By Ted Waszkuc, NOW Quality Control Department
Valerian, Valeriana officinalis L. (Valerianacea) has a long history of use in temperate regions of Europe as a mild sedative due to its documented central nervous system (CNS) depressant activity.1 It has been used therapeutically since the Greek and Roman periods and currently is a top-ranking herb worldwide as a remedy for anxiety and insomnia.
Native to Europe and most often used by Western herbalists, V. officinalis is a hardy and adaptable perennial plant. It was transported to the New World by early settlers and now grows in much of the northern United States and southern Canada. The medicinally valued material consists of underground parts; i.e. roots and rhizomes. Nowadays, for medicinal use, it is largely cultivated in Northern and Central Europe.
Investigations of this plant have focused on finding and isolating the active constituents.2-6 During the last 30 years the identity of substances believed to be responsible for Valerian’s tranquilizing effect have frequently changed and still remains controversial.7 Two major groups of constituents can be distinguished, both terpenoid in nature: Iridoids and Sesquiterpenes.
Iridoids found in Valerian root consist of monoterpenic epoxy-triesters derivatives collectively known as a Valepotriates, (Valeriana epoxy-triesters). Different acid substituents, mainly Isovaleric acid and its derivatives, can be esterified to the hydroxyl groups present in Valepotriates. They were isolated from the plant and found to demonstrate sedative activity. Valepotriates are unstable and hydrolyze rapidly in a presence of moisture, or acidity (pH < 3) and even moderate heat (> 40°C); hence they have a short life in liquid preparations. Due to this fact, phytomedicines containing Valepotriates are usually formulated as solid dosage products like tablets or powder-filled capsules. The noticeably unpleasant smell associated with Valerian is due to the odor of Isovaleric acid formed upon hydrolysis of Isovaleric Valepotriate esters. Since liquid preparations of Valerian, such as alcoholic tinctures and teas, are still pharmacologically active, constituents other than iridoids must be responsible for their sedative effect.
Sesquiterpenic carboxylic acids, namely Valerenic, Acetoxyvalerenic and Hydroxyvalerenic acid, represent the other class of compounds2,3,6 thought to be responsible for Valerian preparations’ activity. Valerenic acid is a spasmolitic and muscle relaxant and inhibits the breakdown of g-Aminobutyric acid (GABA) at nerve endings.8 The presence of Valerenic acids (usually about 0.3%) distinguishes V. officinalis from other Valerinacea, which comprises about 200 known species. Only a few other than V. officinalis have medicinal uses, with Mexican valerian (Valeriana edulis) and Indian valerian (Valeriana wallichii) as the most common examples. Mexican and Indian plant material mainly contain valepotriates (about 7% w/w and up to 3% w/w, respectively). On the contrary, Valepotriates level in European Valerian ranges from 0.5% to 1.2%, with most commercial products averaging at 0.6%.9 None of the Valerenic acids could be detected in V. edulis or V. wallichii.
The synergistic effect of all the plant’s constituents is now believed to account for valerian’s pharmacological action. Due to considerable variation in Valerian preparations’ composition and content - as well as the instability of some of its constituents - standardization of Valerian products requires choosing stable, analytically reliable active or marker compounds characteristic of the plant material. Standardization of Valeriana officinalis preparations on Valerenic acids content is an illustrative example when the marker compounds utilized to confirm sample authenticity and potency may/or may not be active ingredients. Valerenic acids are stable, non-volatile substances, unique to Valeriana species, quantifiable by HPLC technique and commercially available as reference standards with a moderate cost. Although both Valepotriates and Valerenic acids are still considered to contribute to Valerian’s sedative action, it is widely acknowledged that standardization of Valerian-containing phytomedicines (Valeriana officinalis), using Valerenic acids as identity markers measured by HPLC technique, should be preferred.
To assure the quality of NOW Foods’ Valerian-containing products we developed the HPLC method based on the validated USP assay for Valerenic acid content. The method is modified to quantify all three Valerenic acids and is specific for V. officinalis products in both solid and liquid forms. It can also serve as a reliable check for all Valerian products’ authenticity. This is but one example of how NOW Foods uses science to assure that only top quality active ingredients are used in our products.
1 Houghton, P.J., Journal of Ethnopharmacology, 22 ,121-142 (1988)
2 Stoll, A., Seebeck, E., Liebigs Ann.Chem 603, 158-168(1957)
3 Buechi, G., Popper, T.L., Staufacher, D., J.Amer.Chem.Soc. 82,2962 (1960)
4 Thies, P.W., Tetrahedron, 24,313-347 (1967)
5 Hazelhoff, B.,Weert, B, Denee, R. and Malingre, Th.M., Pharmaceutisch Weekblad Scentific Edition, V1,140-148 (1979)
6 Bos, R., Hendriks, H., Bruins, A.P., Kloosterman, J., Simpa, G., Phytochemistry, 25, 133-135 (1986)
7 Bruneton, J., Pharmacognosy, Phytochemistry, Medicinal Plants, p.595 –600 (1999)
8 Riedel, Planta Medica, 46,219 (1982)
9 American Herbal Pharmacopea and Therapeutic Compendium, Valerian Root, April 1999