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AmericanHerbal Pharmacopoeia

and herapeutic ompendium

alerian oot
Valeriana officinalis
Analytical, Quality Control,
and Therapeutic Monograph

April 1999
Editor: Roy Upton Herbalist
Associate Editor
Cathirose Petrone

Research Associates
Diana Swisher BA
Alicia Goldberg BA

Board of Directors
Executive Director
Roy Upton Herbalist

Michael McGuffin

Joseph Pizzorno ND


Authors Final Reviewers Silena Heron ND
American Association of
History, Commercial Sources Reinder Bos PhD Naturopathic Physicians
and Handling, Toxicology Rijksuniversiteit Groningen Sedona, AZ
University Center for Pharmacy
Roy Upton Herbalist Christopher Hobbs LAc Herbalist
Department of Pharmaceutical
American Herbal Pharmacopoeia™ Institute for Natural Products
Santa Cruz, CA Research
Groningen, The Netherlands
Bonny Doon, CA
Prof Dr Josef Hölzl
Botany Institut für Pharmazeutische David Hoffmann MNIMH
Alison Graff PhD Biologie California Institute for Integral
American Herbal Pharmacopoeia™ Der Philipps-Universität Studies
Santa Cruz, CA Marburg/Lahn San Francisco, CA
Marburg, Germany Prof Dr Johann Jurenitsch
Microscopy Institute for Pharmacognosy
Therapeutics University of Vienna
Elizabeth Williamson BSc PhD Vienna, Austria
MRPharmS FLS Pharmacokinetics and
Centre for Pharmacognosy Pharmacodynamics Glen Larkin MS
The School of Pharmacy Houghton, MI
Marilyn Barrett PhD
University of London Pharmacognosy Consulting Services Amanda McQuade Crawford
London, England Redwood City, CA MNIMH
Ojai Center for Phytotherapy
Constituents Ojai, CA
Amanda Bevill Herbalist Review Committee Dennis McKenna PhD
The Herbalist Mark Blumenthal Marine on St. Croix, MN
Seattle, WA American Botanical Council Prof Dr Beat Meier
Austin, TX Zeller AG Herbal Remedies
Analytical Methods Mary Bove ND MNIMH Romanshorn, Switzerland
Substantiating Laboratories Brattleboro Natural Health Clinic Lisa Meserole ND
Volatile Oil Assay Brattleboro, VT Seattle Healing Arts
Francis Brinker ND Seattle, WA
Forouz Ertl PhD
Botanicals International Southwest College of Thomas Miller PhD
Long Beach, CA Naturopathic Medicine Alpha Chemical and Biomedical
Tucson, AZ Laboratories
Thin Layer Chromatography Petaluma, CA
Gary Clapp PhD
Eike Reich PhD Hauser Laboratories Jennifer Montgomery-Salguero RPh
CAMAG Boulder, CO Severna Park, MD
Muttenz, Switzerland
Steven Dentali PhD James Mutch RPh
Marisol Martinez BS Dentali Associates Integrated Healing Arts
Botanicals International Troutdale, OR Los Altos, CA
Long Beach, CA
Staci Eisner Prof Dr Adolf Nahrstedt
High Performance Liquid Technical Director Editor Planta Medica
Chromatography ExtractsPlus Westfälische Wilhelms
Vista, CA Universität Münster
Mark Lange PhD Münster, Germany
Industrial Laboratories Trish Flaster MS
Denver, CO Botanical Liaisons Inc Andrew Pengelly BA DBM ND
Boulder, CO DHom
Wendy Wang PhD National Herbalists Association of
Frontier Cooperative Herbs Adriane Fugh-Berman MD
National Institutes of Health Australia
Norway, IA New South Wales, Australia
Rockville, MD
Steven Foster Specialist in Clarissa Smith Herbalist
Medicinal and Aromatic Plants Seattle, WA
Fayetteville, AK Andrew Weil MD
Constance Grauds RPh College of Medicine
Association for Natural Medicine University of Arizona
Pharmacists Tucson, AZ
San Rafael, CA Qun Yi Zheng PhD
Daniel Gagnon Herbalist Pure World Botanicals Inc
Herbs Etc South Hackensack, NJ
Santa Fe, NM

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cited valerian as being an aromatic stimulant and NC. including its use for rheumatism. epilepsy. Hobbs 1989). Respected American medical botanist William Woodville reported that various European authorities ascribed antispas- modic. Common Names United States: Valerian France: Valeriane Germany: Baldrian Italy: Amantilla United Kingdom: Valerian HISTORY The name valerian is said to be derived either from Valerius. AD 131-208) reported on its sedative effects (Pickering 1879). However. The name valerian was first used around the 9th and 10th centuries and was an entry in the domestic books of home remedies as early as the 11th century. The whole botanical contains not less than 0. Fifty years later. or from the Latin term valere. s. additional reports of its effectiveness in three cases of epilepsy were reported by Dominicus Panarolus. NC reported some unique indications. It was also listed in official compendia throughout the world. but subsequently was also reported to have relapsed. diaphoretic. John King. Valerian was included in many editions of the United States Dispensatory which reported on its effect on the nervous system and its ability to produce drowsiness and sleep (Wood and Bache 1849). acclaimed American Dispensatory. roots. an opinion reportedly supported by the Edinburgh Dispensary (Woodville 1810). and valerian subsequently became routinely used for the treatment of various nervous dis- orders (Benigni and others 1971. It has been used medicinally for at least 2000 years. Pleasant Garden.N O M E N C L AT U R E Botanical Nomenclature Valeriana officinalis L. including the British Pharmacopœia in 1867 (British Pharmacopœia 1867). s.l. John Milton Scudder in Specific Medications (Scudder 1903) cites valerian as having activity as a cerebral stimulant. a medieval vocabulary of the schools of Salernum (Flückiger and Hanbury 1879). Dioscorides (ca. Powdered material contains not less than 0. in his highly Photograph © 1999 Martin Wall Photography. Valerian was widely used by Eclectic physicians. meaning health or well-being (Grieve 1976). Location Gaia Herbs. and menopausal nervous anxiety (Ellingwood and Lloyd 1900). American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 1 . low grade fevers. who relat- ed a personal cure. John Finley Ellingwood in Systematic Treatise on Materia Medica and Therapeutics considered valerian to be a nervine and sedative for the treatment of hysteria.. anthelmintic. amantilla.l.. specifically when the condition is a result of “enfeebled cerebral circulation”. Botanical Family Valerianaceae Definition Valerian consists of the fragments or whole fresh or dried rhizomes. The names valerian. AD 40-80) wrote of several species of valerian (phu). It was first used as a treat- ment for epilepsy in the late 16th century reportedly by Fabius Columna. Woodville himself did not consider it to be as effectual as proclaimed by other writers. and stolons of Valeriana officinalis L. and emmenagogue actions to valerian and related its usefulness for hysteria. and as an aphrodisiac. who was reported to have first utilized its medicinal properties. Numerous reports by a wide variety of writers followed. as well as its use in hysteria (King 1866). and sedative useful in nervous irritability.5% (V/w) essential oil as determined on a dry weight basis. and fu were all used synonymously in the Alphita.3% (V/w) essential oil as determined on a dry weight basis. Brevard. diuretic. analgesic. and Galen (ca.

and the United States National Formulary until 1946. entire or dentate. V. has only a very faint characteristic. Cronquist 1981. s. The root is longitudinally wrinkled and approximately 100 mm long and 1-3 mm in diameter. Figure 2 Field of organically cultivated Valeriana officinalis Powder: Should be light brown or tan in color. Fruit: Achene crowned by persistent calyx. many pale pink to white. Figure 1a Valeriana officinalis cate at the base. hairy or glabrous. nonaddictive alternatives to conventional sleep medications. terminal or axillary. Various species of valerian continue to be included in the pharmacopoeiae of many nations such as Belgium. stamens 3. are brittle and break in short. All three of these sub- species. and central European supplies are tetraploid. which contain the majority of the essential oil. Distribution: Damp or dry meadows. slightly sac. lanceolate- oblong.l. Steinegger and Hänsel 1992. Inflorescence: Compound cyme. Brevard. repens Host. basal leaves petiolate. officinalis range in ploidy level from diploid to tetraploid or octaploid. 4. rhizomatous. However. lobes inconspicuous in flower. stigma tripartite. collina (Wallr. officinalis L. officinalis: ssp. opposite. as well as the other European species of valerian.the United States Pharmacopeia from 1820-1936 (Hobbs 1989). valeric acid- like aroma which becomes stronger as it ages. 5-lobed. The rhizome contains numerous thick. There are three subspecies of V. corolla funnel-form. The stolons are 20-50 mm long. obconical to cylin- drical. The rootlets. lobes 11- 21 lanceolate. is often dark brown.) Nyman. Gleason and Cronquist 1963. and a valerian monograph has been accepted by the United States Pharmacopeial Convention for inclusion in the National Formulary (Pharmacopeial Forum 1998). have been considered acceptable source material for medicinal preparations (Frohne and Jensen 1992. rare in the south. Germany. officinalis is usually octaploid. Populations of V. Italy. In longitudinal section. and ssp. Its widespread use as a sedative and antispasmodic in the United States continues. Taste: Mildly sweet and cam- phoraceous with a slightly bitter and spicy aftertaste (Reynolds 1993. NC Page 2 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . cultivated and naturalized in North America (Bailey and Bailey 1976. Stem: Solitary. It is commonly sliced in half for ease of cleaning. horny fractures and are whitish or yellowish internally (European Pharmacopoeia 1998). tube 4 mm.5-5 mm. almost cylindrical and almost the same color as the rhizome. Switzerland.. Aroma: When dried properly. Photograph courtesy of Bioforce of Switzerland light to dark brown rootlets which are located around a thin ligneous cord. V. lobes 1 mm. due to improper drying. ovary inferior. NC. Valerian preparations appear to be the most likely candidates to use as safe and effective. cauline leaves subsessile to clasping. Flower: Calyx 5-lobed. Location Gaia Herbs. filaments attached to Photograph © 1999 Roy Upton corolla tube alternate to corolla lobes. and the United Kingdom. oddly once pinnately lobed.) Celak. Pleasant Garden. Improperly dried or old material pos- sesses a strong and characteristic odor due to the enzymatic hydrolysis of esters of the valepotriates (isovaleric acid and hydroxyvaleric acid). becoming elongate and pappus-like in fruit. woods. It has a yellowish-brown to dark brown Figure 1b Valeriana officinalis exterior with a circular stem and leaf scars. sambucifolia (Mikan fil. Steinegger and Hänsel 1992). pale yellowish-grey with prominent nodes separated by longitudinally striated intern- odes. Hickman 1993). 15-150 cm. only 1 locule fertile. it Photograph © 1999 Martin Wall Photography. British V. Leaf: Basal and cauline. Most of Europe. Titz and others 1982. tri-loculate. the pith exhibits a central cavity transversed by septa. with an elongated or compressed base. Herbacious perennial. the whole rhizome is up to 50 mm long and up to 30 mm in diameter. uni-ovulate. When dried. ssp. strongly scented flowers. 1983). officinalis. hollow. Macroscopic Identification (Figures 3–8) Various chemotypes will have slightly different characteristics. I D E N T I F I C AT I O N Botanical Identification (Figures 1–2) Valeriana officinalis L. France. scrub.

