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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
 

Herba Thymi

Definition

Herba Thymi is the dried leaves and flowering tops of Thymus vulgaris L. or of Thymus zygis L. (Lamiaceae) (1, 2).

Synonyms

Lamiaceae are also known as Labiatae.

Selected vernacular names

Common thyme, farigola, garden thyme, herba timi, herba thymi, mother of thyme, red thyme, rubbed thyme, ten, thick leaf thyme, thym, Thymian, thyme, time, timi, tomillo, za'ater (1, 3–7).

Description

An aromatic perennial sub-shrub, 20–30 cm in height, with ascending, quadrangular, greyish brown to purplish brown lignified and twisted stems bearing oblong-lanceolate to ovate-lanceolate greyish green leaves that are pubescent on the lower surface. The flowers have a pubescent calyx and a bilobate, pinkish or whitish, corolla and are borne in verticillasters. The fruit consists of 4 brown ovoid nutlets (5, 8, 9).

Plant material of interest: dried leaves and flowering tops

General appearance

Thymus vulgaris

Leaf 4–12 mm long and up to 3mm wide; it is sessile or has a very short petiole. The lamina is tough, entire, lanceolate to ovate, covered on both surfaces by a grey to greenish grey indumentum; the edges are markedly rolled up towards the abaxial surface. The midrib is depressed on the adaxial surface and is very prominent on the abaxial surface. The calyx is green, often with violet spots, and is tubular; at the end are 2 lips of which the upper is bent back and has 3 lobes on its end; the lower is longer and has 2 hairy teeth. After flowering, the calyx tube is closed by a crown of long, stiff hairs. The corolla, about twice as long as the calyx, is usually brownish in the dry state and is slightly bilabiate (1).

Thymus zygis

Leaf 1.7–6.5 mm long and 0.4–1.2 mm wide; it is acicular to linear-lanceolate and the edges are markedly rolled toward the abaxial surface. Both surfaces of the lamina are green to greenish grey and the midrib is sometimes violet; the edges, in particular at the base, have long, white hairs. The dried flowers are very similar to those of Thymus vulgaris (1).

Organoleptic properties

Odour and taste aromatic (1–3, 5).

Microscopic characteristics

In leaf upper epidermis, cells tangentially elongated in transverse section with a thick cuticle and few stomata, somewhat polygonal in surface section with beaded vertical walls and striated cuticle, the stoma being at a right angle to the 2 parallel neighbouring cells. Numerous unicellular, non-glandular hairs up to 30µm in length with papillose wall and apical cell, straight, or pointed, curved, or hooked. Numerous glandular hairs of two kinds, one with a short stalk embedded in the epidermal layer and a unicellular head, the other with an 8- to 12-celled head and no stalk. Palisade parenchyma of 2 layers of columnar cells containing many chloroplastids; occasionally an interrupted third layer is present. Spongy parenchyma of about 6 layers of irregular-shaped chlorenchyma cells and intercellular air-spaces (5).

Powdered plant material

Grey-green to greenish brown powder; leaf fragments, epidermal cells prolonged into unicellular pointed, papillose trichomes, 60µm long; trichomes of the lower surface uniseriate, 2–3 celled, sharp pointed, up to 300µm in diameter, numerous labiate trichomes with 8–12 secretory cells up to 80µm in diameter; broadly elliptical caryophyllaceous stomata. Six- to 8-celled uniseriate trichomes from the calyx up to 400µm long; pollen grains spherical; pericyclic fibres of the stem (1–3).

Geographical distribution

Indigenous to southern Europe. It is a pan-European species that is cultivated in Europe, the United States of America and other parts of the world (2, 3, 5, 10).

General identity tests

Macroscopic and microscopic examinations (1, 5), and chemical and thinlayer chromatography tests for the characteristic volatile oil constituent, thymol [1].

Purity tests

Microbiology

The test for Salmonella spp. in Herba Thymi products should be negative. The maximum acceptable limits of other microorganisms are as follows (11–13). For preparation of infusion: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g. Preparations for oral use: aerobic bacteria-not more than 105/ml; fungi-not more than 104/ml; enterobacteria and certain Gram-negative bacteria-not more than 103/ml; Escherichia coli-0/ml.

