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PubMed1992

Psychotropic effects of Japanese valerian root extract.

The psychotropic effects of "Hokkai-Kisso", i.e. roots of Japanese valerian, were compared with those of diazepam and imipramine. Both 30% EtOH extract of valerian root (11.2 g/kg) and diazepam (3 mg/kg) significantly prolonged hexobarbital-induced sleep in mice. Spontaneous ambulation and rearing during an open field test were significantly decreased by valerian extract (11.2 g/kg), but kessyl glycol diacetate (KGD, 400 mg/kg) and diazepam (3 mg/kg) significantly increased ambulation. Diazepam (10 mg/kg) significantly decreased approach-avoidance conflict in mice in a water-lick conflict test, but valerian extract and KGD did not. By contrast, valerian extract (4.1 g/kg) and imipramine (20 mg/kg) significantly inhibited immobility induced by a forced swimming test in rats, but did not increase spontaneous motor activity during an open field test just before the forced swimming test. In addition, valerian extract and imipramine significantly reversed reserpine-induced hypothermia in mice. These results indicate that valerian extract acts on the central nervous system and may be an antidepressant.

Animals↗
PubMed2002

Effect of kava and valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions.

This study investigated whether kava or valerian could moderate the effects of psychological stress induced under laboratory conditions in a group of healthy volunteers. Fifty-four participants performed a standardized colour/word mental stress task on two occasions 1 week apart. Blood pressure (BP), heart rate (HR) and subjective ratings of pressure were assessed at rest and during the mental stress task. Following the first session (time 1 = T1), individuals took a standard dose of kava (n = 18), or valerian (n = 18) for 7 days, while the remainder acted as controls (n = 18). Differences in BP and HR from resting levels were calculated as reactions to the stress task at both time points. At the second session (time 2 = T2) there was a significant decrease in systolic BP responsivity in both the kava and valerian groups relative to T1, but there were no significant reductions in diastolic BP. Between T1 and T2, the HR reaction to mental stress was found to decline in the valerian group but not in the kava group. Individuals taking kava or valerian reported less pressure during the task at T2 relative to T1. There were no significant differences in BP, HR or subjective reports of pressure between T1 and T2 in the controls. Behavioural performance on the colour/word task did not change between the groups over the two time points. The results suggest that kava and valerian may be beneficial to health by reducing physiological reactivity during stressful situations.

Adolescent↗
PubMed1982

Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man.

The effect of an aqueous extract of valerian (Valeriana officinalis L.) root on subjectively rated sleep measures was studied on 128 people. Each person received 9 samples to test (3 containing placebo, 3 containing 400 mg valerian extract and 3 containing a proprietary over-the-counter valerian preparation). The samples, identified only by a code number, and presented in random order, were taken on non-consecutive nights. Valerian produced a significant decrease in subjectively evaluated sleep latency scores and a significant improvement in sleep quality: the latter was most notable among people who considered themselves poor or irregular sleepers, smokers, and people who thought they normally had long sleep latencies. Night awakenings, dream recall and somnolence the next morning were relatively unaffected by valerian. With the proprietary valerian-containing preparation, the only change was a significant increase in reports of feeling more sleepy than normal the next morning. Thus the questionnaire, simple to use and non-invasive, provides a sensitive means for detecting the effects of mild sedatives on different aspects of sleep in man. It also allows identification within the test population of the subgroups most affected.

Adult↗
PubMed2003

Analysis of responses to valerian root extract in the feline pulmonary vascular bed.

OBJECTIVES: This study was undertaken to investigate pulmonary vascular response to valerian (Valeriana officinalis) in the feline pulmonary vasculature under constant flow conditions. DESIGN: In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an adenosine triphosphate (ATP)-sensitive potassium (K+) channel blocker, meclofenamate, a nonselective cyclooxygenase (COX) inhibitor, bicuculline, a GABA(A) receptor antagonist, and saclofen, a GABA(B) antagonist, were investigated on pulmonary arterial responses to various agonists in the feline pulmonary vascular bed. These agonists included valerian, muscimol, a GABA(A) agonist, SKF-97541 a GABA(B) agonist, acetylcholine (ACh), and bradykinin, both inducers of nitric oxide synthase, arachidonic acid, a COX substrate, and pinacidil, an ATP-sensitive K+ channel activator, during increased tone conditions induced by the thromboxane A2 mimic, U46619. SETTINGS/LOCATION: Laboratory investigation. SUBJECTS: Mongrel cats of either gender. INTERVENTIONS: Injections of the abovementioned agonists and antagonists were given. OUTCOME MEASURES: Baseline pulmonary tone, responses to the agonists, and responses to the agonists after injections of antagonists were all measured via a pulmonary catheter transducer and recorded. RESULTS: Valerian root extract is a potent smooth muscle dilator in the feline pulmonary vascular bed. The vasodilatory effects of valerian root extract were unchanged after the administration of L-NIO, glibenclamide, and meclofenamate. These effects were ablated, however, by both saclofen and bicuculline. The ability of saclofen and bicuculline to modulate the dilatory effects of valerian root extract was not statistically different. CONCLUSIONS: The vasodilatory effects of valerian root extract are mediated by a nonselective GABA mechanism.

