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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
 

Aloe

Definition

Aloe is the dried juice of the leaves of Aloe vera (L.) Burm. f. or of A. ferox Mill. and its hybrids with A. africana Mill. and A. spicata Baker (Liliaceae) (1–6).

Synonyms

Aloe vera (L.) Burm. f.

Aloe barbadensis Mill., Aloe chinensis Bak., A. elongata Murray, A. indica Royle, A. officinalis Forsk., A. perfoliata L., A. rubescens DC, A. vera L. var. littoralis König ex Bak., A. vera L. var. chinensis Berger, A. vulgaris Lam. (7).

In most formularies and reference books, Aloe barbadensis Mill. is regarded as the correct species name, and Aloe vera (L.) Burm. f. is considered a synonym. However, according to the International Rules of Botanical Nomenclature, Aloe vera (L.) Burm. f. is the legitimate name for this species (810). The genus Aloe has also been placed taxonomically in a family called Aloeaceae.

Aloe ferox Mill.

Aloe horrida Haw., A. perfoliata Thunberg., A. pseudoferox Salm. Dyck, A. socotrina Masson., A. supralaevis Haw., Pachydendron ferox Humb. & Bonpl., P. supralaeve Haw. (7).

Selected vernacular names

Aloe capensis, aloe curacao, aloe vera, aloes, aloès, aloès du Cape, aloès fèroce, aloes vrai, aloès vulgaire, alovis, Barbadoes aloe, Barbadoes aloes, Barbados aloe, Bergaalwyn, Bitteraalwyn, Cape aloe, chirukattali, Curacao aloe, Curacao aloes, Curacao alos, Echte Aloe, ghai kunwar, ghai kunwrar, gheekuar, ghikanvar, ghikuar, ghikumar, ghikumari, ghikwar, ghiu kumari, ghrita kumari, ghritakumari, grahakanya, gwar-patha, haang takhe, hlaba, Indian aloe, jadam, korphad, kumari, kumaro, kunvar pata, kunwar, laloi, laluwe, lo-hoei, lo-hoi, lou-houey, lu wei, luchuy, manjikattali, Mediterranean aloe, murr sbarr, musabar, rokai, sabbara, saber, sábila, sabilla, sabr, saibr, savila, savilla, semper vivum, shubiri, sibr, siang-tan, star cactus, tuna, umhlaba, waan haang charakhe, wan-hangchorakhe, yaa dam, yadam, zábila, zambila (1, 7, 11).

Description

Aloe vera (L.) Burm. f.

Succulent, almost sessile perennial herb; leaves 30–50cm long and 10cm broad at the base; colour pea-green (when young spotted with white); bright yellow tubular flowers 25–35cm in length arranged in a slender loose spike; stamens frequently project beyond the perianth tube (12).

Aloe ferox Mill.

Arborescent perennial shrub with a single stem of 2–3m in height, crowned by a large rosette of numerous leaves which are glaucous, oval-lanceolate, 40– 60cm in length, thorny on the ridge and the edges; inflorescence an erect raceme 60 cm in height; flowers with perianth 2.5 cm in length, red, yellow, or orange (2).

Plant material of interest: dried juice

Solidified juice originating in the cells of the pericycle and adjacent leaf parenchyma, and flowing spontaneously from the cut leaf, allowed to dry with or without the aid of heat.

It is not to be confused with Aloe Vera Gel, which is the colourless mucilaginous gel obtained from the parenchymatous cells in the leaves of Aloe vera (L.) Burm. f. (13).

General appearance

Curacao or Barbados Aloe, derived from Aloe vera (L.) Burm. f.

The dried juice occurs in dark chocolate-brown usually opaque masses; fracture, dull waxy, uneven, and frequently conchoidal (2, 6).

Cape Aloe, derived from A. ferox Mill. and its hybrids with A. africana Mill. and A. spicata Baker

The dried juice occurs in dark brown or greenish brown glassy masses, often covered with a yellowish powder; in thin fragments it is transparent and exhibits a yellowish, reddish brown or greenish tinge; fracture, smooth, even, and glassy (2, 6).

Organoleptic properties

Aloe is marketed as opaque masses that range from reddish black to brownish black to dark brown in colour. Odour, characteristic and disagreeable; taste, somewhat sour, nauseating and very bitter (2, 7, 12).

Microscopic characteristics

See "Powdered plant material" below.