Foreign organic matter

Not more than 10% of stem having a diameter up to 1mm. Leaves with long trichomes at their base and with weakly pubescent other parts not allowed (1). The leaves and flowering tops of Origanum creticum or O. dictamnus are considered adulterants (3, 5). Other foreign organic matter, not more than 2% (2).

Total ash

Not more than 15% (1).

Acid-insoluble ash

Not more than 2.0% (1).

Moisture

Not more than 10% (1).

Pesticide residues

To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin in Herba Thymi is not more than 0.05 mg/kg (13). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (11) and guidelines for predicting dietary intake of pesticide residues (14).

Heavy metals

Recommended lead and cadmium levels are not more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (11).

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 (11).

Other purity tests

Chemical, alcohol-soluble extractive, and water-soluble extractive tests to be established in accordance with national requirements.

Chemical assays

Herba Thymi contains not less than 1.0% volatile oil (2, 3), and not less than 0.5% phenols. Volatile oil is quantitatively determined by water/steam distillation (1), and the percentage content of phenols expressed as thymol is determined by spectrophotometric analysis (1). Thin-layer chromatographic analysis is used for thymol, carvacrol, and linalool (1, 15).

Major chemical constituents

Herba Thymi contains about 2.5% but not less than 1.0% of volatile oil. The composition of the volatile oil fluctuates depending on the chemotype under consideration. The principal components of Herba Thymi are thymol [1] and carvacrol [2] (up to 64% of oil), along with linalool, p-cymol, cymene, thymene, α-pinene, apigenin, luteolin, and 6-hydroxyluteolin glycosides, as well as di-, tri- and tetramethoxylated flavones, all substituted in the 6- position (for example 5,4'-dihydroxy-6,7-dimethoxyflavone, 5,4'-dihydroxy- 6,7,3'-trimethoxyflavone and its 8-methoxylated derivative 5,6,4'-trihydroxy- 7,8,3'-trimethoxyflavone) (1, 36, 9).

Dosage forms

Dried herb for infusion, extract, and tincture (1).

Medicinal uses

Uses supported by clinical data

None.

Uses described in pharmacopoeias and in traditional systems of medicine

Thyme extract has been used orally to treat dyspepsia and other gastrointestinal disturbances; coughs due to colds, bronchitis and pertussis; and laryngitis and tonsillitis (as a gargle). Topical applications of thyme extract have been used in the treatment of minor wounds, the common cold, disorders of the oral cavity, and as an antibacterial agent in oral hygiene (3, 5, 8, 15, 16). Both the essential oil and thymol are ingredients of a number of proprietary drugs including antiseptic and healing ointments, syrups for the treatment of respiratory disorders, and preparations for inhalation. Another species in the genus, T. serpyllum L., is used for the same indications (8).

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

As an emmenagogue, sedative, antiseptic, antipyretic, to control menstruation and cramps, and in the treatment of dermatitis (7).

Pharmacology

Experimental pharmacology

Spasmolytic and antitussive activities

The spasmolytic and antitussive activity of thyme has been most often attributed to the phenolic constituents thymol and carvacrol, which make up a large percentage of the volatile oil (17). Although these compounds have been shown to prevent contractions induced in the ileum and the trachea of the guinea-pig, by histamine, acetylcholine and other reagents, the concentration of phenolics in aqueous preparations of the drug is insufficient to account for this activity (18, 19). Experimental evidence suggests that the in vitro spasmolytic activity of thyme preparations is due to the presence of polymethoxyflavones (10). In vitro studies have shown that flavones and thyme extracts inhibit responses to agonists of specific receptors such as acetylcholine, histamine and L-norepinephrine, as well as agents whose actions do not require specific receptors, such as barium chloride (10). The flavones of thyme were found to act as noncompetitive and non-specific antagonists (10); they were also shown to be Ca2+ antagonists and musculotropic agents that act directly on smooth muscle (10).