Acetylcholine↗
PubMed2004

In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4.

PURPOSE: Valerian root ( Valeriana officinalis L.) has been used since antiquity as a medicinal herb. Recent studies have found that certain herbal products used concomitantly with conventional therapeutic products can markedly affect drug disposition. METHODS: The in vitro effect of aliquots from 14 commercially available single-entity and blended products containing valerian root on cytochrome P450 CYP3A4-mediated metabolism and P-glycoprotein transport has been determined with aqueous, ethanol and acetonitrile extracts. RESULTS: Hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid content was analyzed and wide variation was found between samples and compared to the concentrations noted on the product labels. Valerian extracts from the products tested also exhibited a marked capacity to inhibit cytochrome P450 3A4-mediated metabolism and P-glycoprotein transport based upon the ATPase assay. CONCLUSIONS: There is wide variation between commercially available samples of valerian root. The findings from this study suggest that valerian root may have an initial inhibitory effect when taken with therapeutic products. Further work is warranted to determine whether valerian root can affect other CYP450 isozymes and how the results of this in vitro investigation can be extrapolated to in vivo situations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Exposure to airborne microorganisms, dust and endotoxin during processing of valerian roots on farms.

The aim of this study was to determine the levels of microorganisms, dust and endotoxin in the air during various stages of valerian (Valeriana officinalis) roots processing by herb farmers and to examine the species composition of airborne microflora. Air samples were collected on glass fibre filters by use of personal samplers on 15 farms owned by valerian cultivating farmers, located in Lublin province (eastern Poland). The concentrations of total viable microorganisms (bacteria + fungi) in the air showed a marked variability and were within a range of 0.95-7,966.6 x 10(3) cfu/m (3). Though median was relatively low (10.75 x 10(3) cfu/m (3)), on 4 farms the concentrations exceeded the level of 10(5) cfu/m (3) and on 1 farm the level of 10(6) cfu/m (3). During the processing of valerian roots, distinct changes could be observed in the composition of airborne microflora. In the first stages of processing, the freshly dug and washed roots until shaking in the drying room, the most numerous were Gram-negative bacteria of the family Pseudomonadaceae (mostly Stenotrophomonas maltophilia, Pseudomonas chlororaphis and Pseudomonas fluorescens). After drying, the dominant organisms were thermo-resistant endospore-forming bacilli (Bacillus spp.) and fungi, among which prevailed Aspergillus fumigatus. Altogether, 29 species or genera of bacteria and 19 species or genera of fungi were identified in the farm air during valerian processing, of these, 10 and 12 species or genera respectively were reported as having allergenic and/or immunotoxic properties. The concentrations of airborne dust and endotoxin on the examined farms were very large and ranged from 10.0-776.7 mg/m (3), and from 0.15-24,448.2 microg/m (3), respectively (medians 198.3 mg/m (3) and 40.48 microg/m (3)). In conclusion, farmers cultivating valerian could be exposed during processing of valerian roots to large concentrations of airborne microorganisms, dust and endotoxin posing a risk of work-related respiratory disease.

Agricultural Workers' Diseases↗
PubMed2001

Stress-induced insomnia treated with kava and valerian: singly and in combination.

Kava and valerian are herbal remedies that are claimed to have anxiolytic and sedative properties respectively, without dependence potential or any appreciable side effects. In this pilot study, 24 patients suffering from stress-induced insomnia were treated for 6 weeks with kava (LI-150), 120 mg daily. This was followed by a 2-week 'wash-out' period off treatment, and then, five patients having dropped out, 19 received valerian (LI-156), 600 mg daily, for another 6 weeks. Then there was a further 2-week period off treatment, and a final 6 weeks of treatment of these 19 patients with the two compounds combined (kava + valerian). Stress was measured in three areas: social, personal and life events; insomnia in three areas also: time to fall asleep, hours slept and waking mood. Total stress severity was significantly relieved by both compounds individually (p < 0.01), with no significant differences between them; and there was also improvement with the combination, significant in the case of insomnia (p < 0.05). On direct questioning, 16 patients (67%) reported no side effects on kava, 10 (53%) on valerian and 10 (53%) on the combination. The 'commonest' effect was vivid dreams with kava + valerian (4 cases (21%)) and with valerian alone (3 cases (16%)), followed by gastric discomfort and dizziness with kava (3 cases each (3 %)). These results are considered to be extremely promising but further studies may be required to determine the relative roles of the two compounds for such indications. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2001

The use of valerian in neuropsychiatry.

