriana officinalis extracts delay onset of Pentylenetetrazole (PTZ)-Induced seizures in adult Danio rerio (Zebrafish)

Valeriana Officinalis and Melissa Officinalis Extracts Normalize Brain Levels of GABA and Glutamate Altered by Chronic Stress

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