Oregon Pharmacopoeia™ Pharmacopoeia™ Photograph Joanne Thompson © 1999 American Herbal Pharmacopoeia™ Figure 8 Dry Indian valerian Valeriana wallichi Sample courtesy of Nature Care Ayurvedic Products. Oregon Valeriana officinalis Photograph Joanne Thompson © 1999 American Herbal Photograph Joanne Thompson © 1999 American Herbal Sample courtesy of Pacific Botanicals. Grants Pass. Oregon Photograph Joanne Thompson © 1999 American Herbal Photograph Joanne Thompson © 1999 American Herbal Photograph Joanne Thompson © 1999 American Herbal Pharmacopoeia™ Pharmacopoeia™ Pharmacopoeia™ Figure 6 Dry organically cultivated Figure 7a Properly dried (note light tan Figure 7b Improperly dried (note dark Valeriana officinalis color) and cut organically cultivated brown color) and cut Valeriana officinalis Sample courtesy of Pacific Botanicals. Grants Pass. Grants Pass. Grants Pass. Guilderland. Grants Pass. Oregon Sample courtesy of Pacific Botanicals. Oregon Sample courtesy of Pacific Botanicals.Figure 3 Fresh organically cultivated Figure 4 Dry organically cultivated Figure 5 Fresh organically cultivated Valeriana officinalis var anthos Valeriana officinalis var anthos Valeriana officinalis Sample courtesy of Pacific Botanicals. NY Photograph Joanne Thompson © 1999 American Herbal Pharmacopoeia™ American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 3 .

g. Note: It is difficult to differentiate between pulverized V. d. up to 20 µm in diameter. Piliferous layer of the root showing some root hair scars (magnification 400X). Starch grains are numerous. j. officinalis. Epidermal tissue (objective 40X. Tegumentary tissue from rhizome showing brown contents (magnification 400X). b. CA Page 4 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . fragments of endodermis show sinuous walls. h. i. edulis (Woerdenbag and others 1997). wallichi. Vessels with reticulate thickening or bordered pits. and V. Epidermal cells (objective 40X. Sclereids from the stem base (mag- nification 800X). and numerous pits. V. l. Calcium oxalate absent.Microscopic Identification (Figures 9–10) Examine under a microscope using chloral hydrate solution. Sclereids from the rhizome are small with thick walls. Costa Mesa. magnification 400X). magnification 400X). thick-walled fiber (magnifica- tion 400X). c. magnification 400X). magnification 400X). magnification 400X). Piliferous layer shows cicatrices or occa- sionally attached unicellular root hairs and associated hypodermis of elongated cells. Lignified cells of tegumentary tissue from rhizome with brown granular contents. k. objective 40X. f. Parenchyma with starch granules (objective 40X. narrow branched lumen. e. Starch grains (objective 40X. Narrow. Root hair (magnification 400X). packed into parenchymatous cells of cortex and pith which are large elongat- ed cells with slightly thickened walls. Long Beach. Microscopic images courtesy of Botanicals International. magnification 400X). CA and Alkemists Pharmaceuticals. a b c d e f g h i j k l Figure 9 Microscopic images of Valeriana officinalis a. Parenchymatous cells of cortex or pith (transectional view. fibers occasional. Cortical parenchyma (longitudinal view. lignified with simple pits. Those from the base of the stem are larger with only slightly thickened walls. Endodermis of root with sinuous tangen- tial walls (magnification 400X). mainly 2-4 compound with cleft or radiate hilum.

harvest times. Analyses of material cultivated in the Netherlands report that the majority of constituents. the Netherlands. 7. coreana Briq. or those cultivated in phosphate-rich soil yields relatively high levels of essential oil (Bos and others 1998a). V. Figure 10 Microscopic characteristics of Valeriana officinalis 1.* = V. exaltata Mikan. Valerenic acid and valepotriates have been found to be present in fresh and dry samples of V. Fibers from stem base. American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 5 . V. Eastern Europe. V. Piliferous layer showing cicatrices and attached root hair. North America. A limited number of assays of material cultivated in the Pacific Northwest show varying levels of essential oil ranging from 0.9% to 1. Germany.. including the essential oil and valerenic acid. capitata Pall ex Link. Gray. A large number of liquid extracts are prepared from domestically cultivated material. growing conditions.9%) followed by material harvested in September (0. Sclereids from base of stem. Holland.5% essential oil.5% valerenic acid (Bos 1997). V. V. edulis Nutt. wallichi DC. syn. V. edulis Nutt.4%). reportedly are lacking in valerenic acid and its derivatives (Bos 1997). edulis Nutt. V. ex Torr.7%) and then in January (0.3%. and ≥ 0.7% to 0. Sclereids from rhizome. Tegumentary tissue showing brown contents. Förster and others 1984). & A. * V. and Russia (Evans 1996. ex Kom. jatamansi Jones* (Leung and Foster 1996. scouleri Rydb. Essential oil content also varies with genotypes. Older literature reports that valerian should be harvested in the fall.6%). Valerenic acid and its deriv- atives were found to be highest in February and March (0. The next highest level of essential oil was reported for material harvested in March (0. It has been reported that valerian harvested in higher elevations. Steinegger and Hänsel 1992). ≥ 30% extractable matter. ex Torr. grown in dryer regions. edulis Nutt. 3. diocia L.2% to 2. hardwickii Wall. Smirn. between August and September. The majority of standardized extract products and crude cut and sifted material on the domestic market are prepared from European supplies. Parenchyma. was high- est in roots harvested in the first year of growth with essential oil being highest in September and November (1. V. stubendorfi Kreyer ex Kom. amurensis P. V. sitchensis Bong and V. 6. and method of analysis.. Collection The majority of valerian in trade comes from cultivated material. dry- ing techniques. 4. & Gray ssp. The composition of the essential oil varies greatly among differ- ent populations of the same subspecies (Corsi and others 1984) and even between the same population of plants from year to year (Hazelhoff and others 1979). wallichi DC. sitchensis Bong (Anonymous 1996. The most frequently used North American species include V. Harvest times will vary geographically. preferably in the second year of growth (Violon and others 1983. 8. Youngken 1930).5% to 0. age of root. Japan. officinalis are reported to be traded as medici- nal valerian. ari- zonica Gray. procera (Kunth). France. These include V.. sitchensis Bong exhibits a strong pungency when fresh. 2. Steinegger and Hänsel 1992).4% to 1. COMMERCIAL SOURCES & HANDLING Valerian is cultivated in Britain. and V. and V. Many species other than V. and V. Starch grains. Belgium. 5.. Detailed chemical analyses of most American species are lacking. Other species reported to be used locally include V..0% to 1. Fragment of vessels.1%). High quality material is reported to contain from 1.k.3% to 0.

