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WHO Monographs on Selected Medicinal Plants - Volume 1
(1999; 295 pages) View the PDF document
Table of Contents
View the documentAcknowledgements
View the documentIntroduction
View the documentBulbus Allii Cepae
View the documentBulbus Allii Sativi
View the documentAloe
View the documentAloe Vera Gel
View the documentRadix Astragali
View the documentFructus Bruceae
View the documentRadix Bupleuri
View the documentHerba Centellae
View the documentFlos Chamomillae
View the documentCortex Cinnamomi
View the documentRhizoma Coptidis
View the documentRhizoma Curcumae Longae
View the documentRadix Echinaceae
View the documentHerba Echinaceae Purpureae
View the documentHerba Ephedrae
View the documentFolium Ginkgo
View the documentRadix Ginseng
View the documentRadix Glycyrrhizae
View the documentRadix Paeoniae
View the documentSemen Plantaginis
View the documentRadix Platycodi
View the documentRadix Rauwolfiae
View the documentRhizoma Rhei
View the documentFolium Sennae
View the documentFructus Sennae
View the documentHerba Thymi
View the documentRadix Valerianae
View the documentRhizoma Zingiberis
View the documentAnnex. Participants in the WHO Consultation on Selected Medicinal Plants
 

Radix Valerianae

Definition

Radix Valerianae consists of the subterranean parts of Valeriana officinalis L. (sensu lato) (Valerianaceae)1 including the rhizomes, roots, and stolons, carefully dried at a temperature below 40 °C (1–6).

1 Approximately 200 Valeriana species are available, but only a few are or were used medicinally, such as V. fauriei Briquet (Japanese Valerian) (7), V. wallichii DC (Indian Valerian) and V. edulis Nutt ex. Torr. & Gray (8). In commerce, V. edulis Nutt. ex Torr. & Gray is known as "Valeriana mexicana". Plants bearing this common name should not be confused with V. mexicana DC., which is in fact V. sorbifolia H.B.K. var. mexicana (DC) F.G. Mey.

Synonyms

Valeriana alternifolia Ledeb., Valeriana excelsa Poir., Valeriana sylvestris Grosch. (1).

Selected vernacular names

All heal, akar pulepandak, amantilla, balderbrackenwurzel, baldrian, Baldrianwurzel, cat's love, cat's valerian, fragrant valerian, garden heliotrope, great wild valerian, ka-no-ko-so, Katzenwurzel, kesso root, kissokon, kuanyexiccao, luj, nard, ntiv, racine de valeriane, St. George's herb, setwall, txham laaj, valerian fragrant, valerian, valeriana, valeriana extranjera, valeriana rhizome, valeriane, vandal root, waliryana, wild valerian (8–11).

Descriptions

A tall perennial herb whose underground portion consists of a vertical rhizome bearing numerous rootlets and one or more stolons. The aerial portion consists of a cylindrical hollow, channelled stem attaining 2m in height, branched in the terminal region, bearing opposite exstipulate, pinnatisect, cauline leaves with clasping petioles. The inflorescence consists of racemes of cymes whose flowers are small, white, or pink. The fruits are oblong-ovate, 4-ridged, single-seeded achenes (1, 9).

Valeriana officinalis (sensu lato) is an extremely polymorphous complex of subspecies. The basic type is diploid, 2n = 14, (V. officinalis) and other subspecies have very similar characteristics: V. officinalis ssp. collina (Wallr.) Nyman (2n = 28) has leaves with 15–27 folioles, all of the same width, and V. officinalis ssp. sambucifolia (Mikan f.) Celak, V. excelsa Poiret (2n = 56) has leaves with 5– 9 folioles, with the apical one clearly larger than the others. In contrast to the other subspecies, the rhizome of the latter is clearly stoloniferous (epigenous and hypnogenous stolons). V. repens Host. (equivalent to V. procurrens Wallr.) could be considered a fourth species, according to the Flora Europaea. Often appended to this species are taxonomic groups of uncertain status and limited distribution (e.g. V. salina Pleigel or V. versifolia Brügger) (12).

Plant material of interest: dried roots, rhizomes and stolons

General appearance

Rhizome, erect, entire or usually cut into 2–4 longitudinal pieces, 2–5cm long, 1–3cm thick; externally, dull yellowish brown or dark brown, sometimes crowned by the remains of stem bases and scale leaves, and bears occasional, short, horizontal branches (stolons), and numerous rootlets or their circular scars; fracture, short and horny. Internally, whitish, with an irregular outline, occasionally hollow and exhibiting a comparatively narrow ark traversed, here and there, by root-traces, and separated by a dark line, the cambium, from a ring, small xylem bundles surrounding a central pith. Roots, numerous, slender, cylindrical, usually plump; 2–12cm but mostly 8–10cm long, 0.5–2mm in diameter; externally, greyish brown to brownish yellow, longitudinally striated, with fibrous lateral rootlets; brittle; internally, showing a wide bark and a narrow central stele (1, 9).