Expectorant and secretomotor activities

Experimental evidence suggests that thyme oil has secretomotoric activity (20). This activity has been associated with a saponin extract from T. vulgaris (21). Stimulation of ciliary movements in the pharynx mucosa of frogs treated with diluted solutions of thyme oil, thymol or carvacrol has also been reported (22). Furthermore, an increase in mucus secretion of the bronchi after treatment with thyme extracts has been observed (23).

Antifungal and antibacterial activities

In vitro studies have shown that both thyme essential oil and thymol have antifungal activity against a number of fungi, including Cryptococcus neoformans, Aspergillus, Saprolegnia, and Zygorhynchus species (24–27). Both the essential oil and thymol had antibacterial activity against Salmonella typhimurium, Staphylococcus aureus, Escherichia coli, and a number of other bacterial species (28, 29). As an antibiotic, thymol is 25 times as effective as phenol, but less toxic (30).

Contraindications

Pregnancy and lactation (See Precautions, below).

Warnings

No information available.

Precautions

General

Patients with a known sensitivity to plants in the Lamiaceae (Labiatae) should contact their physician before using thyme preparations. Patients sensitive to birch pollen or celery may have a cross-sensitivity to thyme (31).

Carcinogenesis, mutagenesis, impairment of fertility

Thyme essential oil did not have any mutagenic activity in the Bacillus subtilis rec-assay or the Salmonella/microsome reversion assay (32, 33). Recent investigations suggest that thyme extracts are antimutagenic (34) and that luteolin, a constituent of thyme, is a strong antimutagen against the dietary carcinogen Trp-P-2 (35).

Pregnancy: non-teratogenic effects

The safety of Herba Thymi preparations during pregnancy or lactation has not been established. As a precautionary measure, the drug should not be used during pregnancy or lactation except on medical advice. However, widespread use of Herba Thymi has not resulted in any safety concerns.

Nursing mothers

See Pregnancy: non-teratogenic effects, above.

Other precautions

No information available concerning drug interactions, drug and laboratory test interactions, paediatric use, or teratogenic effects on pregnancy.

Adverse reactions

Contact dermatitis has been reported. Patients sensitive to birch pollen or celery may have a cross-sensitivity to thyme (31).

Posology

Adults and children from 1 year: 1–2g of the dried herb or the equivalent amount of fresh herb as an oral infusion several times a day (30, 36); children up to 1 year: 0.5–1g (36). Fluid extract: dosage calculated according to the dosage of the herb (37). Tincture (1: 10, 70% ethanol): 40 drops up to 3 times daily (38). Topical use: a 5% infusion as a gargle or mouth-wash (30, 38).

References

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

2. Materia medika Indonesia, Jilid. Jakarta, IV Departemen Kesehatan, Republik Indonesia, 1980.

3. British herbal phamacopoeia, Part 2. London, British Herbal Medicine Association, 1979.

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

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

6. Ghazanfar SA. Handbook of Arabian medicinal plants. Boca Raton, FL, CRC Press, 1994:128.

7. 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).

8. Bruneton J. Pharmacognosy, phytochemistry, medicinal plants. Paris, Lavoisier, 1995.

9. Mossa JS, Al-Yahya MA, Al-Meshal IA. Medicinal plants of Saudi Arabia, Vol. 1. Riyadh, Saudi Arabia, King Saud University Libraries, 1987.

10. Van den Broucke CO, Lemli JA. Spasmolytic activity of the flavonoids from Thymus vulgaris. Pharmaceutisch Weekblad, scientific edition, 1983, 5:9–14.

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

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

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

14. 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).

15. Twetman S, Hallgren A, Petersson LG. Effect of antibacterial varnish on mutans Streptococci in plaque from enamel adjacent to orthodontic appliances. Caries research, 1995, 29:188–191.

16. Petersson LG, Edwardsson S, Arends J. Antimicrobial effect of a dental varnish, in vitro. Swedish dental journal, 1992, 16:183–189.

17. Reiter M, Brandt W. Relaxant effects on tracheal and ileal smooth muscles of the guinea pig. Arzneimittel-Forschung, 1985, 35:408–414.

