Valerenic acid

Yuan CS, Mehendale S, Xiao Y, Aung HH, Xie JT, Ang-Lee MK. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004 98 353-358. 

Vinyl phosphonates have been used in the construction of valerenic acid terpenoids 169 (Scheme 42).101 Both five-and six-membered rings can be formed via the vinyl phosphonate Alder-ene reaction which can be catalyzed by a variety of Lewis acids. The resulting structures 167 are suitable for Wittig-Horner reaction to give diene 168. Subsequent reactions access valerenic acid terpenoids 169. The chirality of the carbon bearing the phosphonate and ester is transferred, but is subsequently lost in the Wittig-Horner step. 

The sesquiterpenes present in valerian include isovaleric acid, valerenic acid, valerenal, valeranone, and valerenol. The alkaloids found in valerian include valeranine and actinidine. 

Riedel E, Hansel R, Ehrke G. (1982). [Inhibition of gamma-aminobutyric acid catabolism by valerenic acid derivatives]. Planta Med. 46(4) 219-20. 

Riedel, E., Hansel, R., and Ehrke, G. (1982) inhibition of GABA catabolism by valerenic acid derivatives. Planta Med 46 219-220. 

The commercial valerian products consist of, or are derived from, the rhizome, roots, and stolons of Valeriana officinalis L. The crude herb is dried and may be used as is or to prepare an extract that can be used to make an oral solution, tablet, capsule, or tea. Active constituents of valerian include acetoxyvalerenic acid, 1-acevaltrate, baldrinal, didrovaltrate, hydroxyvalerenic acid, kessane derivatives, valeranone, valerenal, valerenic acid, and valtrate (Figure 65.1). 

Note Valerian consists of the dried rhizome and roots of Valeriana officinalis Linne (Fam. Valerianaceae). It has been employed as an antianxiety agent and sleep aid for more than 1000 years. The drug contains from 0.3 to 0.7% of an unpleasant-smelling volatile oil containing bornyl acetate and the sesquiterpenoids, valerenic acid, and acetoxyvalerenolic acid. Also present is a mixture of lipophilic iridoid principles known as valepotriates. These bicyclic monoterpenoids are quite unstable and occur only in the fresh plant or in material dried at temperatures under 40°C. Although the specific active principals of valerian have not been determined, it is possible that a combination of the sesquiterpenoids and the valepotriates may be involved. The drug may be administered as a tea prepared from 2 to 3 g of the dried herb or equivalent amounts of a tincture or extract may be employed. 

Aqueous and hydroalcoholic extracts of valerian induce the release ur[ H]y-uminohutyric acid (GABA) from synap-tosomc preparations. Tlte extracts appear to have much the same effects as bcnxodiuzepines. except that valerian does not act on the Na VK -ATPase. Valerenic acid inhibits the GABA transamina.se. This effect would increase the inhibitory effc cl of GABA in the CNS. 

Key Words Valerenic acid valepotriates monoterpenes sesquiteipenes anxiolytic hypnotic. 

GABA. Dihydrovaltrate, hydroxyvalerenic acid, a hydroalcoholic extract containing 0.8% valerenic acid a lipid extract an aqueous extract of the hydroalcoholic extract, and another aqueous extract of V. officinalis (L.) were assessed for in vitro binding to rat GABA, benzodiazepine, and barbiturate receptors (18). The results indicated that an interaction of some component of the hydroalcoholic extract, the aqueous extract derived from the hydroalcoholic extract, and the other aqueous extract had affinity for the GABAa receptor. Because hydroxyvalerenic acid (a volatile oil sesquiterpene) and dihydrovaltrate (a valepotriate) did not show any notable activity, the investigators could not identify the specific constituents responsible for this activity. The lipophilic extract derived from the hydroalcoholic extract, as well as dihydrovaltrate, showed affinity for barbiturate receptors, and some affinity for peripheral benzodiazepine receptors. 

One study has evaluated the pharmacokinetics of valerian following administration to humans (32). Following administration of a single 600-mg dose of valerian, the pharmacokinetics of valerenic acid were measured. The Tmax occurred between 1 and 2 hours and the Cmax was between 0.9 and 2.3 ng/mL. Concentrations of valerenic acid were measurable for at least 5 hours following the dose. The elimination half-life was approx 1 hour. The authors suggest that based on the expected use of valerian (sedative effects), dosing 30 minutes to 2 hours prior to bedtime would be appropriate based on the previously mentioned pharmacokinetics. 

Hendriks H, Bos R, Woerdenbag HJ, Koster AS. Central nervous depressant activity of valerenic acid in the mouse. Planta Med 1985 51 28-31. 

Anderson GD, Elmer GW, Kan tor ED, Templeton IE, Vitiello MV. Pharmacokinetics of valerenic acid after administration of valerian in healthy subjects. Phytother Res 2005 19 801-803. 

Sample Number St. John s Wort % Hypericins Valerian % Valerenic Acids Echinacea purpurea % Total Phenols... 

Shohet et al. analyzed 31 commercial valerian preparations available in Australia, including tea, tablets, capsules and liquids, by HPLC for valepotriates, valerenic acid and valerenic acid derivatives. The concentrations of valerenic acid and its derivatives ranged from 0.01 to 6.32 pg g of the product powdered capsules on average contained the highest concentrations of valerenic acid and liquid preparations had the lowest concentrations. Torrado studied the in vitro release of valerenic and hydroxyvalerenic acids from valerian tablets. The valerenica acid and hydroxyvalerenic acid concentrations were measured by HPLC using a Cig Kromasil column (200 x 4.6 mm i.d., particle size 5 pm) and a mobile phase of methanol-aqueous 0.5% (v/v) orthophosphoric acid (75 25 v/v). The flow-rate was 1 mL mill. The uncoated tablets had the fastest release profile whereas the coated tablets showed very different release patterns, depending on the type of formulation. ... 

Shohet D, Wills RB, Stuart DL. Valepotriates and valerenic acids in commercial preparations of valerian available in Australia. Pharmazie 2001 56 860-863. 

Sedative properties have been documented for valerian and have been attributed to both the volatile oil and the valepotriate fraction. Screening of the volatile oil components for sedative activity concluded that valerenal and valerenic acid were the most active compounds. 

Valerenic acid inhibits the enzyme system responsible for the central catabolism of GABA. Increased concentrations of GABA give a decrease in CNS activity, which is involved in the sedative action of valerenic acid. 

Valepotriates, Valerenic Acid Derivatives Plant roots 40 0.78 150... 

Yourlife valerian is standardized to 0.8% valerenic acid. The recommended dose is two 100-mg soft gels at bedtime with a full glass of water. 

Twinlab TruHerbs timed release valerian is standardized to 0.8% valerenic acid. Each capsule contains 450 mg of valerian (300 mg of valerenic acid and 150 mg of valerian root). The capsules are designed to release the herb over 12 h. The recommended dose is one capsule daily. 

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