Valerian is a medicinal agent deriving from the plant Valeriana officinalis L. We reviewed the available literature on the use of valerian preparations in the treatment of neuropsychiatric disorders. Preclinical studies suggest that valerian has sedative and muscle-relaxant effects. Few clinical trials with valerian have been carried out in conditions other than insomnia. The insomnia studies have methodologic shortcomings but suggest that some preparations lead to significant subjective improvement in sleep complaints with remarkably few side effects. Furthermore, some evidence indicates that valerian preparations may have a mechanism of action and clinical characteristics that differ from the benzodiazepine-related sedative/hypnotics, making them more suitable for long-term use. If this safety profile and the plant's sedative/hypnotic efficacy are confirmed in double-blind, placebo-controlled trials with carefully and consistently prepared valerian compounds, then those compounds would fill an important and presently unfilled niche in the treatment of insomnia.

Journal Article↗
PubMed2006

Valerian for sleep: a systematic review and meta-analysis.

Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety.

Humans↗
PubMed2006

Studies on the cytological and biochemical effects of valerian in somatic and germ cells of Swiss albino mice.

Valerian is widely known for its use as a sedative and an anti-anxiety drug in the folk medicine. Literature reports suggested valerian to induce genotoxicity in vitro (ECV304 cells) by reactive oxygen species-mediated mechanism; however, there are no reports on its genotoxicity and/or the epigenetic mechanism in vivo. In view of the folkloric significance, it was found worthwhile to (1) determine the genotoxic effects of valerian in somatic and germ cells of mice and (2) investigate the role of epigenetic mechanisms. The protocol included the oral treatment of mice with different doses (500, 1000 and 2000 mg/kg/day) of valerian for 7 days. The following experiments were conducted: (i) cytological studies on micronucleus test, (ii) cytogenetic analysis for meiotic chromosomes, (iii) cytological analysis of spermatozoa abnormalities, (iv) quantification of proteins and nucleic acids in testicular cells and (v) estimation of malondialdehyde (MDA) and nonprotein sulfhydryl (NP-SH) in hepatic and testicular cells. The treatment increased the frequency of micronuclei in the polychromatic erythrocytes (PCE) and decrease the ratio of PCE to normochromatic erythrocytes (NCE) in the femur. It caused aberrations in chromosomes of the testis and induced spermatozoa abnormalities. The concentration of nucleic acids was depleted in the testicular cells. These changes might be attributed to the epigenetic mechanisms as revealed by an increase in the concentrations of MDA and a decrease of NP-SH levels in hepatic and testicular cells observed in the present study. The observed changes may be ascribed to terpenoids (valepotriates) and flavonoids (6-methylapigenin and 2S(-)-hesperidin) present in valerian.

Administration, Oral↗
PubMed2003

Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-1 trials.

OBJECTIVE: To investigate the effectiveness of valerian for the management of chronic insomnia in general practice. DESIGN: Valerian versus placebo in a series of n-of-1 trials, in Queensland, Australia. RESULTS: Of 42 enrolled patients, 24 (57%) had sufficient data for inclusion into the n-of-1 analysis. Response to valerian was fair for 23 (96%) participants evaluating their "energy level in the previous day" but poor or modest for all 24 (100%) participants' response to "total sleep time" and for 23 (96%) participants' response to "number of night awakenings" and "morning refreshment". As a group, the proportion of treatment successes ranged from 0.35 (95% CI 0.23, 0.47) to 0.55 (95% CI 0.43, 0.67) for the six elicited outcome sleep variables. There was no significant difference in the number (P=0.06), distribution (P=1.00) or severity (P=0.46) of side effects between valerian and placebo treatments. CONCLUSIONS: Valerian was not shown to be appreciably better than placebo in promoting sleep or sleep-related factors for any individual patient or for all patients as a group.

Adult↗
PubMed2003

Investigation of the effects of peppermint oil and valerian on rat liver and cultured human liver cells.