Organoleptic properties

Odour, characteristic, penetrating valeric acid-like, becoming stronger on aging; taste, sweetish initially, becoming camphoraceous and somewhat bitter (1–5, 9).

Microscopic characteristics

Rhizome, with epidermis of polygonal cells, having the outer walls slightly thickened; cork, immediately below the epidermis, of up to 7 layers of slightly suberized, brownish, large polygonal cells; cortex, parenchymatous with rather thick-walled parenchyma, containing numerous starch granules and traversed by numerous root-traces; endodermis of a single layer of tangentially elongated cells containing globules of volatile oil; pericycle, parenchymatous; vascular bundles, collateral, in a ring and surrounding a very large parenchymatous pith, containing starch granules and occasional scattered groups of sclereids with thick pitted walls and narrow lumen; xylem, with slender, annular, spiral, and pitted vessels, in small numbers. Branches similar to rhizome but with a prominent endodermis and a well-defined ring of vascular bundles, showing secondary thickening.

Root, with piliferous layer, of papillosed cells, some developed into root hairs; exodermis, or a single layer of quadrangular to polygonal cells, with suberized walls, and containing globules of volatile oil; cortex, parenchymatous, with numerous starch granules, the outermost cells containing globules of volatile oil; endodermis, of 1 layer of cells with thickened radial walls; primary xylem, of 3–11 arches surrounding a small central parenchymatous pith containing starch granules, 5–15µm in diameter, sometimes showing a cleft or stellate hilum; the compound granules, with 2–6 components, up to 20µm in diameter. Older roots show a pith of starch-bearing parenchyma, vascular bundles with secondary thickening and a periderm originating in the piliferous layer (1, 4, 9, 13).

Powdered plant material

Light brown and characterized by numerous fragments of parenchyma with round or elongated cells and containing starch granules, 5–15µm in diameter, sometimes showing a cleft or stellate hilum, the compound granules, with 2–6 components, up to 20µm in diameter; cells containing light brown resin; rectangular sclereids with pitted walls, 5–15µm thick; xylem, isolated or in noncompact bundles, 10–50µm in diameter; some absorbing root hairs and cork fragments are also present (4).

Geographical distribution

Valeriana officinalis (sensu lato) is an extremely polymorphous complex of subspecies with natural populations dispersed throughout temperate and sub-polar Eurasian zones. The species is common in damp woods, ditches, and along streams in Europe, and is cultivated as a medicinal plant, especially in Belgium, England, eastern Europe, France, Germany, the Netherlands, the Russian Federation, and the United States of America (1, 9, 10, 12).

General identity tests

Macroscopic, microscopic, organoleptic, and microchemical examination (1–6, 9, 13); and by thin-layer chromatography for the presence of valerenic acid, acetoxyvalerenic acid, valtrate, and isovaltrate (15).

Purity tests

Microbiology

The test for Salmonella spp. in Radix Valerianae products should be negative. The maximum acceptable limits of other microorganisms are as follows (14– 16). For preparation of decoction: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g. Preparations for internal use: aerobic bacteria-not more than 105/g or ml; fungi-not more than 104/g or ml; enterobacteria and certain Gram-negative bacteria-not more than 103/g or ml; Escherichia coli-0/g or ml.

Foreign organic matter

Not more than 5% (1).

Acid-insoluble ash

Not more than 7% (1–5).

Dilute ethanol-soluble extractive

Not less than 15% (2–5).

Pesticide residues

To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin for Radix Valerianae is not more than 0.05 mg/kg (16). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (14) and guidelines for predicting dietary intake of pesticide residues (17).

Heavy metals

Recommended lead and cadmium levels are no more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (14).

Radioactive residues

For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (14).

Other purity tests

Chemical, moisture, total ash and water-soluble extractive tests are to be established in accordance with national standards.

Chemical assays

Contains not less than 0.5% v/w of essential oil (35), quantitatively determined by distillation (2–5). Content of individual constituents including valepotriates, valerenic acids and valerenal, determined by high-performance liquid (18, 19) or gas–liquid (20) chromatographic methods.

