RESUMEN
Valeriana officinalis (valerian) is used traditionally as a mild sedative. Research into valerian is sparse, and studies differ greatly with respect to design, measures and preparations used. This study compares the action of a methanol (M-E), ethanol (E-E) and an extract macerated with ethylacetate (EA-E) from roots of valerian (Valeriana officinalis L., Valerianaceae) on postsynaptic potentials (PSPs) in cortical neurons. Intracellular recordings were performed in rat brain slice preparations containing pyramidal cells of the cingulate cortex. PSPs were induced by electrical field stimulation. The M-E induced strong inhibition in the concentration range 0.1-15 mg/mL, whereas the E-E (1-10 mg/mL) did not influence significantly the PSPs. The maximum inhibition induced by the M-E was completely antagonized by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microm), an antagonist on the adenosine A(1) receptor. Contrary to the M-E, the EA-E (10 mg/mL) induced an increase of the PSPs, which was completely blocked by the GABA(A) receptor antagonist picrotoxin (100 microm). The data suggest that activation of adenosine A(1) and GABA(A) receptors is mediated by different components within the valerian extract. The two mechanisms may contribute independently to the sleep-inducing effect of valerian.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Neuronas/efectos de los fármacos , Receptor de Adenosina A1/fisiología , Receptores de GABA-A/fisiología , Transmisión Sináptica/efectos de los fármacos , Valeriana/química , Animales , Corteza Cerebral/citología , Etanol/química , Masculino , Potenciales de la Membrana/efectos de los fármacos , Metanol/química , Neuronas/fisiología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Ratas , Ratas WistarRESUMEN
Valerian and hops are traditionally used as sleep aids. Since the fixed extract combination (Ze 91019) as a whole is considered the active compound, the clinical efficacy must be demonstrated for this extract combination. The present clinical study aimed to demonstrate superiority of the fixed extract combination in comparison with placebo in patients suffering from non-organic insomnia (ICD 10, F 51.0-51.2). Objective sleep parameters were registered by means of a transportable home recorder system (QUISI). The primary outcome was the reduction in sleep latency (SL2) which had to be prolonged at baseline (>/=30 min) as an inclusion criteria. The treatment period lasted for 4 weeks with either placebo, single valerian extract (Ze 911) or the fixed valerian hops extract combination (Ze 91019). The amount of the single valerian extract was identical to that amount contained in the fixed extract combination, i.e. 500 mg valerian extract siccum. In the extract combination 120 mg hops extract siccum was added. Both the extracts were prepared with 45% methanol m/m with a drug-extract ratio of 5.3:1 (valerian) and 6.6:1 (hops), respectively. The fixed extract combination was significantly superior to the placebo in reducing the sleep latency whilst the single valerian extract failed to be superior to the placebo. The result underlined the plausibility for adding hops extract to the valerian extract.
Asunto(s)
Humulus , Hipnóticos y Sedantes/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Valeriana , Administración Oral , Adulto , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Extractos Vegetales/administración & dosificación , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Due to the electrochemical nature of the communication structure of the brain an intimate relationship between neurotransmitter activity on one side and field potentials (EEG) on the other side have been reported. From this it can be assumed that the electrical activity reflects the net effect of drug action. The influence of increasing doses of Ze 91019 on field potentials in chronically instrumented, freely moving rats was registered for 4 hours in order to test its action on the central nervous system. Doses of 200 mg and 250 mg valerian siccum extract (with additional 48 or 60 mg hop siccum extract) increased the spectral power in the delta, theta and alpha frequency bands of the frontal cortex suggestive of attenuated cholinergic transmission. Since adenosine administration into the basal forebrain also increases the low frequency activity in the frontal cortex it can be assumed that adenosine in the basal forebrain mediates these frequency changes by attenuating the frontal cholinergic system. Thus, Valerian and the fixed valerian hop extract combination Ze 91019 seems to cause this change of spectral power acting as an adenosine A1 receptor agonist. The results are therefore in line with the view that the fixed extract combination Ze 91019 works as an adenosine agonist via inhibition of cholinergic transmission leading to sedation and sleep.