it can evaporate with excessive exposure to air. is formed when the herb is stored at too high humidity (Woerdenbag and others 1997). Because of the sensitivity of volatile oils to heat. In powdered root. Improper storage conditions can cause significant deterioration of the material. The following guidelines are provided in the literature.05 kg/sec/m2 (Elbanowska and others 1975). Cutting off the flowering tops before the plant has set seed causes the rhizome to develop more fully. This produces the characteristic valerianic aroma (Samuelsson 1992). Adulterants Other species of valerian. Because of this. air. and freeze-drying are also reported to be appropriate drying techniques (Benigni and others 1971. Preparations A variety of valerian root preparations are in commerce with various manufacturers preparing their products according to their own specifications utilizing fresh and/or dried material. Page 6 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . Excess washing of the roots can result in a significant reduction of extractive matter (Bos 1997). Lutowski and Turowska 1973). Alternatively. Careless or prolonged drying produces a darker color in the roots and results in the hydrolysis of the isovalerianic esters and the liberation of isovaleric and hydroxy- isovaleric acid. Handling The essential oil is located in the hypodermis of the rhizome in large thin-walled cells. No differences in content of valerenic acid and its derivatives are observed between these two methods (Bos 1997). Valepotriates are sensitive to humidity. Hydroxyvalerenic acid. and acid mediums (pH < 3) and are generally not detected in commercial products after 60 days (Houghton 1988. From a commercial standpoint. Drying For maximum preservation of the essential oils. there is a 50% decrease in essential oil content. the essential oil content can decrease by 50% within 6 months. Wichtl and Bisset cite that an unidentified Apiaceae species may be found in valerian trade (Wichtl and Bisset 1994). or by utilizing a cryo- genic grinder. shade drying at approxi- mately 45 °C. a decomposition product of acetoxyvalerenic acid. Cultivation Sowing seeds has been reported to be preferred over planting of seedlings. low temperature vacuum-drying. it is necessary to mini- mize the amount of time generated in the grinding or powdering process by doing small lots at a time. Wagner reports that harvest should take place in the morning during relatively cool weather (Wagner and others 1972). When dried at 50 °C as compared with drying at 20 °C. and moisture. temperatures above 40 °C. with frequent interruptions in run times. Bos 1997). Properly dried valerian will produce this same aroma over time. Adulteration of valerian in the American market is not common. Best results were achieved by flat field planting at row spacings of 50 cm and a seed rate of 3 kg/ha (Mheen 1996). it is more cost effective to harvest the roots in the same year the plants are sown than in the second year (Bos and others 1998a). a general recom- mendation for roots rich in essential oils. Although the essential oil is relatively stable. Storage Store in closed containers protected from light. The essential oil can degrade quickly in powdered material. care must be taken not to damage these cells during handling. dry- ing at room temperature (20 °C) for approximately 10 days. valerian should be dried at 40 °C with a flow rate of 0.

officinalis were found to contain valerenic acid and its derivatives and very low levels or no valepotriates (Bos 1997). In a limited number of analyses. and valerenic acid skeletons. teas prepared from V. GABA. Note: Valerenic acid derivatives begin to be extracted at alcohol concentrations above 30% and are relatively constant above 50%.and sesquiterpene hydrocarbons with the main constituents being bornyl acetate.Valerian Infusion Hot Infusion: 2-3 g of valerian steeped in 225 mL of boiled water for 10-15 minutes in covered vessel (Bradley 1992). prepared either by maceration or percolation at a concentration of 1 part herb to 5 parts water-alcohol menstruum (70% ethanol V/V).1% to 0. and various minerals. powder or pulverized mass with intense characteristic aroma. and alkaloids. Characteristics: Dark brown liquid with a strong characteristic valerian smell and taste. officinalis and its subspecies (Hänsel and Schulz 1982). valerianol. valeranone. officinalis contain several compounds with demonstrable pharmaco- logical activity. These include the essential oil and its sesquiterpenoids (valerenic acid). Cold Infusion: 2-3 g of valerian soaked in 225 mL of cold water for 6-8 hours (Osol and others 1947).25% essential oil (Hendriks and others 1981). glutamine. choline. Loss of Moisture on Drying: At most 5%. The relationship of the drug to the extract is between 4:1 and 7:1. Valerian Tincture Valerian tinctures are official in the Dutch. Valerian Fluid Extract Prepared either by maceration or percolation at a concentration of 1 part herb to 1 part water-alcohol menstruum (70% ethanol V/V) (Bos 1997). β-sitosterol. Storage: Store in tightly closed containers protected from light.00 g tincture as described in the mono- graph for tinctures. Valerian Root Dried Extract According to the German Pharmacopoeia (Deutsches Arzneibuch 10 1993) Prepared from the chopped roots of valerian and 70% ethanol (V/V) as described in the valerian extract monograph. Characteristics: Brown. amino acids (arginine. Characteristics: Dark brown liq- uid with a strong characteristic valerian smell and taste.5% essential oil based on dry weight. The sesquiterpenes have three types of structures based on kessane. Essential Oil (0. However. German. and valere- nal. Valepotriates are only extractable at alcohol concentrations above 70%. and Swiss pharmacopoeiae. chlorogenic acid. depending on the chemovar.6%) The essential oil content and composition of valerian varies significantly. tyrosine). caffeic acid. Very few studies have been conducted on fresh material with the most recent published report finding approximately 0. The essential oil contains mono. Storage: Store in tightly closed containers protected from light. hygroscopic. valeranone. valerosidatum. cryptofauronol. Valerian also possesses small amounts of phenolic acids and flavonoids. Storage: Protect from moisture and light. species other than those considered as part of the aggregate have also been American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 7 . Valerenic acid and its derivatives (acetoxyvalerenic acid and hydroxyvalerenic acid) have been reported to be characteristic of V. epoxy iridoid esters (valepotriates) and their decomposition products such as baldrinal and homobaldrinal. CONSTITUENTS The roots of V. fatty acids.06% essential oil. The German pharmacopoeia requires the finished tincture to yield a minimum of 3% (w/w) dry residue as determined on 3. Most phar- macopoeial standards require that valerian contain a minimum of 0. The Swiss pharmacopoeia requires the finished tincture to yield 0.

01% in fresh roots) (Drobot’ko and others 1958. valeranone (ca. and isovaleroxyhydroxydidrovaltrate position products (IVHD valtrate) (Samuelsson 1992. Numerous acid residues are found. and Valepotriate Degradation Products R valepotriates. Stahl and Schild 1971).1% alkaloids. Collect the filtrate and washings in a test tube and blow dry with nitrogen for the minimum time necessary to remove the solvent. officinalis contains at least 0. l-hydroxypinoresinol. Spot Test The 1998 edition of the European Pharmacopoeia provides the following spot test for authenticating Valeriana spp. and filter. Other secondary compounds include isoborneol. actinidine (0.002% in R R2 R3 R1 R2 R3 IV IV Ac Valtrate IV Ac IV Didrovaltrate fresh roots).2% (w/w) (Houghton 1988). AiV IV Ac Acevaltrate Franck and others 1970. trihydric alcohol. and esters (Bos 1997). β-caryopyl- lene. carveyl acetate (ca.8% valepotriates (Samuelsson 1992). Other primary compounds include valerianol. and dihydrocarveyl acetate (1% R1 R2 R to 2%) (Hazelhoff and others 1979. Dissolve the residue in 0. oxides. This alcohol has the struc- ture of an iridoid cyclopenta-(c)-pyran with an attached epoxide ring. Rinse the filter cake (solids) with 2 mL of methylene chloride and add the rinse to the filtrate. Because concern has been raised about the cytotoxicity of valepotriates. isobornyl isovalerate. 0. this test can be used to insure Figure 13 Valerian alkaloids the absence of valepotriates from powdered valerian products. edulis Nutt.03%) (Johnson and Waller 1971. The following methods have been adopted. Alkaloids Valepotriate The dried root contains 0. α-pinene (6.5% in V. let stand for 5 minutes. and pinoresinol-β-D-gluco- side (Bodesheim and Hölzl 1995). Torssell and Wahlberg 1967).005% to 40%). Shake well. chatinine (0. monocyclic. officinalis ssp. Valepotriates degrade rapidly.6% valepotriates (Steinegger and Hänsel 1992).5%).1 mL of the R methanol. shake several times. Page 8 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . This test is specific for valepotriates which occur in sev- eral species of valerian and is therefore not specific for V. V. especially in acidic solutions. β-pinene (ca. isovaleramide. Figure 11 Primary components of valerian More than 150 compounds have been reported in the essential oil. valeranone. phenols.76%). isobornyl acetate. the essential oil and valerenic acid are common. officinalis (Morazzoni and Bombardelli 1995). isoeugenyl-isovalerate. camphene (ca.2 g of freshly powdered root. ketones.4% to 0. Ac Baldrinal Vatroxal ly used as marker compounds for qualitative and quantitative analysis of valerian root IV Homobaldrinal and valerian products. pyrryl-α-methylketone (Balandrin and others 1996). officinalis. ter- pinolene. pinoresinol. aldehydes. borneol. didrovaltrate. Figure 12 Valepotriates and their decom- der consisting of acevaltrate. up to 8% in South American V. valerine. and as high as 14. valerenic acid. Valepotriate concentrations range from as little as 0. and bicyclic hydrocarbons as well as oxygen-containing deriva- tives such as alcohols. In the United States. including essential oil acyclic. or valere- nal. Violon and others 1984). including valerianine (0. Add 3 mL of a mixture of equal volumes of chilled acetic acid and hydrochloric acid to 0.found to contain valerenic acid and its derivatives (Bos 1997). thalictroides Graebn. 5%). Valtrate makes up approximately 80% to 90% of total valepotriates with the remain. (Marekov and others 1983). Add 5 mL of methylene chloride to 0. limonene (1% to 2%). Most European supplies contain an average of 0. When carefully dried.05% to 0. Bornyl acetate and isovalerate have been reported to be the primary components of the essential oil of V. dipyridylmethylketone. A N A LYT I C A L Analysis of valerian has primarily focused on the essential oil. 16%).2 mL of methanol. If valepotriates are present.5% to 2% in European V. cryptofauronol. the solution will turn a blue color CH2OCH Valerianine CH3 Actinidine within 15 minutes (European Pharmacopoeia 1998). Long 1987. V. officinalis sel- dom contains more than 1. 6. H COOH Valerenic acid Ac Bornyl acetate OH COOH Hydroxyvalerenic acid IV Bornyl isovalerate OAc COOHR1 Acetoxyvalerenic acid Epoxy Iridoid Esters (Valepotriates) H CHO Valerenal Valepotriates are triesters of a terpenoid. officinalis species (Hänsel and Schulz 1982).