Major chemical constituents

The chemical composition of Radix Valerianae varies greatly depending on the subspecies, variety, age of the plant, growing conditions, and type and age of the extract. The volatile oil (ranges 0.2–2.8%) contains bornyl acetate and bornyl isovalerate as the principal components. Other significant constituents include β-caryophyllene, valeranone, valerenal, valerenic acid, and other sesquiterpenoids and monoterpenes (12, 21). The co-occurrence of three cyclopentane-sesquiterpenoids (valerenic acid, acetoxyvalerenic acid, and valerenal) is confined to V. officinalis and permits its distinction from V. edulis and V. wallichii (12). The various subspecies of V. officinalis have different compositions of volatile oil and, for example, average bornyl acetate content varies from 35% in V. officinalis ssp. pratensis to 0.45% in V. officinalis ssp. illyrica (12).

A second important group of constituents (0.05–0.67% range) is a series of non-glycosidic bicyclic iridoid monoterpene epoxy-esters known as the valepotriates. The major valepotriates are valtrate and isovaltrate (which usually represent more than 90% of the valepotriate content). Smaller amounts of dihydrovaltrate, isovaleroxy-hydroxydihydrovaltrate, 1-acevaltrate or others are present (8, 12). The valepotriates are rather unstable owing to their epoxide structure, and losses occur fairly rapidly on storage or processing, especially if the drug is not carefully dried. Principal degradation products are baldrinal, homobaldrinal, and valtroxal (8).

bornyl acetate

R = Ac

bornyl isovalerate

R = iVal

 

R1

R

valerenal

H

CHO

valerenic acid

H

CO2H

acetoxyvalerenic acid

OAc

CO2H

 

R1

R2

R3

valtrate

iVal

iVal

Ac

isovaltrate

iVal

Ac

iVal

acevaltrate

iVal

AcOiVal

Ac

baldrinal

R = Ac

homobaldrinal

R = iVal

Dosage forms

Internal use as the expressed juice, tincture, extracts, and other galenical preparations (8, 22). External use as a bath additive (22). Store in tightly closed containers, in a cool dry place, protected from light (1–6).

Medicinal uses

Uses supported by clinical data

As a mild sedative and sleep-promoting agent (8, 12, 2225). The drug is often used as a milder alternative or a possible substitute for stronger synthetic sedatives, such as the benzodiazepines, in the treatment of states of nervous excitation and anxiety-induced sleep disturbances (22–25).

Uses described in pharmacopoeias and in traditional systems of medicine

As a digestive aid, and an adjuvant in spasmolytic states of smooth muscle and gastrointestinal pains of nervous origin (8, 12). When associated with papaverine, belladonna, and other spasmolytics, Radix Valerianae has been shown to be useful as an adjuvant in spastic states of smooth muscle such as spastic colitis (8).

Uses described in folk medicine, not supported by experimental or clinical data

To treat epilepsy, gum sores, headaches, nausea, sluggish liver, urinary tract disorders, vaginal yeast infections, and throat inflammations; and as an emmenagogue, antiperspirant, antidote to poisons, diuretic, anodyne, and a decoction for colds (5, 8).

Pharmacology

Experimental pharmacology

The sedative activity of V. officinalis has been demonstrated both in vitro and in vivo. In vitro studies have demonstrated the binding of valerian extracts to GABA (γ-aminobutyric acid) receptors, adenosine receptors and the barbiturate and benzodiazepine receptors (8, 26). Both hydroalcoholic and aqueous total extracts show affinity for the GABA-A receptors, but there is no clear correlation between any of the known chemical components isolated from Radix Valerianae and GABA-A binding activity (8). Aqueous extracts of the roots of V. officinalis inhibit re-uptake and stimulate the release of radiolabelled GABA in the synaptosomes isolated from rat brain cortex (27, 28). This activity may increase the extracellular concentration of GABA in the synaptic cleft, and thereby enhance the biochemical and behavioural effects of GABA (8, 27). Interestingly, GABA has been found in extracts of V. officinalis and appears to be responsible for this activity (29). The valtrates, and in particular dihydrovaltrate, also show some affinity for both the barbiturate receptors and the peripheral benzodiazepine receptors (8).

In vivo studies suggest that the sedative properties of the drug may be due to high concentrations of glutamine in the extracts (29). Glutamine is able to cross the blood–brain barrier, where it is taken up by nerve terminals and subse- quently metabolized to GABA (29). The addition of exogenous glutamine stimulates GABA synthesis in synaptosomes and rat brain slices (29).

The spasmolytic activity of the valepotriates is principally due to valtrate or dihydrovaltrate (30). These agents act on centres of the central nervous system and through direct relaxation of smooth muscle (31), apparently by modulating Ca2+ entry into the cells or by binding to smooth muscle (8, 32).

