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Brain Res Mol Brain Res. 2005 May 24; [Epub ahead of print] Related Articles, Links
Valerian extract and valerenic acid are partial agonists of the 5-HT(5a) receptor in vitro.
Dietz BM, Mahady GB, Pauli GF, Farnsworth NR.
Department of Pharmacy Practice, College of Pharmacy, University of Illinois, 833 S. Wood Street, Rm 122, MC 886, Chicago, IL 60612, USA; NIH Center for Botanical Dietary Supplements Research, University of Illinois at Chicago, College of Pharmacy, 833 S. Wood Street, Chicago, IL 60612, USA.
Insomnia is the most frequently encountered sleep complaint worldwide. While many prescription drugs are used to treat insomnia, extracts of valerian (Valeriana officinalis L., Valerianaceae) are also used for the treatment of insomnia and restlessness. To determine novel mechanisms of action, radioligand binding studies were performed with valerian extracts (100% methanol, 50% methanol, dichloromethane [DCM], and petroleum ether [PE]) at the melatonin, glutamate, and GABA(A) receptors, and 8 serotonin receptor subtypes. Both DCM and PE extracts had strong binding affinity to the 5-HT(5a) receptor, but only weak binding affinity to the 5-HT(2b) and the serotonin transporter. Subsequent binding studies focused on the 5-HT(5a) receptor due to the distribution of this receptor in the suprachiasmatic nucleus of the brain, which is implicated in the sleep-wake cycle. The PE extract inhibited [(3)H]lysergic acid diethylamide (LSD) binding to the human 5-HT(5a) receptor (86% at 50 mug/ml) and the DCM extract inhibited LSD binding by 51%. Generation of an IC(50) curve for the PE extract produced a biphasic curve, thus GTP shift experiments were also performed. In the absence of GTP, the competition curve was biphasic (two affinity sites) with an IC(50) of 15.7 ng/ml for the high-affinity state and 27.7 mug/ml for the low-affinity state. The addition of GTP (100 muM) resulted in a right-hand shift of the binding curve with an IC(50) of 11.4 mug/ml. Valerenic acid, the active constituent of both extracts, had an IC(50) of 17.2 muM. These results indicate that valerian and valerenic acid are new partial agonists of the 5-HT(5a) receptor.
Neurotox Res. 2004;6(2):131-40. Related Articles, Links
Neuroprotective properties of Valeriana officinalis extracts.
Malva JO, Santos S, Macedo T.
Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal. email@example.com
Valeriana officinalis have been used in traditional medicine for its sedative, hypnotic, and anticonvulsant effects. There are several reports in the literature supporting a GABAergic mechanism of action for valerian. The rationale of the present work is based on the concept that by decreasing neuronal network excitability valerian consumption may contribute to neuroprotection. The aim of our investigation was to evaluate the neuroprotective effects of V. officinalis against the toxicity induced by amyloid beta peptide 25-35 Abeta(25-35). Cultured rat hippocampal neurons were exposed to Abeta(25-35) (25 microM) for 24-48 h, after which morphological and biochemical properties were evaluated. The neuronal injury evoked by Abeta, which includes a decrease in cell reducing capacity and associated neuronal degeneration, was prevented by valerian extract. Analysis of intracellular free calcium (Ca(2+)i) indicated that the neuroprotective mechanisms may involve the inhibition of excess influx of Ca2+ following neuronal injury. Moreover, membrane peroxidation in rat hippocampal synaptosomes was evaluated, and our data indicate that valerian extract partially inhibited ascorbate/iron-induced peroxidation. In conclusion we show evidence that the signalling pathways involving Ca(2+)i and the redox state of the cells may play a central role in the neuroprotective properties of V. officinalis extract against Abeta toxicity. The novelty of the findings of the present work, indicating neuroprotective properties of valerian against Abeta toxicity may, at the long-term, contribute to introduction of a new relevant use of valerian alcoholic extract to prevent neuronal degeneration in aging or neurodegenerative disorders.