The anisaldehyde-sulfuric acid reagent is colorless and should be stored in a refrigerator. NJ. however. Allow the mixture to stand for 5 minutes and then filter. 1997). this method has been adopted (see Ertl Journal AOAC Int 80(4): 1-6. Following application of the HCl-acetic acid reagent. dry in stream of cold air. the method of the European Pharmacopoeia (1998 supplement) and the method proposed by the United States Pharmacopeial Convention (USP) (Pharmacopeial Forum 1998) were compared. To this solution add 0.2 g of freshly powdered valerian in a test tube with 5 mL dichloromethane for 1 minute. place on plate heater (or in oven) at 120 ˚C for 2 minutes (or until color of standard has developed). valerenic acid appears as a strong dark blue band. Mobile Phase: Hexane:ethyl acetate:glacial acetic acid (65:35:0. MD) in 0. HPTLC) For thin layer chromatography analysis. Chromatographic Conditions Stationary Phase: HPTLC plates 10 x 10 cm silica gel 60 with fluorescence indicator (EM Science.2 mL of dichloromethane and transfer the solution into a small sample vial. this band appears as a very faint violet color in visible light and as a weak fluorescent band under UV 366 nm. Improvements were made to the sample preparation. Detection: a) UV 254 nm. the reagent must be discarded. Sample Application: 3 µl volumes of both sample solution and standard are applied each as a 10 mm band. officinalis. b) Spray plate with the HCl-acetic acid reagent. Somerville.48. and the United States Pharmacopeia. Space bands 6 mm apart. heat to 110 ˚C for 5 minutes. the procedures provided by AOAC have been detailed in such a manner as to minimize variables that can lead to dif- ferences in volatile oil yields and maximize reproducibility (Ertl 1997). Inspect plate in visible light and under UV 366 nm. Machery & Nagel. Thin Layer Chromatography (TLC. Prepare anisaldehyde-sulfuric acid reagent by slowly adding 9 mL of 98% H2SO4 to an ice cooled mixture of 85 mL of methanol and 10 mL of glacial acetic acid. Sample Preparation Shake 0. Each of these is similar. c) Spray the plate with the HCl-acetic acid reagent. Rockville. Wash the fil- ter with 2 mL of dichloromethane. Reagent Preparation Prepare HCl-acetic acid reagent (1:4) carefully mixing 20 mL of glacial acetic acid with 80 mL of concentrated hydrochloric acid. Assay for Volatile Oil There are three primary methods applicable for assaying volatile oil content of valer- ian root: AOAC International. Whatman. a primary marker compound of V. dry in stream of cold air.5). Rf Values: Valerenic acid = 0. United States Pharmacopeial Convention. Dissolve the residue in 0. The method of the European Pharmacopoeia method was preferred for analysis of valerenic acid. Standard Preparation Dissolve 1 mg of valerenic acid (available from Indofine Chemical Company. If a color develops. European Pharmacopoeia.5 mL of anisaldehyde and mix well. Following subsequent application of the anisaldehyde-sulfuric acid reagent.5 mL of dichloromethane. or equivalent). American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 9 . Because the determination of volatile oil is the primary qualitative and quantitative marker for effective valerian products. Evaporate the combined filtrate and washing to dryness on a water bath. Application position should be 8 mm from the lower edge of the plate.

Lane 2: V. acid reagent in visible light Lane 2: V. Lane 4: V. Lane 6: V. Lane 5: Valerenic acid. Lane 4: V. Lane 2: V. sitchensis. Lane 5: Valerenic acid. officinalis. Lane 6: V. wallichi (Indian valerian). Lane 1: V. Figure 16 HPTLC plate viewed after application of the HCl-acetic Figure 17 HPTLC plate viewed after exposure to both the HCl-acetic acid reagent viewed under 366 nm UV reagent and the anisaldehyde reagent Lane 1: V. radix (official standard from Swiss pharmacopoeia). officinalis (commercial material from Holland). Lane 3: V. Lane 5: Valerenic acid. sitchensis. radix (official standard from Swiss pharmacopoeia). sitchensis. Lane 3: V. Lane 5: Valerenic acid. Lane 7: V. Lane 2: V. Lane 4: V. Page 10 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . Lane 6: V. Lane 4: V. Lane 1: V. Lane 3: V. Lane 7: V. Lane 3: V. Lane 7: V. officinalis (commercial material from Holland). wallichi (Indian valerian). wallichi (Indian valerian). radix (official standard from Swiss pharmacopoeia). officinalis (organically cultivated). radix (official standard from Swiss pharmacopoeia). officinalis.Figure 14 HPTLC plate viewed under 254 nm UV Figure 15 HPTLC plate viewed after application of the HCl-acetic Lane 1: V. officinalis (commercial material from Holland). officinalis (organically cultivated). officinalis. officinalis. Lane 7: V. sitchensis. officinalis (organically cultivated). Lane 6: V. officinalis (commercial material from Holland). officinalis (organically cultivated). wallichi (Indian valerian).

56. Additionally. V.25.8. Another light blue band appears at Rf 0.85. Dilute to volume with methanol:water (80:20) and sonicate for 30 minutes. It provides good separation band at Rf 0. valerenic acid is seen as a very faint violet band at Rf 0.48.37 and 0. In Figure 14. Rf 0. wallichi is blue. band at Rf 0. Standards for acetoxyvalerenic acid and hydroxy valerenic acid are available and are relatively expensive. purity of the standard. and hydroxyvalerenic acid.4. sitchensis with the exception that the in the National Formulary (Pharmacopeial Forum 1998).48 between two broad Calculation of total valerenic acid values (the sum of valerenic acid. Valerenic acid is available and is relatively inexpensive. valerenal.5 and bands at the higher Rf are also missing. and 0. weigh 2 g of finely powdered root material and transfer to a 100 mL volumetric flask. Characterization of various Valeriana spp officinalis samples. valerenic acid is seen as a strong single band at Rf 0.85 and a blue fluorescence ment of various species of Valeriana. In the V. In Europe. The most intense band of V. In the V.53. officinalis sitchensis is at Rf 0. Dilute to volume with methanol:water (80:20) and sonicate for 15 min- utes. The band at the same Rf in for Valerenic Acid V. a blue and a pink band with two broad red bands directly above are seen in provided may be useful in quality control assess- the V. valerenic acid is seen as a strong dark blue band. The extinction coefficients of each compound are not the same.38 and 0. There are a blue and a brown band at Rf 0. Filter a portion through a 0. Standards for valerenal are not available but it is considered to have the same extinction coefficient as valerenic acid.18. weigh 100 mg of extract into a 10 mL volu- metric flask. and in some analytical laboratories in the United States.37. V. Depending on the extra band at Rf 0.48. wallichi is characterized by samples test show prominent dark blue bands of valerenic acid at Rf 0. the Dutch sample shows an In Figure 17. total sitchensis is characterized by two very strong valerenic acid content is calculated as the sum of these compounds.62. For analysis of powdered extracts. the band at Rf 0.85. No are present at an approximate Rf of 0. These differences in calculating band is present at Rf 0. acetoxyvalerenic acid. however. for each compound are the same. officinalis samples. Information about differenti- above. Sample Preparation For analysis of crude valerian root. the information same Rf. wallichi give significantly differ- ent chromatograms. Two or three violet bands are seen between Rf 0.48 and one or two dominating bands at Rf 0. 0. In the USP pro.37 and an intense High Performance Liquid Chromatography (HPLC) violet band at Rf 0. sitchensis is a brown band at Rf For quantitative analysis of valerenic acid.37 is more intense and of brown color. officinalis samples tested were iden- In Figure 15.53. a modification of the method of Hänsel 0.5. there is an extra reddish- brown band when viewed under 366 nm UV. acid.25 a) Under 254 nm UV. two more bands may appear at a lower Rf. three bands of decreasing intensity are seen above this band. At the with known compounds. This same method formed the No bands appear at Rf 0. For a more accurate determination of total valerenic acids. and the aldehyde In the Dutch sample. and Schulz was adopted (Hänsel and Schulz 1982). attempt has been made to correlate the bands In Figure 16. wallichi show laboratories calculate total valerenic acids using each reference standard while others a pattern similar to that of V. wallichi shows a valerenic acid content cause confusion and incongruities in the marketplace. acetoxyvalerenic brown bands.48. officinalis samples. sharp violet band at Rf 0. respectively. some analytical band at Rf 0. valerenic acid is seen as a weak fluorescent band at Rf 0. Two blue bands are seen below the valerenic acid band.55 and 0. V. All of the V.45 µm filter into an HPLC vial or centrifuge to obtain a clear test solution. The most intense band of V. the Dutch sample has an extra olive green band at Rf 0. American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 11 . An olive green and two gray bands ating between the species is provided below. lab- oratories are encouraged to determine the extinction coefficients of the three prima- ry compounds. There is also a blue band at Rf 0. and valerenal) is more representative of effective valerian c) The Dutch sample shows an extra olive green products than determination of valerenic acid alone. A by TLC (see Figures 14-17) sharp band is seen at Rf 0.53. An additional red posal.37. officinalis. wallichi is basis for the method proposed by the Pharmacopeial Convention (USP) for inclusion similar to V. Filter a portion through a 0. only valerenic acid content is determined.45 µm filter into an HPLC vial or centrifuge to obtain a clear test solution. The V.37. calculating total valerenic acids in this manner provides a more accurate determination of total valerenic acid values than the calculation of valerenic acid alone. V. b) Under visible light. sitchensis and V. sitchensis and V. and the two dark blue bands at Rf 0. and the bands at the high- er Rf are missing.8. white bands at Rf 0. the intensity of the bands is significantly different calculate total valerenic acids based on the assumption that the extinction coefficients in all three species.25 is olive green with a light violet band directly sitchensis and V. However. hydroxyvalerenic acid. However. V. tical with the exception of the Dutch sample. V. of valerenic acid.25.

