valerenic-acid and Sleep-Initiation-and-Maintenance-Disorders

Valeriana edulis ssp. procera, commonly known as "valeriana mexicana", is widely used in Mexican traditional medicine for the treatment of insomnia and anxiety. To evaluate the hypnotic effect and safety of 450 mg of Valeriana edulis standardized hydroalcoholic extract in patients with insomnia, a double-blind, cross-over, controlled study was carried out. Valeriana officinalis extract, at the same doses, was used as a positive control. In a sleep laboratory, polysomnographic (PSG) recordings were performed for analyzing the quantity and architecture of sleep as well as evaluating morning sleepiness, memory quotient, and side effects. The experimental procedures were conducted on four consecutive nights of 8 h each. Twenty patients were admitted. Based on the PSG results, V. edulis reduced the number of awaking episodes while both treatments increased the rapid eye movement (REM) sleep; this last parameter was better improved by V. officinalis extract. Other PSG data did not achieve outstanding statistical differences, but the clinical tendency with both treatments was to increase the sleep efficiency index. These Valeriana extracts produced beneficial effects on sleep architecture because they diminished the time of stages 1 and 2 in non-REM sleep while they increased delta sleep. Validated clinical tests showed that both species reduced notoriously the morning sleepiness, that was further improved by V. officinalis extract, and did not affect anterograde memory. In only three cases were slight side effects observed, one due to the experimental extract. Chemical analysis of the hydroalcoholic extract of V. edulis indicated that this extract contains 0.26 % of dihydroisovaltrate as the main valepotriate, and that it does not contain valerenic acid. In general, the results support the hypnotic effect and safety of acute treatment of Valeriana edulis and Valeriana officinalis on patients suffering insomnia.

Topics: Adult; Anxiety; Cross-Over Studies; Double-Blind Method; Female; Humans; Indenes; Male; Memory; Middle Aged; Phytotherapy; Plant Preparations; Polysomnography; Reference Standards; Rhizome; Sesquiterpenes; Sleep Initiation and Maintenance Disorders; Sleep, REM; Valerian

Insomnia is a commonly reported clinical problem with as many as 50% of older adults reporting difficulty in falling and/or remaining asleep. Valerian (Valeriana officinalis) is a commonly used herb that has been advocated for promoting sleep. Valerenic acid is used as a marker for quantitative analysis of valerian products with evidence of pharmacological activity relevant to the hypnotic effects of valerian. The objective of this study was to determine the pharmacokinetics of valerenic acid in a group of elderly women after receiving a single nightly valerian dose and after 2 weeks of valerian dosing. There was not a statistically significant difference in the average peak concentration (C(max)), time to maximum concentration (T(max)) area under the time curve (AUC), elimination half-life (T(1/2)) and oral clearance after a single dose compared with multiple dosing. There was considerable inter- and intra-subject variability in the pharmacokinetic parameters. C(max) and AUC deceased and T(1/2) increased with increased body weight. The variability between the capsules was extremely low: 2.2%, 1.4% and 1.4%, for hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid, respectively. In conclusion, large variability in the pharmacokinetics of valerenic acid may contribute to the inconsistencies in the effect of valerian as a sleep aid.

Topics: Aged; Aged, 80 and over; Area Under Curve; Body Weight; Female; Half-Life; Humans; Hypnotics and Sedatives; Indenes; Middle Aged; Oils, Volatile; Phytotherapy; Sesquiterpenes; Sleep Initiation and Maintenance Disorders; Valerian