Clinical pharmacology

A number of clinical investigations have demonstrated the effectiveness of Radix Valerianae as a sleep aid and minor sedative (8, 22–25). In a double-blind study, valerian (450mg or 900mg of an aqueous root extract) significantly decreased sleep latency as compared with a placebo (23). The higher dose of valerian did not further decrease sleep latency (23). Additional clinical studies have demonstrated that an aqueous extract of valerian root significantly increased sleep quality, in poor and irregular sleepers, but it had no effect on night awakenings or dream recall (24). The use of Radix Valerianae appears to increase slow-wave sleep in patients with low baseline values, without altering rapid eye movement (REM) sleep (24).

While extracts of the drug have been clearly shown to depress central nervous system activity, the identity of the active constituents still remains controversial. Neither the valepotriates, nor the sesquiterpenes valerenic acid and valeranone, nor the volatile oil alone can account for the overall sedative activity of the plant (8, 33). It has been suggested that the baldrinals, degradation products of the valepotriates, may be responsible (26). Currently, it is still not known whether the activity of Radix Valerianae extracts resides in one compound, a group of compounds, or some unknown compound, or is due to a synergistic effect.

Contraindications

Radix Valerianae should not be used during pregnancy or lactation (31, 34).

Warnings

No information available.

Precautions

General

May cause drowsiness. Those affected should not drive or operate machinery. Although no interaction between valerian and alcohol has been demonstrated clinically, as a precautionary measure patients should avoid consuming alcoholic beverages or other sedatives in conjunction with Radix Valerianae (31).

Carcinogenesis, mutagenesis, impairment of fertility

Some concern has been expressed over the cytotoxicity of the valepotriates. Cytotoxicity has been demonstrated in vitro but not in vivo, even in doses of 1350mg/kg (35). Some of the valepotriates demonstrate alkylating activity in vitro. However, because the compounds decompose rapidly in the stored drug, there is no cause for concern (35). The valepotriates are also poorly absorbed and are rapidly metabolized to the baldrinals (26), which have better sedating effects. In vitro, the baldrinals are less toxic than the valepotriates, but in vivo they are more cytotoxic because they are more readily absorbed by the intestine. Baldrinals have been detected at levels up to 0.988mg/dose in commercial preparations standardized with respect to the concentration of valepotriates and may be of cytotoxic concern (36).

Pregnancy: teratogenic effects

Prolonged oral administration of valepotriates did not produce any teratogenic effects (8, 37).

Pregnancy: non-teratogenic effects

The safety of Radix Valerianae during pregnancy has not been established; therefore it should not be administered during pregnancy.

Nursing mothers

Excretion of Radix Valerianae into breast milk and its effects on the newborn infant have not been established; therefore it should not be administered during lactation.

Paediatric use

Radix Valerianae preparations should not be used for children less than 12 years of age without medical supervision (34).

Other precautions

No information on general precautions or drug interactions or drug and laboratory test interactions was found.

Adverse reactions

Minor side-effects have been associated with chronic use of Radix Valerianae and include headaches, excitability, uneasiness, and insomnia. Very large doses may cause bradycardia and arrhythmias, and decrease intestinal motility (38). The recommended first aid is gastric lavage, charcoal powder, and sodium sulfate (38). Doses up to 20 times the recommended therapeutic dose have been reported to cause only mild symptoms which resolved within 24 h (38). Four cases of liver damage have been associated with use of preparations containing Radix Valerianae (39). However, in all cases the patients were taking a combination herbal product containing four different plant species and thus a causal relationship to the intake of valerian is extremely doubtful.

Posology

Dried root and rhizome, 2–3g drug per cup by oral infusion, 1–5 times per day, up to a total of 10 g and preparations correspondingly (6, 22). Tincture (1:5, 70% ethanol), 0.5–1 teaspoon (1–3ml), once to several times a day. External use, 100 g drug for a full bath (22).

References

1. African pharmacopoeia, 1st ed. Lagos, Organization of African Unity, Scientific, Technical & Research Commission, 1985.

2. British pharmacopoeia. London, Her Majesty's Stationery Office, 1988.

3. Deutsches Arzneibuch 1996. Stuttgart, Deutscher Apotheker Verlag, 1996.

4. European pharmacopoeia, 2nd ed. Strasbourg, Council of Europe, 1995.

5. Pharmacopée française. Paris, Adrapharm, 1996.

6. Pharmacopoea hungarica VII. Budapest, Medicina konyvkiado, 1986.

7. The Japanese pharmacopoeia XIII. Tokyo, Ministry of Health and Welfare, 1996.

8. Morazzoni P, Bombardelli E. Valeriana officinalis: traditional use and recent evaluation of activity. Fitoterapia, 1995, 66:99–112.