1. The aim of the present study was to investigate the effects of peppermint oil and valerian on rat liver and cultured human hepatoma cells. 2. Rats received a single oral dose of peppermint oil (8.3-830 microL/kg) or valerian (0.31-18.6 g/kg), or daily oral doses of 83 microL/kg peppermint oil or 3.1 g/kg valerian for 28 days. After 24 h, rats were anaesthetized and measurements made of bile flow, liver function and in vivo sinusoidal area. Livers were then removed for histology. 3. Bile flow was unaffected by any treatment, except acute high-dose peppermint oil (830 microL/kg; 70% increase in flow). No change in liver enzyme activity was found, except for a 45% increase in alkaline phosphatase after chronic peppermint oil. No change in sinusoidal area in vivo or in histology was found following any treatment, although pretreatment with carbon tetrachloride reduced sinusoidal bed area and produced histological damage. Incubation of human hepatoma cells with 0.5 microL/mL (but not 0.05 microL/mL) peppermint oil or 20 mg/mL (but not 2 mg/mL) valerian resulted in increased cell death. 4. In conclusion, the present study demonstrated in vitro toxicity of high doses of valerian and peppermint oil in cultured human hepatoma cells and, at doses 2-3 orders of magnitude greater than those recommended for human use, an increase in rat bile flow after acute peppermint oil and an increase in alkaline phosphatase after chronic peppermint oil.

Animals↗
PubMed2002

Effect of valerian, Valeriana edulis, on sleep difficulties in children with intellectual deficits: randomised trial.

Serious sleep problems are common in children with an intellectual deficit (ID), and are often the source of much distress for both the child and caregivers. As yet, no satisfactory long-term treatment exists for intransigent sleep difficulties in children with an ID. Valerian, Valeriana spp., has been used for thousands of years to induce relaxation and sleep. Scientific investigation of valerian's sleep promoting ability in humans, whilst limited, has yielded promising findings. This initial study aimed to explore valerian's potential for assisting in the treatment of sleep problems in children with an ID. Five children with varying intellectual deficits and different primary sleep problems underwent eight continuous weeks of monitoring via sleep diaries, adhering to a double blind, placebo controlled and randomised design. Compared to baseline and placebo, valerian treatment led to significant reductions in sleep latencies and nocturnal time awake, lengthened total sleep time and improved sleep quality. The treatment was apparently most effective in children with deficits that involved hyperactivity. Although the findings are preliminary and in need of replication, there is evidence to suggest that valerian may be useful in the safe and effective long-term treatment of intransigent sleep difficulties in children with ID's, and therefore warrants further investigation.

Administration, Oral↗
PubMed2005

Effects of valerian extract on the sleep-wake cycle in sleep-disturbed rats.

The present study was performed to investigate the effects of valerian extract on the sleep-wake cycle using sleep-disturbed model rats. A significant shortening in sleep latency was observed with valerian extract at doses of 1000 and 3000 mg/kg. On the other hand, valerian extract had no significant effects on total times of wakefulness, non-rapid eye movement (non-REM) sleep, or REM sleep, even at a dose of 3000 mg/kg. Valerian extract at doses of 1000 and 3000 mg/kg showed a significant increase in the delta activity during non-REM sleep. In conclusion, valerian extract may be useful as an herbal medicine having not only sleep-inducing effects but also sleep quality-enhancement effects.

Animals↗
PubMed2000

Pharmacodynamic effects of valerian and hops extract combination (Ze 91019) on the quantitative-topographical EEG in healthy volunteers.

The aim of this investigation was to objectify the pharmacodynamic effects of different dosages of a commercially available plant extract mixture of valerian and hops by means of the quantitative topographical EEG (qEEG) in healthy young adults in comparison to placebo. Two different dosages were applied in two single-blind, cross-over designed observation trials in 12 healthy volunteers (1st dosage: 500 mg valerian and 120 mg hops, versus placebo, first clinical trial; 2nd dosage: 1500 mg valerian and 360 mg hops, versus placebo, second clinical trial). QEEG was recorded bipolarly from 17 surface electrodes according to the 10:20 system and analysed using the Fast Fourier Transformation prior to, 1, 2 and 4 hours after drug intake in the recording conditions eyes open, eyes closed and under mental demand. The EEG-spectra were cut into six frequency bands. Both resting conditions (eyes open and eyes closed) were analysed together. After application of the low dosage qEEG power changes remained more or less within placebo range following the normal circadian rhythmics, except for a tendentious reduction of alpha- and beta1-power 4 h after drug intake. The high dosage led to power increases in delta, decreases in alpha and a weak decrease in beta-power. Under mental performance only weak differences to placebo were seen which are not discussed here. In the CPT (completion of complicated additions and subtractions) the concentration and performance capability were hardly influenced. However, a minimal increase of mean answer time and mean OK time (time for correct answers) was observed 4 hours after intake of 2 dragees and 1 hour after 6 dragees of valerian and hops mixture with more pronounced changes after the low dosage than the high one. In summary, the quantitative topographical EEG was able to show slight, but clear visible effects on the CNS especially after intake of the high dosage of valerian-hops mixture Ze 91019 indicating reproducible pharmacodynamic responses of the target organ.