Stability and Storage of Preparations The standard and sample are stable when stored in amber vials and are refrigerated. Somerville. Figure 18 Typical HPLC chromatogram of Valeriana officinalis Chromatogram courtesy of Hauser Laboratories. Injection Volume: 20 µL. NJ. Mobile Phase: Methanol:0. Boulder.6 x 250 mm (Alltech Hypersil). Rockville. 100V (C/W)(ru/rs) V is the volume in mL of the sample preparation. respectively. valerenic acid. Calculation Calculate the percentage of valerenic acid alone or total valerenic acids using the following formula. acetoxyvalerenic acid. MD) into a 100 mL volumetric flask. Run Time: 15 minutes. W is the weight in mg of valerian used to prepare the sample solution. Detection: 225 nm. Standard Preparation Accurately weigh 5 mg of valerenic acid standard (Indofine Chemical Company. Dilute to volume with methanol:water (80:20) and sonicate for 15 minutes. United States Pharmacopeial Convention. Chromatographic Conditions Column: C-18. ru and rs are the peak responses obtained from the sample solution and the standard solution. valerenal. Flow Rate: 1.5 mL/minute. CO Page 12 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . Elution Order: Hydroxyvalerenic acid. 4. C is the concentration in mg per mL of the standard solution. 5 µm.5% phosphoric acid (80:20).

Also. Small amounts of valepotriates and their decomposition products were reported to be found in the blood. these are similarly not present in commercial products. Negative for Salmonella species. Loss of Moisture on Drying: Not more than 12% determined on 10. Acid Insoluble Ash: Not more than 5% determined on 1 g herb (European Pharmacopoeia 1998). Allow to stand for 2 hours. Individual components have displayed activity. and unchanged valepotriates were reported in the stomach contents 15 hours after admin- istration. The greatest quantity of 14C- labeled valepotriates were found in the stomach lining and in the intestines. work by Gstirmer and Kind published in 1951 indicated that the essential oil account- ed for only one-third of the sedative activity of the extract (Gstirmer and Kind 1951). filter. Qualitative Standards Foreign Organic Matter: Not more than 5% stem bases. kidneys. However. shaking frequently. American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 13 . this activity could not be accounted for by valepotriates. The residue should weigh not less than 0. THERAPEUTICS Pharmacokinetics The only pharmacokinetic data available for valerian are regarding the valepotriates.1 g (European Pharmacopoeia 1998). officinalis containing low amounts of valepotriates showed a greater effect on hexobarbital-induced sleeping time than Chinese and Nepalese samples containing high amounts of valepotriates (Hikino and others 1980). and Staphylococcus aureus Microbial Contamination: (Pharmacopeial Forum 1998). Extractable Matter: Not less than 20%. Eickstedt and Rahman reported that valepotriate esters isolated from valer- ian demonstrated sedative activity in mice (Eickstedt and Rahman 1969). not more than 2% other foreign matter (European Pharmacopoeia 1998). Although metabolic by-products of valepotriates are considered to be more active than the valepotriates themselves. Escherichia coli. However. In addition. hav- ing an efficiency of 0. However. heart. evapo- rate filtrate to dryness on a water bath. and brain (Steinegger and Hänsel 1992). Another study with radioactive didrovaltrate administered to mice orally. intravenously.19% of the administered dose. lungs.0 g powdered herb (#355) dried at 100 °C to 105 °C for 2 hours (European Pharmacopoeia 1998). and dry the residue at 100 °C to 105 °C. valepotriates are not water soluble and were excluded as the active hypnotic in an aqueous extract which was found to be an effective sleep aid in clinical trials (Leathwood and Chauffard 1985). Japanese samples of V. but no single constituent has been shown to account for valerian’s total action.00 grams of powder (#250) with a mixture of 12 g ethanol (96%) and 8 g of water. the researchers found the bulk of the radioactivity in polymeric degradation products and confirmed a fast degradation or metabolic decomposition with in vitro studies using plasma and liver homogenates (Wagner and Jurcic 1980). Pharmacodynamics Research into the pharmacological activity of valerian has almost exclusively focused on its sedative and spasmolytic properties. and intraduodenally also reported poor absorption in the unchanged form. Total Ash: Not more than 12% determined on 1 g herb (European Pharmacopoeia 1998). Early in the 20th century. liver. it was believed that the essential oil was the com- ponent responsible for the sedative effect of valerian (Houghton 1988). Valepotriates administered orally to mice are reported to be poorly absorbed. Mix 2. The clinical relevance of this is largely inconsequential as valepotriates rapidly degrade in commercial products. an in vivo study measuring cerebral glucose turnover in rats found that although a dichloromethane extract demonstrat- ed depressant activity. In 1969.

05) and an increase in sleep quality (P < 0.01%). Sleep onset was determined by reduction in body movement as measured by wrist-worn activity monitors.05 mg valerenic acid and ace- toxyvalerenic acid. the dose recommended in the Swiss pharma- copoeia.05) as compared to placebo. using the same 450 mg valerian extract in a double- blind crossover study. and rapid fatigue due to the impaired sleep were evaluated in a placebo-controlled study. and EEG was reported (Balderer and Borbély 1985). Reduction of Page 14 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . was a double-blind clinical trial wherein 128 subjects received one of three samples: either an aqueous extract of valerian. both children (average age of 10) and adults (average age of 48). difficulty sleeping through the night. patients experiencing functional sleep disturbances and anxiety reported subjective improvement after treatment with the valerian preparation Baldrian-Dispert® (corresponding to Valdispert®) for 10 days.5 minutes (P < 0. despite a positive placebo effect (Donath and others 1996). Effect on Sleep Human Clinical Studies At least four clinical studies have been conducted on the effects on sleep using the same aqueous extract of V. through questionnaires. valeranone. reported a reduction in sleep latency (P < 0. Another research group. In the more recent of the two studies. Patients were given either placebo or 6 tablets daily of Valdispert®. These sub- jects were all healthy and good sleepers. polygraph. a product con- taining 45 mg dry valerian extract standardized to 0. or the essential oil of V.02) were observed after 14 days of treatment. In a subsequent double-blind. This preparation was made with deionized water heated to 60 °C and subsequently freeze-dried and reportedly contained only trace amounts of valepotriates (0. a commercial preparation containing extracts of valerian and hops strobiles (ratio of 2:1). Both valerian preparations con- tained 400 mg of valerian extract. The medication was well tolerated (Kamm- Kohl and others 1984). People who considered themselves poor or irregular sleepers obtained the most benefit.8 ± 2. In another study. including difficulty falling asleep. Valerian extract did not influence total sleep time or normal levels of movement during the night. who were good sleepers.2 minutes to 9. The authors con- cluded that valerian was at least as effective as small doses of barbiturates or benzodi- azepines (Leathwood and others 1982. or a placebo of brown sugar. Each tablet contained 45 mg of dry valerian extract. Significant improvements in the ability to fall asleep and to sleep through the night (P < 0.0 ± 1. In two large uncontrolled multicenter trials. Improvement in sleep and ability to concentrate was noted in the first 2 days of treatment with increasing improvements on subsequent days. No significant change in a lab environment as measured with activity monitor bracelets. officinalis L. This effect was seen with the 450 mg dose and increasing the dose was without further effect. placebo-controlled crossover study investigated the influence of 600 mg of a proprietary valerian preparation (Sedonium-LI 156. A more recent double-blind. Sleep onset was accelerated from an average of 15. The com- mercial preparation was not as effective as the extract. took from 3 to 9 tablets per day. placebo- controlled study.01). 1689 patients. 8 volunteers with mild insomnia were given 450 or 900 mg of extract. 80 elderly patients with behavioral disorders of nervous origin. 10 healthy male volunteers. valerenic acid. In summary. Subjects. showed no statistically significant effect on EEG from valer- ian extract (Leathwood and Chauffard 1982/3). In another study. by Leathwood and others (1982). Objective (NOSIE) and subjective parameters (von Zerssen’s well-being scale) were assessed. Sleep latency was improved in comparison with beginning baseline and in comparison with placebo. Fifty percent of those patients whose primary complaint was difficulty in con- centration reportedly were symptom free within the 10-day period. officinalis L. ethanol extract) in subjects with psychophysiological insomnia. it has been shown that the sedative and spasmolytic effects attributed to valerian are due to the activity of multiple constituents. The first of these studies. reported a subjective decrease in sleep latency of subjects at home. These preparations had no effect on night awakenings or dream recall. (Krieglstein and Grusla 1988). Leathwood and Chauffard 1985).001) and a decreased level of fatigue (P < 0.