18. Van Den Broucke CO. Chemical and pharmacological investigation on Thymi herba and its liquid extracts. Planta medica, 1980, 39:253–254.

19. Van Den Broucke CO, Lemli JA. Pharmacological and chemical investigation of thyme liquid extracts. Planta medica, 1981, 41:129–135.

20. Gordonoff T, Merz H. Über den Nachweis der Wirkung der Expektorantien. Klinische Wochenschrift, 1931, 10:928–932.

21. Vollmer H. Untersuchungen über Expektorantien und den Mechanismus ihrer Wirkung. Klinische Wochenschrift, 1932, 11:590–595.

22. Freytag A. Über den Einfluß von Thymianöl, Thymol und Carvacrol auf die Flimmerbewegung. Pflügers Archiv, European journal of physiology, 1933, 232:346– 350.

23. Schilf F. Einfluss von Azetylcholin, Adrenalin, Histamin und Thymianextrakt auf die Bronchialschleimhautsekretion; zugleich ein Beitrag zur Messung der Bronchialschleimhautsekretion. Naunyn-Schmiedebergs Archiv für Pharmakologie, 1932, 166:22–25.

24. Vollon C, Chaumont JP. Antifungal properties of essential oils and their main components upon Cryptococcus neoformans. Mycopathology, 1994, 128:151– 153.

25. Perrucci S et al. In vitro antimycotic activity of some natural products against Saprolegnia ferax. Phytotherapy research, 1995, 9:147–149.

26. Pasteur N et al. Antifungal activity of oregano and thyme essential oils applied as fumigants against fungi attacking stored grain. Journal of food protection, 1995, 58:81– 85.

27. Tantaouielaraki A, Errifi A. Antifungal activity of essential oils when associated with sodium chloride or fatty acids. Grasas-y-aceites, 1994, 45:363–369.

28. Janssen AM, Scheffer JJC, Baerheim-Svendsen A. Antimicrobial activity of essential oils: A 1976–1986 literature review. Aspects of the test methods. Planta medica, 1987, 53:395–398.

29. Juven BJ, Kanner J, Schved F, Weisslowicz H. Factors that interact with the antibacterial action of thyme essential oil and its active constituents. Journal of applied bacteriology, 1994, 76:626–631.

30. Czygan C-F. Thymian, Thymi Herba. In: Wichtl M. ed. Teedrogen, 2nd ed. Stuttgart, Wissenschaftliche Verlagsgesellschaft, 1989:498–500.

31. Wüthrich B, Stäger P, Johannson SGO. Rast-specific IGE against spices in patients sensitized against birch pollen, mugwort pollen and celery. Allergologie, 1992, 15:380–383.

32. Zani F et al. Studies on the genotoxic properties of essential oils with Bacillus subtilis rec-assay and Salmonella/microsome reversion assay. Planta medica, 1991, 57:237– 241.

33. Azizan A, Blevins RD. Mutagenicity and antimutagenicity testing of six chemicals associated with the pungent properties of specific spices as revealed by the Ames Salmonella microsomal assay. Archives of environmental contamination and toxicology, 1995, 28:248–258.

34. Natake M et al. Herb water-extracts markedly suppress the mutagenicity of Trp-P- 2. Agricultural and biological chemistry, 1989, 53:1423–1425.

35. Samejima K et al. Luteolin, a strong antimutagen against dietary carcinogen, Trp-P- 2, in peppermint, sage, and thyme. Journal of agricultural and food chemistry, 1995, 43:410–414.

36. Dorsch W et al. In: Empfehlungen zu Kinderdosierungen von monographierten Arzneidrogen und ihren Zubereitungen. Bonn, Kooperation Phytopharmaka, 1993:100– 101.

37. Hochsinger K. Die Therapie des Krampf- und Reizhustens. Wiener Medizinische Wochenschrift, 1931, 13:447–448.

38. Van Hellemont J. Fytotherapeutisch compendium, 2nd ed. Bonn, Scheltema & Holkema, 1988:599–605.

 

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