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WHO Monographs on Selected Medicinal Plants - Volume 2
(2004; 358 pages) View the PDF document
Table of Contents
View the documentIntroduction
View the documentGeneral technical notices
View the documentRadix Althaeae
View the documentHerba Andrographidis
View the documentRadix Angelicae Sinensis
View the documentFlos Calendulae
View the documentFlos Caryophylli
View the documentRhizoma Cimicifugae Racemosae
View the documentFolium cum Flore Crataegi
View the documentRadix Eleutherococci
View the documentAetheroleum Eucalypti
View the documentFolium Eucalypti
View the documentCortex Frangulae
View the documentFolium et Cortex Hamamelidis
View the documentSemen Hippocastani
View the documentHerba Hyperici
View the documentAetheroleum Melaleucae Alternifoliae
View the documentFolium Melissae
View the documentAetheroleum Menthae Piperitae
View the documentFolium Menthae Piperitae
View the documentFolium Ocimi Sancti
View the documentOleum Oenotherae Biennis
View the documentRhizoma Piperis Methystici
View the documentCortex Pruni Africanae
View the documentCortex Rhamni Purshianae
View the documentFlos Sambuci
View the documentRadix Senegae
View the documentFructus Serenoae Repentis
View the documentFructus Silybi Mariae
View the documentHerba Tanaceti Parthenii
View the documentRadix Urticae
View the documentFolium Uvae Ursi
View the documentAnnex: Participants in the Second WHO Consultation on Selected Medicinal Plants
 

Folium Eucalypti

Definition

Folium Eucalypti consists of the dried leaves of Eucalyptus globulus Labill (Myrtaceae) (1-3).

Synonyms

Eucalyptus cordata Miq., E. diversifolia Miq., E. gigantea Dehnh., E. glauca D.C., E. globulus St Lag., E. pulverulenta Link (4).

Selected vernacular names

Alcanfor, arbre à la fièvre, Australian fever tree, bach dan xanh, Blaugummibaum, bluegum tree, calibtus, calipso, daun ekaliptus, eucalipus, eucalypto, eucalyptus, Eucalyptusblätter, feuilles d’eucalyptus, fevertree, Fieberbaum, Fieberhilbaum, gigante, gommier bleu, gommier bleu de Tasmania, gum tree, iron bark tree, kalatus, kaphur, khuynh diep, mtiulaya, nkwu-ishi, oykaliptus, Tasmanian bluegum, yukari (1, 4-8).

Geographical distribution

Indigenous to Australia, cultivated in subtropical regions of the world including Africa, South America (e.g. Argentina, Brazil and Paraguay), Asia (e.g. China, India and Indonesia), southern Europe and the United States of America (1, 4, 6, 8-10).

Description

A large tree with smooth bark, very pale or ash-grey, up to 3-20 m high. Branchlets quadrangular, glaucous. Leaves of young trees and first leaves of young shoots opposite, sessile, oval-oblong, with a cordate base, farinaceousglaucous; older leaves dangling, spirally arranged, lanceolate-falcate, up to 30 cm long. Flowers with very short pedicels, mostly umbellate, sometimes 2-3 in a fascicle. Calyx tube double: outer tube drops early, smooth; inner tube semipersistent and warty. Stamens about 1.5cm long. Fruit turbinate, angular, 2.0-2.5 cm in diameter (11, 12).

Plant material of interest: dried leaves

General appearance

Leaf lanceolate-falcate, bifacial, 8-30 cm long, 2-7 cm wide; petiole twisted, strongly wrinkled, 2-3 cm, occasionally 5 cm, in length; apex, when present, acute or acuminate; base unequal, obtuse or somewhat rounded, margin uneven, revolute; ventral and dorsal surfaces greyish-green to pale yellowishgreen, coriaceous, glaucous, glabrous, glandular-punctate, with numerous small, rounded, brown dots of cork; venation pinnate-reticulate, veins of the first order running to a short distance from margin where they are anastomosed and form a vein nearly parallel with the margin (1-3, 8).

Organoleptic properties

Odour: aromatic, camphoric; taste: aromatic, pungent, bitter (1, 3, 8).