and isoeugenyl-isovalerate were screened for central nervous system effects on mice upon ip administration (Hendriks and others 1985). valerenic acid. respectively. total sleep time. Valerenic acid also produced a dose-related increase in pentobarbital-induced sleep with 50 and 100 mg/kg ip (Hendriks and oth- ers 1985). As a result of these tests. or a combination of valerian and propranolol (Kohnen and Oswald 1988). No change was reported in night awakenings. 20 mg propranolol. Both valerian and the combination therapy led to less intense subjective feelings of “somatic arousal”.4% valepotriates. Valerian had no effect on stress-induced increases in heart rate caused by performing mathemati- cal calculations verbally. The above compounds at 20 mg/kg iv decreased rhythmic contractions and contractile force in ligated guinea pig ileum. All three medications were superior to placebo. menopausal neurosis. containing 0. The effects of valerian extract on stress were evaluated in a double-blind study using healthy volunteers. However. including cardiac palpitations. Comparison of the activity of valerian extracts in mice all but eliminated the the- ory that valepotriates are responsible for the sedative activity. but rather demonstrated a direct effect on the muscle tissue. In summary. less side effects were observed with the valerian preparations (10% of subjects) as compared to the group taking flunitrazepam (50% of subjects) (Gerhard and others 1996). The results of these studies have shown these preparations to have a significant positive effect on sleep disorders. Nepalese and Chinese valerian extracts containing 1. although there was a trend towards impairment of performance with the valerian-propranolol combination. The antispasmodic effects of the isolated essential oil component valeranone and valepotriates (isovaltrate. One final study compared the effects of two valerian prepa- rations (equivalent to 4 g) and flunitrazepam with placebo. improved in another 24%. Side effects of gastrointestinal upset and headache were reported in only 8 patients (Seifert 1988). almost doubled hexobarbital-induced sleep (P < 0. and only 6% of patients remained unchanged (Voight-Schmidt 1986). the authors described the activity of valerenic acid as a general central depressant rather than a neuroleptic or muscle relaxant. The authors considered the activity to be similar to that of papaverine and suggested an effect on calcium levels in the muscle tissue. the studies above have demonstrated statistically significant decreases in sleep latency and increases in sleep quality for poor sleepers.7% and 1. In vitro studies using ileum and stom- ach tissue showed that the effects of valeranone and didrovaltrate (10-5 to 10-4M) were not mediated through receptors of the cholinergic or adrenergic nervous system. Valerian treatment induced a slight improve- ment in a written concentration test. Numerous other studies on the effects of valerian on sleep have been conducted with commercial products containing various adjuncts. Symptoms were eliminated in 70% of subjects. or the normal levels of movement during the night.05% valepotri- ates. valeranone.other symptoms. producing ataxia at 50 mg/kg. and depres- sion was observed. Japanese valerian root Hokkai kesso. However. dream recall. Animal Studies The essential oil of valerian and the isolated components valerenal. the authors reported a decrease in rotorod and traction per- formance in mice given 100 mg/kg ip. although the propranolol and combination treatment reduced this physiological activation. Forty-eight men and women were divided into four treat- ment groups receiving either placebo. Isoeugenyl-iso- valerate did not appear to contribute much to the activity of the oil.168 patients treated by 982 German practitioners. but have not been reviewed here. 100 mg valerian extract. particularly lemon balm (Melissa officinalis) and passion flower (Passiflora spp. The essential oil showed sedative and/or muscle relaxant activity with the oxygenated components exhibiting more activity than the hydrocarbon fraction. showed no sedative activity in mice after oral administration of the equivalent of 10 g crude drug/kg. Valerenal and valerenic acid were more active than valeranone. valtrate. Similar results were reported in a study of 11.01) and approximately halved American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 15 . In a subsequent study on valerenic acid. and didrovaltrate) were demonstrated in a series of in vivo and in vitro studies using guinea pig smooth muscle tissue (Hazelhoff and oth- ers 1982).).

Immobility induced by a forced swimming test in rats was inhibited with 4 g/kg. at the same dose the extract prolonged thiopental induced anesthesia and was anticonvulsant against picrotoxin. Several researchers have linked the effects of valerian extracts and/or its components with an effect on the inhibitory neuro- transmitter GABA (Mennini and others 1993. was recently shown to displace radiolabeled GABA from its binding sites on synapto- somes isolated from rat brains (Santos and others 1994a). as was observed in mice treated with benzodiazepine and diazepam (a group of sedative-hyp- notics) at 2 mg/kg. Benzodiazepines exert their actions via this system. The constituents responsible for this effect were not identified.05) (Hikino and others 1980). However. 1994b). However. containing 55 mg valerenic acids/100 g extract. The usual concentration of glut- amine in the brain extracellular fluid is in the range of 0. Analysis also showed that the extract contained high amounts of glutamine (13 mM) which is able to cross the blood-brain barrier. GABA mediates sedation in the central nervous system. but valerenic acid was ruled out. Santos and others 1994a. An aqueous extract of valerian. An interaction with the GABA receptor is also suggested for the pineal hormone melatonin which exerts hypnotic and/or sedative effects. and the authors are investigating whether valerian extracts have any effect on rat brain amino acid levels in vivo. Glutamine has been shown in vitro to stimulate GABA synthesis in synaptosomes and brain slices. however. this study found no interac- tion between the extract and GABAA receptors (Fauteck and others 1996). stress-induced ulcer formation in mice (P < 0. A recent study found the valerian extract LI 156 was able to displace radiolabeled melatonin from its binding sites in the human cerebellum. In Vitro Studies Attempts have been made using in vitro assay techniques to delineate the mechanism of action for the sedative effects of valerian. Results with Hokkai kesso on hexobarbital-induced sleep in mice were repeated by another group who further profiled the psychotropic activity of this extract (Sakamoto and others 1992). These results led the authors to suggest that valerian may act as an antidepressant. the effect was small and required mM concen- trations. although they did suggest an interaction with the GABAA-benzodiazepine receptor complex (Hiller and Zetler 1996). thereby prolonging the inhibitory effect of GABA (Riedel and others 1982).5 mM. In contrast to the reports cited above. Ambulation and rearing was depressed in a dose-relat- ed manner after oral administration of 3 to 11 g/kg extract. Page 16 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . Analysis of the content of the extract for amino acids revealed that the extract itself contained GABA in suffi- cient quantity (4. Kessyl glycol acetates were suggested as the constituents of Hokkai kesso responsible for causing the increase in hexobarbital-induced sleep time. The effect was dose-dependent with an IC50 of 0. Valerenic acid and acetylvalerenic acid have been reported to inhibit GABA transaminase. The authors concluded that valerian does not exert the same type of anti-anxiety effect as diazepam. None of the valerian preparations showed any analgesic activity in a pressure/pain assay after oral administration of 10 g crude drug-equivalent/kg. they showed no activity in reducing stress-induced ulcer formation. However. but not pentetrazol or harman (ED50 of 24 mg root equivalent/kg body weight). the presence of GABA in the extract is unlikely to account for the activity of valerian in vivo because GABA does not cross the intact blood-brain barri- er. and reserpine-induced hypothermia in mice was reversed with 11 g/kg extract.5 mg/L.2 to 0.6 mM) to account for the displacement activity (Santos and others 1994b). An ethanolic extract of valerian given to male mice (dose equivalent to 400 mg root/kg ip body weight) did not produce overt sedation or tranquilization.

More recently. Hypotensive effects have also been reported. Pyrryl-α-methylketone exhibits both sedating and anesthetic activity. valerian alone or in com- bination with other sedative or antispasmodic herbs is specific for the symptomatic relief of insomnia. but to a less- er extent (Drobot’ko and others 1958). They did show an approx- imately 30% to 70% displacement of radiolabeled cyclohexyladenosine from adeno- sine receptors with high concentrations (0. the alkaloids l-hydroxypinoresinol. also showed activity. l-hydroxypinoresinol displayed a significant affinity for 5-HT1A receptors (IC50 of 2. menstrual cramps. Felter and Lloyd 1898. and spasms due to nervous tension. Hellemont 1986. Bradley 1992. and colic (Bradley 1992. nervous asthma. but little substan- tiation for this effect is provided in the literature (Rosecrans and others 1961). pinoresinol. Of the alkaloids studied. the underlying cause of the condition should be appropriately addressed. Actions Sedative. valerian extracts showed no binding to benzodiazepine recep- tors isolated from rat brains (Balduini and Cattabeni 1989). representing approximately 0.015% of the total alkaloids of valerian. Clinically it is used for a wide variety of conditions associated with the nervous system. Torssell and Wahlberg 1967). ESCOP 1990. anxiety. Leathwood and Chauffard 1985). Isolated alkaloids.01 to 1 mg/mL) of the hydroalcoholic extract. antispasmodic. nervous headaches. the management of infantile convulsions. as a gen- eral sleep aid and for disturbed sleep patterns (use 30 minutes prior to bed). Indications Based on a review of the primary pharmacologic literature. including nervous complaints due to menopause and hot flashes. GABAA-. were assayed for their affinity to 5-HT1A. valerine and chatinine. gastric spasms. Weiss 1988). symptomatic management of attention deficit hyperactivity disorder (ADHD). European Scientific Cooperative of Phytotherapy (ESCOP) 1990. In the traditional herbal literature. restlessness. as well as several valerian extracts.3 µM/l) and insignificant binding at benzodiazepam receptors. Valepotriates have been reported to promote dilation of the coronary artery and to be of potential benefit for reducing arryhthmias (Petkov 1979). As with the use of all sedatives. the alkaloids are considered to be of minor importance (Franck and others 1970. In another study. Otherwise. it has been used for patients who are pale. A number of studies have investigated the pharmacological activity of specific alkaloids. Valnet 1992. Johnson and Waller 1971. Isovaleramide is an effective central nervous system depressant at dosages as low as 30 mg/kg ip in mice (Balandrin and others 1996). American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 17 . and µ-opiate receptors (Bodesheim and Hölzl 1997). relaxant (Balderer and Borbély 1985. and asthenic. epileptic seizures or mild tremors. King offers insights into the proper use of valerian by stating that it is most effectual when used in patients with impaired cere- bral circulation associated with mental depression (King 1866). Stillé and others 1896. The alkaloid actinidine. Other Effects A preparation of crude alkaloids showed antibacterial activity against gram positive bacteria. Hendriks and others 1985. the presence of these compounds in commercial products is unlikely. As mentioned pre- viously. Traditionally. weak. Kohnen and Oswald 1988. Hazelhoff and others 1982. Further studies are needed to determine if these in vitro findings are of clinical rele- vance. benzodiazepine-. and pinoresinol-β-D- glucoside. nervine. has been reported to be a highly active inhibitor of cholinesterase (Torssell and Wahlberg 1967).