CNS Spectr. 2001 Oct;6(10):841-7. Related Articles, Links
The use of valerian in neuropsychiatry.
Krystal AD, Ressler I.
Department of Psychiatry and Behavioral Science, Duke University Medical Center, Durham, NC, USA.
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.
Phytother Res. 2004 Oct;18(10):831-6.
A double-blind, placebo-controlled investigation of the effects of two doses of a valerian preparation on the sleep, cognitive and psychomotor function of sleep-disturbed older adults.
Diaper A, Hindmarch I.
HPRU Medical Research Centre, University of Surrey, Guildford, Surrey, UK. firstname.lastname@example.org
One of the most popular herbal remedies for the alleviation of sleep problems is valerian. However, research into valerian is sparse, and studies differ greatly with respect to design, measures, and preparations used. This clinical study used standardized sleep EEG and psychometric tests to evaluate the clinical efficacy of a valerian preparation (Li 156). A placebo-controlled three way crossover clinical trial was completed using 16 (5 male and 11 female) sleep-disturbed participants (aged 50 to 64 years, mean age 55.9, SD 4.68). Participants slept overnight in a sleep laboratory, following a 21:00 hours dose of valerian 300 mg, valerian 600 mg, or placebo (double-blind). EEG sleep was recorded for each participant at 23:00 hours until 07:00 hours, when a psychometric evaluation was performed the morning after dose. Test periods were separated by six days washout period. Results showed no significant effect between valerian 300 mg, valerian 600 mg or placebo on any EEG parameter or psychometric measure. This suggests valerian at these doses is ineffective as an acute dose for sleep problems. However, valerian is widely used, and is traditionally sedative. Therefore, more research is required into therapeutic dose, types of valerian preparation, and the optimum period of use for therapeutic effect
Holist Nurs Pract. 2004 May-Jun;18(3):120-6. Related Articles, Links
Valerian use for sleep disturbances related to rheumatoid arthritis.
Taibi DM, Bourguignon C, Taylor AG.
Center for the Study of Complementary and Alternative Therapies, University of Virginia, School of Nursing, Charlottesville, VA 22908, USA. email@example.com
Complementary therapies are becoming increasingly popular, particularly for symptoms such as sleep disturbance. The herb valerian may be useful as a mild sleep aid in clinical populations, such as persons with rheumatoid arthritis. This article reviews valerian to inform healthcare providers of potential uses and safety considerations.
Integr Cancer Ther. 2004 Jun;3(2):128-48. Related Articles, Links
Safety and efficacy of herbal sedatives in cancer care.
Block KI, Gyllenhaal C, Mead MN.
Block Center for Integrative Cancer Care, Evanston, Illinois 60201, USA.
Insomnia and other sleep disturbances are common in cancer patients. Insomnia is a multifactorial health concern that currently affects at least 1 in 3 cancer patients, and yet most insomnia sufferers do not consult their physician regarding pharmaceutical options for relief. Use of hypnotic drugs (primarily benzodiazepines) is associated with increasing tolerance, dependence, and adverse effects on the central nervous system. While hypnotic drug use declined substantially in the past decade, the use of herbal sedatives appeared to increase. Mostly self-prescribed by lay people, herbal sedatives hold widespread appeal, presumably because of their lower cost and higher margin of safety when compared to pharmaceuticals. Studies of better-known herbal sedatives, notably valerian and kava, showed moderate evidence for both safety and efficacy for valerian while revealing disturbing toxicity concerns for kava. Milder sedatives or anxiolytics in need of clinical study include German chamomile, lavender, hops, lemon balm, and passionflower; St. John's wort may have anxiolytic effects with relevance to sleep. Herb-drug interactions are a possibility for some of these species, including St. John's wort. Although sufficient evidence exists to recommend some of these agents for short-term relief of mild insomnia, long-term trials and observational studies are needed to establish the safety of prolonged use as well as overall efficacy in the context of cancer treatment and management.