9. Youngken HW. Textbook of pharmacognosy, 6th ed. Philadelphia, Blakiston, 1950.

10. Bisset NG. Max Wichtl's herbal drugs & phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994.

11. Farnsworth, NR. ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, March 15, 1995 production (an on-line database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network (STN) of Chemical Abstracts Services).

12. Bruneton J. Pharmacology, phytochemistry, medicinal plants. Paris, Lavoisier, 1995.

13. Jackson BP, Snowden DW. Atlas of microscopy of medicinal plants, culinary herbs and spices. Boca Raton, FL, CRC Press, 1990.

14. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.

15. Deutsches Arzneibuch 1996. Vol. 2. Methoden der Biologie. Stuttgart, Deutscher Apotheker Verlag, 1996.

16. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1997.

17. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (unpublished document WHO/FSF/FOS/97.7; available from Food Safety, WHO, 1211 Geneva 27, Switzerland).

18. Feytag WE. Bestimmung von Valerensäuren und Valerenal neben Valepotriaten in Valeriana officinalis durch HPLC. Pharmazeutische Zeitung, 1983, 128:2869–2871.

19. van Meer JH, Labadie RP. Straight-phase and reverse phase high-performance liquid chromatographic separations of valepotriate isomers and homologues. Journal of chromatography, 1981, 205:206–212.

20. Graf E, Bornkessel B. Analytische und pharmazeutisch-technologische Versuche mit Baldrian. Deutsche Apotheker Zeitung, 1978, 118:503–505.

21. Hänsel R, Schultz J. Valerensäuren und Valerenal als Leitstoffe des offizinellen Baldrians. Bestimmung mittels HPLC-Technik. Deutsche Apotheker Zeitung, 1982, 122:333–340.

22. Leathwood PD, Chauffard F. Quantifying the effects of mild sedatives. Journal of psychological research, 1982/1983, 17:115.

23. Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta medica, 1985, 2:144–148.

24. Schultz H, Stolz C, Muller J. The effect of valerian extract on sleep polygraphy in poor sleepers: a pilot study. Pharmacopsychiatry, 1994, 27:147–151.

25. Balderer G, Borbely A. Effect of valerian on human sleep. Psychopharmacology, 1985, 87:406–409.

26. Wagner H, Jurcic K, Schaette R. Comparative studies on the sedative action of Valeriana extracts, valepotriates and their degradation products. Planta medica, 1980, 37:358–362.

27. Santos MS et al. Synaptosomal GABA release as influenced by valerian root extract, involvement of the GABA carrier. Archives of international pharmacodynamics, 1994, 327:220–231.

28. Santos MS et al. An aqueous extract of valerian influences the transport of GABA in synaptosomes. Planta medica, 1994, 60:278–279.

29. Santos MS et al. The amount of GABA present in the aqueous extracts of valerian is sufficient to account for 3H-GABA release in synaptosomes. Planta medica, 1994, 60:475–476.

30. Wagner H, Jurcic K. On the spasmolytic activity of Valeriana extracts. Planta medica, 1979, 37:84–89.

31. Houghton P. Herbal products: valerian. Pharmacy journal, 1994, 253:95–96.

32. Hazelhoff B, Malingre TM, Meijer DKF. Antispasmodic effects of Valeriana compounds: An in vivo and in vitro study on the guinea pig ileum. Archives of international pharmacodynamics, 1982, 257:274–278.

33. Krieglstein J, Grusla D. Zentraldämpfende Inhaltsstoffe im Baldrian. Valepotriate, Valerensäure, Valeranon und ätherisches Öl sind jedoch unwirksam. Deutsche Apotheker Zeitung, 1988, 128:2041–2046.

34. German Commission E Monograph, Valerianae radix. Bundesanzeiger, 1985, 90:15 May.

35. Tortarolo M et al. In vitro effects of epoxide-bearing valepotriates on mouse early hematopoietic progenitor cells and human T-lymphocytes. Archives of toxicology, 1982, 51:37–42.

36. Braun R. Valepotriates with an epoxide structure-oxygenating alkylating agents. Planta medica, 1982, 41:21–28.

37. Tufik S. Effects of a prolonged administration of valepotriates in rats on the mothers and their offspring. Journal of ethnopharmacology, 1985, 87:39–44.

38. Willey LB et al. Valerian overdose: a case report. Veterinary and human toxicology, 1995, 37:364–365.

39. MacGregor FB. Hepatotoxicity of herbal remedies. British medical journal, 1989, 299:1156–1157.

 

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