Microscopic characteristics

Upper and lower epidermis composed of clear, polygonal cells with thick cutinized outer walls; both layers possess sunken stomata. Chlorenchyma differentiated into 2 palisade regions: both regions composed of 3-4 (usually 4) rows of cells which face each epidermis; in each region large, subglobular internal glands occur, lined with secretory epithelium and containing yellow oil. Parenchyma spongy, a narrow zone of loosely arranged cells between the 2 palisade regions; its cells contain rosette aggregates or monoclinic prisms of calcium oxalate crystals. Fibrovascular bundles throughout the spongy parenchyma; in midrib and petiole, interrupted arc of slightly lignified pericyclic fibres occurs just outside these bundles (8).

Powdered plant material

Greyish-green; fragments of chlorenchyma with numerous embedded, broken, yellow, schizogenous oil glands; calcium oxalate crystals in rosette aggregates or monoclinic prisms; fragments of epidermis with polygonal cells having very thick cuticle, numerous anomocytic stomata of more than 80 µm in diameter, fragments of sclerenchyma fibres; fragments of cork, tracheids, vessels and fibres (1, 3, 8).

General identity tests

Macroscopic and microscopic examinations, microchemical analysis and thin-layer chromatography for 1,8-cineole (1-3, 8, 13).

Purity tests

Microbiological

Tests for specific microorganisms and microbial contamination limits are as described in the WHO guidelines on quality control methods for medicinal plants (14).

Foreign organic matter

Not more than 1% fruits, and not more than 2% stems and other foreign matter (1-3).

Total ash

Not more than 6% (2, 3).

Acid-insoluble ash

Not more than 0.2% (8).

Loss on drying

Not more than 10% (3).

Pesticide residues

The recommended maximum limit of aldrin and dieldrin is not more than 0.05mg/kg (15). For other pesticides, see the European pharmacopoeia (15), and the WHO guidelines on quality control methods for medicinal plants (14) and pesticide residues (16).

Heavy metals

For maximum limits and analysis of heavy metals, consult the WHO guidelines on quality control methods for medicinal plants (14).

Radioactive residues

Where applicable, consult the WHO guidelines on quality control methods for medicinal plants (14) for the analysis of radioactive isotopes.

Other purity tests

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

Chemical assays

Contains not less than 2% (v/w) essential oil, consisting of not less than 70% (w/w) 1,8-cineole (also known as cineol, cineole or eucalyptol) (1, 3). A thinlayer chromatography method is available for qualitative determination, using 1,8-cineole as a reference standard (3).

Major chemical constituents

Dried leaves contain 1-3% (v/w) essential oil (fresh leaves contain 0.4-1.6%), the major constituent of which is 1,8-cineole (54-95%). In addition, there are moderate amounts of other monoterpenes, including α-pinene (2.6%), p-cymene (2.7%), aromadendrene, cuminaldehyde, globulol and pinocarveol. Gas chromatography and gas chromatography-mass spectroscopy of the oil indicated the presence of more than 70 components, 48 of which were identified. The concentration of α-terpeneol was estimated to be 28% (17). The leaves are rich in tannins and ellagitannins, and also contain 2-4% triterpenes (ursolic acid derivatives), a series of phloroglucinol-sesquiterpene-coupled derivatives (macrocarpals B, C, D, E, H, I and J) and flavonoids (rutin, quercetin, quercitrin and hyperoside) (5, 7, 10, 12, 17-19). The structure of the major monoterpene, 1,8-cineole, is presented below.


1,8-cineole (eucalyptol)

Medicinal uses

Uses supported by clinical data

None.

Uses described in pharmacopoeias and in traditional systems of medicine

As an expectorant for symptomatic treatment of mild inflammation of the respiratory tract and bronchitis (20). Also for symptomatic treatment of asthma, fever and inflammation of the throat (1).

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

Treatment of cystitis, diabetes, gastritis, kidney disease (unspecified), laryngitis, leukorrhoea, malaria, pimples, ringworm, wounds, ulcers of the skin, urethritis and vaginitis (5).