Powdered plant material

Powdered aloes are yellowish brown to dark reddish brown. Microscopically, Cape Aloe appears as transparent brown or greenish brown irregular and angular fragments; Curacao Aloe shows fragments with numerous minute acicular crystals embedded in an amorphous matrix (1–3, 12, 14).

Geographical distribution

Native to southern and eastern Africa, and subsequently introduced into northern Africa, the Arabian peninsula, China, Gibraltar, the Mediterranean countries, and the West Indies (15). It is commercially cultivated in Aruba, Bonaire, Haiti, India, South Africa, the United States of America, and Venezuela (2, 7, 12, 14, 15).

General identity tests

Macroscopic and microscopic examinations (1–3, 7, 12, 14); solvent solubility (hot alcohol, boiling water, and ether) determination (2, 4–6); chemical reactions (1–6, 8, 12–14); and thin-layer chromatographic analysis employing barbaloin as the reference standard (4–7).

Purity tests

Microbiology

The test for Salmonella spp. in aloe products should be negative. The maximum acceptable limits of other microorganisms are as follows (16–18). 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

Adulterants: Aloe in commerce may sometimes be adulterated with black catechu, pieces of iron, and stones. These can be detected by examining alcohol- soluble extracts under ultraviolet light which gives a deep brown colour with aloe and a black colour with catechu (14).

Total ash

Not more than 2% (3–5).

Water-soluble extracts

Not less than 50% (1, 2, 14).

Alcohol-insoluble extracts

Not more than 10% (1–3, 14).

Moisture

Not more than 10% for Cape Aloe (6), and not more than 12% for Curacao or Barbados Aloe (2–6, 14).

Pesticide residues

To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin for Aloe is not more than 0.05 mg/kg (18). For other pesticides, see the WHO guidelines on quality control methods for medicinal plants (16) and guidelines for predicting dietary intake of pesticide residues (19).

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 (16).

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 (16).

Other tests

Acid-insoluble ash and chemical tests to be established in accordance with national requirements.

Chemical assays

Thin-layer chromatography and microchemical analyses are employed for the qualitative analysis for the presence of anthracene glycosides (1–7, 12, 14). Quantitative analysis of total anthracene glycosides, calculated as barbaloin, is performed by spectrophotometry (4, 5).

Curacao or Barbados Aloe, derived from Aloe vera (L.) Burm. f.

Contains not less than 28% of hydroxyanthracene derivatives, expressed as barbaloin (4–6).

Cape Aloe, derived from A. ferox Miller and its hybrids with A. africana Mill. and A. spicata Baker

Contains not less than 18% of hydroxyanthracene derivatives, expressed as barbaloin (4, 5).

Major chemical constituents

Aloe contains as its major and active principles hydroxyanthrone derivatives, mainly of the aloe-emodin-anthrone 10-C-glucoside type. The major constituent is known as barbaloin (aloin) (15–40%) (8, 13). It also contains hydroxyaloin (about 3%). Barbaloin (=aloin) is in fact a mixture of aloin A (10S) [1] and B (10R) [2]. A. ferox also contains aloinoside A [3] and B [4]. Aloin A and B interconvert through the anthranol form as do aloinoside A and B (13).

Dosage forms

Powdered, dried juice and preparations thereof for oral use.

Medicinal uses

Uses supported by clinical data

Short-term treatment of occasional constipation (2, 12, 13, 15).

Uses described in pharmacopoeias and in traditional systems of medicine

None.

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

Treatment of seborrhoeic dermatitis, peptic ulcers, tuberculosis, and fungal infections, and for reduction of blood sugar (glucose) levels (11, 20).

Pharmacology

Experimental pharmacology

As shown for senna, Aloe's mechanism of action is twofold. It stimulates colonic motility, augmenting propulsion and accelerating colonic transit, which reduces fluid absorption from the faecal mass. It also increases paracellular permeability across the colonic mucosa probably owing to an inhibition of Na+, K+-adenosine triphosphatase or to an inhibition of chloride channels (8, 21, 22), which results in an increase in the water content in the large intestine (21).

Clinical pharmacology

The laxative effects of Aloe are due primarily to the 1, 8-dihydroxyanthracene glycosides, aloin A and B (formerly designated barbaloin) (23, 24). After oral administration aloin A and B, which are not absorbed in the upper intestine, are hydrolysed in the colon by intestinal bacteria and then reduced to the active metabolites (the main active metabolite is aloe-emodin-9-anthrone) (25, 26), which like senna acts as a stimulant and irritant to the gastrointestinal tract (27). The laxative effect of Aloe is not generally observed before 6 hours after oral administration, and sometimes not until 24 or more hours after.