digoxin. Hot Infusion 1 cup or as needed up to 3 times daily (ESCOP 1993). 1994b). he had been using several medications including isosorbide dinitrate. Santos and others 1994a. He had a his- tory of coronary artery disease. furosemide.3-1 mL (10-20 drops) 1 or more times daily (up to 3 times) (ESCOP 1993). heart palpitations. a group of physicians from Duke University Medical Center presented a case history suggesting that serious cardiac complications (high output cardiac fail- ure) and delirium experienced by a patient may have been attributable to valerian withdrawal in a manner similar to benzodiazepine withdrawal (Garges and others 1998). Page 18 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . Substantiated Structure and Function Claim According to a review of the literature. and congestive heart failure and was admitted for an open biopsy of a lung nodule. healthy volunteers were treated with tablets containing valerian and hops. Tincture (1:5) 1-3 mL (20-60 drops) (Blumenthal and others 1998) as needed up to 3 times daily (ESCOP 1993). S A F E TY P R O F I L E Classification of the American Herbal Products Association Class 1: Herbs which can be safely consumed when used appropriately (McGuffin and others 1997). Osol and others 1947). Occasional headache and gastrointestinal distress were reported in one clinical study (Seifert 1988). An objectively measurable impairment of performance on the morning after medication occurred only in the flunitrazepam group. valerian can cause heart palpitations and nervousness. a syrup containing only valerian. The patient was using 530 mg to 2 g of valerian per dose 5 times daily for many years to help him sleep and relax and had discontinued use upon admission. Fluid Extract (1:1) 0. Riedel and others 1982. agitation. this study showed improved subjective self-assessment (more alert. hypertension. Side Effects In sensitive individuals. Upon admission. benazepril. a study was conducted to see whether this would also be the case with valerian preparations. valerian preparations equivalent in dosage and composition to those found to be effective in clinical human studies. excessive doses or large con- tinuous doses may cause nausea. In a placebo-controlled study. On the contrary. According to the older herbal literature.05-0.25 mL (2-6 drops) up to 2 times daily (Felter and Lloyd 1898). and dull the senses and response times (Culbreth 1917. Recently. Felter and Lloyd 1898). Cold Infusion 1 cup or as needed up to 3 times daily (ESCOP 1993. Dosages Powder 2-3 g or as needed up to 3 times daily (ESCOP 1993). sub- jective feeling of well-being) with the valerian and hops tablets and valerian syrup (Gerhard and others 1996). External 100 g per bath (Blumenthal and others 1998. promote relax- ation through an enhancement of GABA neurotransmission (Mennini and others 1993. or flunitrazepam (1 mg). diarrhea. Essential Oil 0. Because valerian is considered to exert a benzodiazepine-like action through enhancement of GABA neurotransmission and because a reversal of symptoms was observed with administration of benzodiazepine. headache. Weiss 1988). the reporting physicians considered there to be a strong correlation between the adverse event and valerian withdrawal. more active. Because benzodiazepines taken to aid in sleep can impair alertness the morning after administration.

At 2 mg/kg po an aqueous alkaline extract (5 to 6:1) increased thiopen- tal-induced sleeping time in mice by a factor of 1. Consumption of valerian products have been implicated in at least five cases of liver toxicity (see Toxicology). Hendriks and others 1985: Rosecrans and others 1961). The acute crisis occurred after administra- tion of naloxone and subsequently stabilized over the course of 3 days. isovaltrate. Part of the in vitro cytotoxicity of valepotriates may be due to their ability to interact with thiol-containing enzymes (Bos and others 1998b). potassium. Those of the diene type displayed the highest cytotoxicity with IC50 values slightly higher than those of the cytotoxic agent cisplatin (GLC4: 1µ 3-fold less toxic.6-fold increase was observed. Those of the monoene type were found to be 2. and maaliol) were comparable to that of valerenic acid (see Table 1) (Bos and others 1998b). a 4. such as valtrate and 30-fold less toxic than their parent com- pounds (see Table 2). In older literature. After being discharged the patient continued using valerian and was stable at his 2-month and 5- month assessments. Additional interventions were applied in the course of the biopsy. These data are as follows. The cytotoxic potential of valerenic acid and its derivatives. Two groups of valepotriates are distinguished: those of the diene type (val- trate. Pregnancy. as well as valepotriates and their derivatives. COLO 320: 3 µM) which was used as a comparison. and methyl valerenate) displayed a low toxicity with IC50 values between 100 and 200 µM. and vitamins. As previously stated. lovastatin.aspirin. were found to be 10. Mutagenicity. baldrinal and homobaldrinal. cryptofauronol. Contraindications None cited in the literature (Blumenthal and others 1998.6 (P ≤ 0. The cytotoxic potential of other compounds of the essential oil (valeranone. monoacetate.7-fold increase was observed with concomitant use of chlorpromazine (4.01). patchouli alcohol. and the decomposition products of valepotriates. kessoglycl. was investigated against a human small cell lung cancer cell line (GLC4) and a human colorectal cancer cell line (COLO 320) using the microculture tetrazolium (MTT) assay (Bos and others 1998b). It has also been reported that valerian has been used in conjunction with bromides and other sedatives. it was reported that atropine decreases the hypotensive activity of valerian by 50% (Rosecrans and others 1961). Also reported in older liter- ature is the ability of valepotriates (20 mg/kg iv) to reduce vasopressin and barium- induced arrhythmia in rabbits (Petkov 1979). Bradley 1992). Valerenic acid and its derivatives (acetoxyvalerenic acid. and at 200 mg/kg po a 7. these compounds degrade rapidly and are typically not found in commercial preparations. American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 19 . and Reproductive Toxicity There is a significant amount of literature regarding the mutagenic potential of vale- potriates. ibuprofen.0 mg/kg po) (Leuschner and others 1993). Specific data regarding the interaction are lacking (Evans 1989). contain an epoxide group and thus possess alkylating properties. and acevaltrate) and those of the monoene type (didrovaltrate and isovaleroxyhydroxydidrovaltrate). Valepotriates. zinc. hydroxyvalerenic acid. Interactions Valerian and some valerian preparations have been shown to potentiate the effects of barbiturates (Bounthanh and others 1980. As a comparison. kessoglycl diacetate.

valepotriates are considered to be of little toxicological concern because they are absent from most commercial products. These compounds are unstable and deteriorate rapidly in the intestines and are poorly absorbed (ESCOP 1990. Table 1 Cytotoxicity of constituents of Valeriana officinalis (IC50 values [µM] ± standard error [95% confidence interval]. Reprinted with permission of Phytomedicine. Hänsel 1990. Despite these findings.1 3.2 7.1 5. Hude and others 1985.8 Acevaltrate 1. n = 3) Constituent GLC4 COLO 320 Valepotriates Valtrate 1.2 Isovaleroxyhydroxydidrovaltrate 2.1 1.1 Valerenic Acids Valerenic acid 127 ± 9 124 ± 8 Acetoxyvalerenic acid 111 ± 8 124 ± 7 Hydroxyvalerenic acid 123 ± 4 165 ± 3 Methyl valerenate 115 ± 2 183 ± 14 Source: Bos and others (1998b).0 ± 0.5 Didrovaltrate 8. 1992. and 24 mg/kg ip for 30 days to female rats before and during pregnancy produced no signif- icant toxic effects.3 ± 0. Significant degradation of the valepotriates occurs during extraction by per- colation.6 ± 0.2 ± 0. in terms of the dilution causing 50% effect in the MTT assay) Fresh Stored GLC4 1123 ± 57 311 ± 24 COLO 320 531 ± 17 145 ± 8 Source: Bos and others (1998b).1 3.4 ± 0. n = 3.2 Baldrinals Baldrinal 53 ± 2 111 ± 5 Homobaldrinal 31 ± 2 57 ± 10 Isovaltral 0.4 ± 0.3 Isovaltrate 2. No significant negative effects have been Page 20 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . An internal examination of fetuses indicated an increase in retard- ed ossification.2 ± 0. Table 2 Cytotoxicity of Valeriana officinalis tinctures (1:5. though no changes were detected in postnatal development of the off- spring (Tufik and others 1994). These extracts contained significantly lower concentrations of the compounds investigated than the crude material. Keochanthala-Bounthanh and others 1990. These same researchers conducted similar investigations to determine the cyto- toxic potential of 70% ethanol extracts (1:5) (see Table 2).4 ± 0. 1993).5 ± 0. 1986. 15% valtrate. Hendriks and others 1985).2 ± 0. Another group of researchers found that a mixture of isolated valepotriates (80% dihydrovaltrate.9 ± 0.4 ± 0. 12. Reprinted with permission of Phytomedicine. and 5% acevaltrate) administered orally at 6. A number of other studies have reported on the cytotoxic and mutagenic poten- tial of valepotriates in in vitro cell systems and on the inhibition of DNA and protein synthesis in in vitro cultured mammalian cells (Bounthanh and others 1981.4 15. and almost complete deterioration of the valepotriates occurs within 2 months of the extract being stored (Bos and others 1998b). 70% ethanol) (IC50 values ± stan- dard error [95% confidence interval].