Administration, Oral↗
PubMed2002

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.

Patients aged 18 to 73 years and diagnosed with non-organic insomnia according to ICD-10 (F 51.0) were treated in a multicentre, double-blind, randomised parallel group comparison with either 600 mg/die valerian extract LI 156 (Sedonium) or 10 mg/die oxazepam taken for 6 weeks. A total of 202 outpatients with a mean duration of insomnia of 3.5 months at baseline were included at 24 study centres (general practices) in Germany. - Sleep quality (SQ) after 6 weeks measured by the Sleep Questionnaire B (SF-B; CIPS 1996) showed that 600 mg/die valerian extract LI 156 was at least as efficacious as a treatment with 10 mg/die oxazepam. Both treatments markedly increased sleep quality compared with baseline (p <0.01). The other SF-B subscales, i.e. feeling of refreshment after sleep (GES), psychic stability in the evening (PSYA), psychic exhaustion in the evening (PSYE), psychosomatic symptoms in the sleep phase (PSS), dream recall (TRME), and duration of sleep confirmed similar effects of both treatments. Clinical Global Impressions scale (CGI) and Global Assessment of Efficacy by investigator and patient, again, showed similar effects of both treatments. Adverse events occurred in 29 patients (28.4%) receiving valerian extract LI 156 and 36 patients (36.0%) under oxazepam, and were all rated mild to moderate. No serious adverse drug reactions were reported in either group. Most patients assessed their respective treatment as very good (82.8% in the valerian group, 73.4% in the oxazepam group). During the 6 week treatment phase Valerian extract LI 156 (Sedonium) 600 mg/die showed a comparable efficacy to 10 mg/die oxazepam in the therapy of non-organic insomnia.

Adolescent↗
PubMed2006

Commercial valerian interactions with [3H]Flunitrazepam and [3H]MK-801 binding to rat synaptic membranes.

Valeriana officinalis extracts are used in folkloric medicine for their sedative, hypnotic and tranquilizer effects. Using [3H]flunitrazepam binding as an indicator, the interactions of commercial Valerian extracts with GABA(A) receptors were examined. There was considerable fluctuation among the different extracts, some mildly enhanced [3H]flunitrazepam binding, others had no effect and others had inhibitory effects, independent of standardization by valerenic acid. Central depression can also be accomplished by a reduction of excitatory transmission. Valerian extracts had modest inhibitory effects on [3H]MK-801 binding, an indicator of NMDA-Valerian interactions. Spectral analyses (UV region) did not show marked differences among the different extracts. The inhibitory effects of one of the extracts on [3H]flunitrazepam binding was somewhat stable, while on [3H]MK-801 binding the inhibitory effects were lost within months. These results suggest that particular care should be taken in analysing and interpreting results from commercial Valerian preparations.

Animals↗
PubMed1985

Effect of valerian on human sleep.

The effect of an aqueous extract of valerian root on sleep was studied in two groups of healthy, young subjects. One group (N = 10) slept at home, the other (N = 8) in the sleep laboratory. Sleep was evaluated on the basis of questionnaires, self-rating scales and night-time motor activity. In addition, polygraphic sleep recordings and spectral analysis of the sleep EEG was performed in the laboratory group. Under home conditions, both doses of valerian extract (450 and 900 mg) reduced perceived sleep latency and wake time after sleep onset. Night-time motor activity was enhanced in the middle third of the night and reduced in the last third. The data suggest a dose-dependent effect. In the sleep laboratory, where only the higher dose of valerian was tested, no significant differences from placebo were obtained. However, the direction of the changes in the subjective and objective measures of sleep latency and wake time after sleep onset, as well as in night-time motor activity, corresponded to that observed under home conditions. There was no evidence for a change in sleep stages and EEG spectra. The results indicate that the aqueous valerian extract exerts a mild hypnotic action.

Adult↗