Toxicity

The major symptoms of overdose are griping and severe diarrhoea with consequent losses of fluid and electrolytes. Treatment should be supportive with generous amounts of fluid. Electrolytes, particularly potassium, should be monitored in all recipients, especially in children and the elderly (28).

Contraindications

As with other stimulant laxatives, products containing Aloe should not be used in patients with intestinal obstruction or stenosis, atony, severe dehydration with electrolyte depletion, or chronic constipation (28). Aloe should not be administered to patients with inflammatory intestinal diseases, such as appendicitis, Crohn disease, ulcerative colitis, irritable bowel syndrome, or diverticulitis, or to children under 10 years of age. Aloe should not be used during pregnancy or lactation except under medical supervision after evaluating benefits and risks. Aloe is also contraindicated in patients with cramps, colic, haemorrhoids, nephritis, or any undiagnosed abdominal symptoms such as pain, nausea, or vomiting (28, 29).

Warnings

Aloe-containing products should be used only if no effect can be obtained through a change of diet or use of bulk-forming products. Stimulant laxative products should not be used when abdominal pain, nausea, or vomiting are present. Rectal bleeding or failure to have a bowel movement within 24 hours after use of a laxative may indicate a serious condition. Chronic use may cause dependence and need for increased dosages, disturbances of water and electrolyte balance (e.g. hypokalaemia), and an atonic colon with impaired function (28).

The use of stimulant laxatives for more than 2 weeks requires medical supervision.

Chronic abuse with diarrhoea and consequent fluid and electrolyte losses (mainly hypokalaemia) may cause albuminuria and haematuria, and may result in cardiac and neuromuscular dysfunction, the latter particularly in the case of concomitant use of cardiac glycosides (digoxin), diuretics, corticosteroids, or liquorice root (see Precautions below).

Precautions

General

Laxatives containing anthraquinone glycosides should not be used continuously for longer than 1–2 weeks, owing to the danger of electrolyte imbalance.

Drug interactions

Decreased intestinal transit time may reduce absorption of orally administered drugs (30).

Existing hypokalaemia resulting from long-term laxative abuse can potentiate the effects of cardiotonic glycosides (digitalis, strophanthus) and antiarrhythmic drugs such as quinidine (30). The induction of hypokalaemia by drugs such as thiazide diuretics, adrenocorticosteroids, and liquorice root may be enhanced, and electrolyte imbalance may be aggravated (31).

Drug and laboratory test interactions

Standard methods may not detect anthranoid metabolites, so measurements of faecal excretion may not be reliable (26).

Urinary excretion of certain anthranoid metabolites may discolour the urine, which is not clinically relevant but which may cause false positive results for urinary urobilinogen, and for estrogens when measured by the Kober procedure (30).

Carcinogenesis, mutagenesis, impairment of fertility

Data on the carcinogenicity of Aloe are not available. While chronic abuse of anthranoid-containing laxatives was hypothesized to play a role in colorectal cancer, no causal relationship between anthranoid laxative abuse and colorectal cancer has been demonstrated (32–35).

In vitro (gene mutation and chromosome aberration tests) and in vivo (micronucleus test in murine bone marrow) genotoxicity studies, as well as human and animal pharmacokinetic data, indicate no genotoxic risk from Cape Aloe (36–38).

Pregnancy: teratogenic effects

No teratogenic or fetotoxic effects were seen in rats after oral treatment with aloe extract (up to 1000 mg/kg) or aloin A (up to 200 mg/kg) (39).

Pregnancy: non-teratogenic effects

Aloe should not be used during pregnancy except under medical supervision after benefits and risks have been evaluated (40).

Nursing mothers

Anthranoid metabolites appear in breast milk. Aloe should not be used during lactation except under medical supervision, as there are insufficient data available to assess the potential for pharmacological effects in the breast-fed infant (30, 40).

Paediatric use

Oral use of Aloe in children under 10 years old is contraindicated.

Adverse reactions

Abdominal spasms and pain may occur after even a single dose. Overdose can lead to colicky abdominal spasms and pain, as well as the formation of thin, watery stools (28).