Lactation Specific data are lacking. hyoscine hydrobromide (0. double-blind study with 54 partici- pants. tremor of the hands and feet. concentration. Mutagenicity. Other researchers reported a slight. but otherwise the physical examination was normal except for a bilateral widening of the pupils. As with other sedatives. The preparation also did not increase impairment due to alcohol with a blood level of 0.5% (Albrecht and others 1995). According to the clinical literature of Eclectic physician Finley Ellingwood. and none have been reported in human clinical studies. nausea” and large doses of oil can cause “increase of urine with slow pulse and drowsiness ending in deep sleep. agitation. motility and reflex excitability. Precautions May cause drowsiness. pervert- ed vision. giddiness. and cyproheptadine hydrochloride (2 mg). Liver enzymes were subsequently found to be normal. but statistically significant impairment of vig- ilance and retardation in processing of complex information in subjects consuming a higher dose of valerian (equivalent to 4 g containing a minimum of 1. Carcinogenicity See Pregnancy. All symptoms resolved within 24 hours of admittance (Willey and others 1995). A dose of 2 tablets twice daily of a 640 mg blend of valerian root extract and lemon balm leaf extract did not impair reaction time. or attentiveness as assessed by a battery of psychometric tests. The blood pres- sure appeared to be slightly low. no negative effects are to be expected. Overdose In an attempted suicide. or if engaged in activities requiring men- tal alertness.2 mg of sesquiterpenes) (Gerhard and others 1996). if operating heavy machinery. large doses of valerian can “stimulate the brain causing headache. spasmodic abdominal pain. Influence on Driving The effect of a proprietary valerian and lemon balm preparation (Euvegal®) on the psychomotor and mental performance required for operation of machinery or driving of vehicles was tested in a placebo-controlled. chest tightness. Thirty min- utes after ingestion. causes central paral- ysis” (Ellingwood and Lloyd 1900). the subject complained of fatigue.25 mg). Average dosages consumed were approximately 33 times higher than the recom- mended dose. Central nervous system depression and anticholinergic poi- soning were reported in patients consuming a product containing valerian (75 mg). One other report of supposed valerian overdose has been published as a letter to the editor (Chan 1998).reported in toxicologic research with animals. and if the dose be large enough. and Reproductive Toxicity. 20 g of crude valerian powder was consumed. restlessness. American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 21 . and lightheadedness. care should be taken when using valerian in the daytime while driving. Based on a review of the available literature. The patient was treated with 2 doses of activated charcoal (approxi- mately 400 mg each). abrupt discontinuation after long-term use may result in with- drawal symptoms (Garges and others 1998). It lessens sensibility. Beacause valerian is considered to work in a manner similar to benzodiazepines.

No reports of chronic toxicity have been reported when valerian is used at recommend- ed therapeutic doses. an LD50 for an ethanol extract of unde- fined strength was reported to be 3. but failed to produce any significant toxicity (see Overdose) (Willey and others 1995). arterial pressure. no differences in growth. In an early toxicologic study of the essential oil. With oral doses of an alcohol extract equivalent to 300 and 600 mg/kg. At daily doses of 400-600 mg/kg ip for 45 days. The LD50 for some valerian preparations and specific compounds has been established (see Table 3). blood. In an early study. Consumption of approximately 20 g (approximately 10 times the recommended therapeutic dosage) resulted in marked side effects. Toxicology Acute toxicity of valerian is rare. therefore adulteration with ger- mander is unlikely. Subsequently. the botanical germander Teucrium chamaedrys L. 150-200 mg/kg caused muscle spasms. four other cases of hepatotoxicity which may have been related to long-term use of valerian have been reported. There have been a number of reports associating consumption of valerian prod- ucts with hepatotoxicity. These products did not contain skullcap. MacGregor and others reported on the hepatotoxicity of valerian preparations which also reportedly contained skullcap Scutellaria lateriflora (MacGregor and others 1989).. Table 3 Known LD50 values for valerian Constituent LD50 mg/kg Essential oil 15 g/kg rats (Skramlik 1959) Ethanol extract 3. and 400 mg/kg caused heavy convulsions and death within 24 hours (Hendriks and others 1985). 100 mg/kg caused ataxia. However. including oils of peppermint and anise (Skramlik 1959). a LD50 of 15g/kg in rats was reported. commonly adulterates the skullcap market and may have been the causative agent. no significant changes in weight. In studies with pure valerenic acid. hematological nor biochemical parameters were observed (Fehri and others 1991).3 g/kg ip (Rosecrans and others 1961) Valeranone > 3 g/kg orally administered acute in rats and mice (Rücker and others 1978) Valerenic acid Approximately 300 mg/kg ip in mice (Hendriks and others 1985) Page 22 American Herbal Pharmacopoeia™ • Valerian Root • April 1999 . 50 mg/kg reduced spontaneous motility. The effect may have been idiosyncratic because a range of doses were used and consumption of products with greater amounts of valerian have not been implicated (Shaw and others 1997). weight of key organs. a known hepatotoxic agent. or urine were observed when compared to controls (Rosecrans and others 1961). It is not clear whether these different find- ings may be related to the type of extract used or different formulations.3 g/kg ip in rats. The oil was found to be the least toxic of 27 essential oils studied.

irritability. I N T E R N AT I O N A L S TAT U S United States Regulated as a dietary supplement. Schedule 1. innerer Unruhe. Ein-und Durchschlafstörungen (stressful states. Indications include: Bei spannungszuständen.3% volatile oil for the cut material. United Kingdom Included in the British Pharmacopoeia. antispasmodic. British Pharmacopoeia 1998).5% essential oil. Approved by the Swiss registration authority for medicines as a sedative when used singly and in combinations. European Pharmacopoeia Required to contain not less than 0.3% (V/w) volatile oil for the cut material (European Pharmacopoeia 1998). ESCOP Cited as a sedative. Nervosiät. Required to contain not less than 0. Council of Europe Approved as a flavoring agent (Bradley 1992). Commission E: Approved for sleep disorders caused by nervous conditions (Blumenthal and others 1998). France Included in the pharmacopoeia of France.5% essential oil. Switzerland Included in the pharmacopoeia of Switzerland. and dried extract are included in the pharmacopoeia of Germany. Germany The crude herb. trouble sleeping through the night). A Drug Identification Number (DIN) is required when claims are present. tincture. Generally recognized as safe (GRAS) as a flavor- ing agent. Required to contain 0. Sold in pharmacies and drogueries. Reizbarkeit. Canada Approved as a traditional herbal sleep aid.5% essential oil (Pharmacopée Française 1987). Required to contain not less than 0. Belgium Approved for the following indications: Traditionally used for reducing excitability in adults and children in cases of sleep disorders. General Sales List. American Herbal Pharmacopoeia™ • Valerian Root • April 1999 Page 23 .5% essential oil (Pharmacopoea Italica 1991). and relaxant (ESCOP 1990). Approved as a sedative. although its activity has not been proven in accordance with the current evaluation criteria for medicines (Bradley 1992). Regulated as a food supplement without claims.5% (V/w) volatile oil for the whole root and not less than 0. particularly in case of minor sleep disorders (Bradley 1992). Table A(R1a) (Bradley 1992. Tincture: 0. The crude herb is required to contain not less than 0. Australia Listed in the Australian Register of Therapeutic Goods. internal anxiety. Italy Included in the pharmacopoeia of Italy. Austria Included in the pharmacopoeia of Austria (Österreichisches Arzneibuch 1990).06% essential oil (Pharmacopoea Helvetica 8 1997). Approved for the following indications: Traditional medicine for the symptomatic treatment of nervous disorders in adults and children. Required to contain not less than 0. nervousness.5% (V/w) volatile oil for the whole root and not less than 0.

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Mutagenicity. and Reproductive Toxicity Lactation Carcinogenicity Influence on Driving Precautions Overdose Toxicology International Status 23 References 24 A H P American Herbal Pharmacopoeia™ PO Box 5159 Santa Cruz.TA B L E OF CONTENTS Nomenclature 1 Botanical Nomenclature Botanical Family Definition Common Names History 1 Identification 2 Botanical Identification Macroscopic Identification Microscopic Identification Commercial Sources and Handling 5 Collection Cultivation Drying Handling Storage Adulterants Preparations Constituents 7 Analytical 8 Spot Test Assay for Essential Oil Thin Layer Chromatography ( Website: herbal-ahp. CA 95063 US Tel: 831-461-6335 Fax: 831-475-6219 Email: . HPTLC) High Performance Liquid Chromatography (HPLC) Qualitative Standards Therapeutics 13 Pharmacokinetics Pharmacodynamics Effect on Sleep Human Clinical Studies Animal Studies In vitro Studies Other Effects Actions Indications Substantiated Structure and Function Claim Dosages Safety Profile 18 Classification of the American Herbal Products Association Side Effects Contraindications Interactions Pregnancy.