Asunto(s)
Electroencefalografía/efectos de los fármacos , Lóbulo Frontal/efectos de los fármacos , Humulus , Extractos Vegetales/administración & dosificación , Valeriana , Administración Oral , Animales , Combinación de Medicamentos , Lóbulo Frontal/metabolismo , Hipocampo/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Receptores Colinérgicos/metabolismo , Receptores Purinérgicos P1/metabolismoRESUMEN
In this study we evaluated the adenosine A1 receptor-mediated effect of valerian extract (Ze 911) on postsynaptic potentials (PSPs) in pyramidal cells of the rat cingulate cortex in a slice preparation. We first observed that N6-cyclopentyladenosine (CPA, 0.01 - 10 microM), an adenosine A1 receptor agonist, inhibited PSPs in a concentration-dependent manner. The CPA (10 microM)-induced inhibition was antagonized by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microM), an adenosine A1 receptor antagonist. Ze 911 concentration dependently (0.1 - 15 mg/mL) inhibited PSPs in the presence of the adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC, 0.2 microM) and adenosine deaminase (1 U/mL). The maximal inhibition induced by 10 mg/mL was completely antagonised by DPCPX (0.1 microM), an A1 receptor blocker. The data suggest that activation of adenosine A1 receptors is involved in the pharmacological effects of the valerian extract Ze 911.
Asunto(s)
Potenciales Postsinápticos Excitadores/efectos de los fármacos , Extractos Vegetales/farmacología , Células Piramidales/efectos de los fármacos , Receptor de Adenosina A1/efectos de los fármacos , Valeriana , Agonistas del Receptor de Adenosina A1 , Animales , Giro del Cíngulo/citología , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Células Piramidales/fisiología , Ratas , Ratas WistarRESUMEN
The aim of the study was to demonstrate competition between caffeine and a fixed valerian/hop extract combination (Ze91019) by the central adenosine mechanism. EEG was used to describe the action of caffeine on the central nervous system after oral administration (200 mg) in healthy volunteers. In addition to caffeine, the volunteers (16 in each group) received either placebo or verum (2 and 6 tablets containing the valerian/hop extract). The EEG responses were recorded every 30 min thereafter. The verum medication was capable of reducing (2 tablets) or inhibiting (6 tablets) the arousal induced by caffeine. This pharmacodynamic action was observed 60 minutes after oral administration, indicating not only competition between the antagonist caffeine and the partial agonist, i. e., the valerian/hop extract but also bio-availability of the compound(s) responsible for the agonistic action. In conclusion, the valerian/hop extract acts via a central adenosine mechanism which is possibly the reason for its sleep-inducing and -maintaining activity.
Asunto(s)
Humulus , Fitoterapia , Extractos Vegetales/farmacología , Receptor de Adenosina A2A/efectos de los fármacos , Valerianaceae , Administración Oral , Adulto , Cafeína/administración & dosificación , Cafeína/farmacología , Sistema Nervioso Central/efectos de los fármacos , Electroencefalografía , Humanos , Masculino , Extractos Vegetales/administración & dosificación , Raíces de PlantasRESUMEN
The fixed valerian-hops extract combination Ze91019 is used as a sleep aid. Although its exact mechanism of action is not well understood, earlier studies indicate that the CNS effect of valerian might occur through interaction with the GABA, melatonin and/or the adenosine systems in the brain. The use of hops in sleep remedies, however, is mainly based on traditional use and scarce scientific information. In this report, the binding of Ze91019, and the component valerian and hops extracts within, was tested on 14 subtypes of five classes of central receptors (dopamine, serotonin, melatonin, MCH and neuropeptide-Y). Binding affinities could be demonstrated at some of the screened melatonin (ML1 and ML2) and serotonin (5-HT4e, 5-HT6 and 5-HT7) receptor subtypes.