Pharmacology

Experimental pharmacology

Antibacterial and antifungal activity

An ethanol-water extract of Folium Eucalypti inhibited the growth in vitro of Staphylococcus aureus at a concentration of 25 µg/ml (21). An aqueous leaf extract inhibited the growth in vitro of Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Enterococcus faecalis (MIC 0.07-1.30mg/ml) (22). A methanol extract of the leaves inhibited the growth in vitro of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans (MIC 1.25-10.00mg/ml) (23). A fluidextract of the leaves inhibited the growth in vitro of Mycobacterium tuberculosis (MIC 6.25mg/ml) (24). A methanol-water extract of the leaves inhibited the growth in vitro of Candida albicans (25).

Antiviral activity

An aqueous leaf extract inhibited the replication of influenza virus A2 (Mannheim 57), vaccinia virus and herpes simplex virus type 2 in vitro at a concentration of 0.1% (26).

Antimalarial activity

Intragastric administration of a hexane leaf extract to mice (100 mg/kg body weight) did not inhibit the growth of Plasmodium berghei (27). Furthermore, administration of an aqueous (3.48 g/kg body weight) or chloroform (264 mg/kg body weight) leaf extract to chickens by gastric lavage did not inhibit the growth of P. gallinaceum (28). An ethanol-water extract of the leaves inhibited the growth in vitro of P. falciparum at a concentration of 75 µg/ml (21).

Antidiabetes activity

A hot aqueous extract of the leaves suppressed streptozocin-induced hyperglycaemia in mice when added to the diet (6.25%) and drinking-water (0.25%). The same extract did not stimulate insulin production by the pancreas (29). However, intragastric administration of aqueous or ethanol extracts of the leaves at a dose of 1 g/kg body weight did not suppress alloxan-induced hyperglycaemia in mice and rabbits (30, 31).

Clinical pharmacology

None.

Contraindications

Preparations of Folium Eucalypti should not be administered internally to children or patients with inflammation of the gastrointestinal tract, gall bladder disease or impaired liver function (4, 20).

Warnings

Folium Eucalypti preparations should not be applied to the face, especially the nose, of infants or young children (20). Keep out of reach of children.

Precautions

Drug interactions

Although no published drug interactions were found, a number of animal studies indicate possible concern that the leaf essential oil may induce liver enzymes involved in drug metabolism. Therefore, the effects of other drugs may be decreased following concomitant administration (20, 32).

Carcinogenesis, mutagenesis, impairment of fertility

A tincture of the leaves was not mutagenic in the Salmonella/microsome assay using S. typhimurium strains TA100 and TA98 (33).

Pregnancy: teratogenic effects

The leaf essential oil was not teratogenic when administered subcutaneously to pregnant mice (135mg/kg body weight) daily on days 6-15 of gestation (34).

Pregnancy: non-teratogenic effects

Eucalyptol (500 mg/kg body weight, administered subcutaneously) has been reported to penetrate the placenta in rodents, and reach concentrations in the fetal blood which are sufficient to stimulate hepatic enzyme activity (35). Therefore, Folium Eucalypti should not be administered during pregnancy without medical supervision.

Paediatric use

See Contraindications and Warnings.

Other precautions

No information available on general precautions or precautions concerning drug and laboratory test interactions or nursing mothers. Therefore, Folium Eucalypti should not be used during lactation without medical supervision.

Adverse reactions

Excessive ingestion of Folium Eucalypti can cause nausea, vomiting and diarrhoea (20). Several cases of urticaria, contact dermatitis and skin irritation have been reported after therapeutic doses (36).

Dosage forms

Crude drug (1, 20). Store in a tightly closed container, protected from light (3).

Posology

(Unless otherwise indicated)
Daily dosage: 4-6g crude drug or equivalent preparations. Infusion: pour 150 ml of hot water over a half teaspoon of the leaves, allow them to stand for 10 minutes, then remove the leaves with a strainer (10, 20). One cup (240 ml) of the freshly prepared infusion is drunk slowly three times daily. The vapour of the hot infusion is inhaled deeply (10).

References

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

2. British herbal pharmacopoeia. London, British Herbal Medicine Association, 1996.

3. European pharmacopoeia, 3rd ed., Suppl. 2000. Strasbourg, Council of Europe, 1999.

4. Blaschek W et al., eds. Hagers Handbuch der pharmazeutischen Praxis. Folgeband 2: Drogen A-K, 5th ed. Berlin, Springer-Verlag, 1998.

5. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, February 14, 1998 production (an online database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network [STN] of Chemical Abstracts Services).

6. Iwu MM. Handbook of African medicinal plants. Boca Raton, FL, CRC Press, 1993.

7. Newall CA, Anderson LA, Phillipson JD. Herbal medicines, a guide for health-care professionals. London, The Pharmaceutical Press, 1996.

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

9. Heyne K. De nuttige planten van Indonesie, 3rd ed. Wageningen, H. Veenman & Konen, 1950.

10. Bisset NG. Herbal drugs and phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994.

11. Backer CA, van den Brink B. Flora of Java. Vol. 2. Groningen, Netherlands, NVP Noordhof, 1965.

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

13. Wagner H, Bladt S. Plant drug analysis, 2nd ed. Berlin, Springer-Verlag, 1996.

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

15. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1996.

16. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (document WHO/FSF/FOS/97.7).

17. Zhao ZD et al. Gas chromatography of residue from fractional distillation of Eucalyptus globulus leaf oil. Linchan Huaxue Yu Gongye, 1997, 17:37-40.

18. Nishizawa M et al. Macrocarpals: HIV-RTase inhibitors of Eucalyptus globulus. Tetrahedron Letters, 1992, 33:2983-2986.

19. Osawa K et al. Macrocarpals H, I, and J from the leaves of Eucalyptus globulus. Journal of Natural Products, 1996, 59:823-827.

20. Blumenthal M et al., eds. The complete German Commission E monographs. Austin, TX, American Botanical Council, 1998.

21. Aswal BS et al. Screening of Indian plants for biological activity. Part X. Indian Journal of Experimental Biology, 1984, 22:312-322.

22. Brantner A, Grein E. Antibacterial activity of plant extracts used externally in traditional medicine. Journal of Ethnopharmacology, 1994, 44:35-40.

23. Navarro V et al. Antimicrobial evaluation of some plants used in Mexican traditional medicine for the treatment of infectious diseases. Journal of Ethnopharmacology, 1996, 53:143-147.

24. Fitzpatrick FK. Plant substances active against Mycobacterium tuberculosis. Antibiotics and Chemotherapy, 1954, 4:528.

25. Cacerea A et al. Plants used in Guatemala for the treatment of dermatophytic infections. Screening for antimycotic activity of 44 plant extracts. Journal of Ethnopharmacology, 1991, 31:263-276.

26. May G, Willuhn G. Antiviral activity of aqueous extracts from medicinal plants in tissue cultures. Arzneimittel-Forschung, 1978, 28:1-7.

27. Brandao M et al. Antimalarial experimental chemotherapy using natural products. Ciência e Cultura Sociedad Brasileira para o Progresso da Ciência, 1985, 37:1152-1163.

28. Spencer CF et al. Survey of plants for antimalarial activity. Lloydia, 1947, 10:145-174.

29. Swanson-Flatt SK et al. Traditional plant treatments for diabetes. Studies in normal and streptozotocin-diabetic mice. Diabetologia, 1990, 33:462-464.

30. Lin YC et al. Studies on the hypoglycemic activity of the medical herbs. Formosan Medical Association, 1964, 63:400-404.

31. Perez RM et al. A study of the hypoglycemic effect of some Mexican plants. Journal of Ethnopharmacology, 1984, 12:253-262.

32. Corrigan D. Eucalyptus species. In: DeSmet PAGM et al., eds. Adverse reactions of herbal drugs. Berlin, Springer-Verlag, 1992:125-133.

33. Schimmer O et al. An evaluation of 55 commercial plant extracts in the Ames mutagenicity test. Pharmazie, 1994, 49:448-451.

34. Pages N et al. The essential oils and their potential teratogenic properties: example of the essential oils of Eucalyptus globulus preliminary study with mice. Plantes médicinales et Phytotherapie, 1990, 24:21-26.

35. Jori A, Briatico G. Effects of eucalyptol on microsomal enzyme activity of foetal and newborn rats. Biochemical Pharmacology, 1973, 22:543-544.

36. Mitchell J, Rook J. Botanical dermatology. Vancouver, Greengrass, 1979:484-486.

 

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