Chronic abuse of anthraquinone stimulant laxatives can lead to hepatitis (41). Long-term laxative abuse may lead to electrolyte disturbances (hypokalaemia, hypocalcaemia), metabolic acidosis, malabsorption, weight loss, albuminuria, and haematuria (30, 42, 43). Weakness and orthostatic hypotension may be exacerbated in elderly patients when stimulant laxatives are repeatedly used (31). Secondary aldosteronism may occur owing to renal tubular damage after aggravated use. Steatorrhoea and protein-losing gastroenteropathy with hypoalbuminaemia have also been observed, as have excessive excretion of calcium in the stools and osteomalacia of the vertebral column (44, 45). Melanotic pigmentation of the colonic mucosa (pseudomelanosis coli) has been observed in individuals taking anthraquinone laxatives for extended time periods (29, 42). The pigmentation is clinically harmless and usually reversible within 4 to 12 months after the drug is discontinued (29, 42). Conflicting data exist on other toxic effects such as intestinal-neuronal damage after long-term use (42, 46).

Posology

The correct individual dose is the smallest amount required to produce a soft-formed stool (26). As a laxative for adults and children over 10 years old, 0.04–0.11 g (Curacao or Barbados Aloe) or 0.06–0.17 g (Cape Aloe) of the dried juice (6, 14), corresponding to 10–30mg hydroxyanthraquinones per day, or 0.1 g as a single dose in the evening.

References

1. The United States pharmacopeia XXIII. Rockville, MD, US Pharmacopeial Convention, 1996.

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

3. The Japanese pharmacopoeia XIII. Tokyo, The Society of Japanese Pharmacopoeia, 1996.

4. Pharmacopée française. Paris, Adrapharm, 1996.

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

6. British pharmacopoeia. London, Her Majesty's Stationery Office, 1993.

7. Hänsel R et al., eds. Hagers Handbuch der Pharmazeutischen Praxis, Vol. 6, 5th ed. Berlin, Springer, 1994.

8. Bradley PR, ed. British herbal compendium, Vol. 1. Bournemouth, British Herbal Medicine Association, 1992:199–203.

9. Newton LE. In defence of the name Aloe vera. The cactus and succulent journal of Great Britain, 1979, 41:29–30.

10. Tucker AO, Duke JA, Foster S. Botanical nomenclature of medicinal plants. In: Cracker LE, Simon JE, eds. Herbs, spices and medicinal plants, Vol. 4. Phoenix, AR, Oryx Press, 1989:169–242.

11. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, August 8, 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. Youngken HW. Textbook of pharmacognosy, 6th ed. Philadelphia, Blakiston, 1950.

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

14. The Indian pharmaceutical codex. Vol. I. Indigenous drugs. New Delhi, Council of Scientific & Industrial Research, 1953.

15. Haller JS. A drug for all seasons, medical and pharmacological history of aloe. Bulletin of the New York Academy of Medicine, 1990, 66:647–659.

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

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

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

19. 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).

20. Castleman M. The healing herbs. Emmaus, PA, Rodale Press, 1991:42–44.

21. de Witte P. Metabolism and pharmacokinetics of anthranoids. Pharmacology, 1993, 47(Suppl. 1):86–97.

22. Ishii O, Tanizawa H, Takino Y. Studies of Aloe III. Mechanism of laxative effect. Chemical and pharmaceutical bulletin, 1990, 38:197–200.

23. Tyler VE, Bradley LR, Robbers JE, eds. Pharmacognosy, 9th ed. Philadelphia, Lea & Febiger, 1988:62–63.

24. Tyler VE. Herbs of choice. New York, Pharmaceutical Products Press, 1994:155–157.

25. Che QM et al. Isolation of human intestinal bacteria capable of transforming barbaloin to aloe-emodin anthrone. Planta medica, 1991, 57:15–19.

26. Aloe capensis, Cape Aloes: proposal for the summary of product characteristics. Elburg, Netherlands, European Scientific Committee of Phytotherapy, 1995.

27. Reynolds JEF, ed. Martindale, the extra pharmacopoeia, 30th ed. London, Pharmaceutical Press, 1993:903.

28. Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York, McGraw Hill, 1990.

29. Bisset NG. Sennae folium. In: Max Wichtl's herbal drugs & phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994:463–469.

30. American Hospital Formulary Service. Bethesda, MD, American Society of Hospital Pharmacists, 1990.

31. United States pharmacopeia, drug information. Rockville, MD, United States Pharmacopeial Convention, 1992.

32. Siegers CP et al. Anthranoid laxative abuse-a risk for colorectal cancer. Gut, 1993, 34:1099–1101.

33. Siegers CP. Anthranoid laxatives and colorectal cancer. Trends in pharmacological sciences, 1992, 13:229–231.

34. Patel PM et al. Anthraquinone laxatives and human cancer. Postgraduate medical journal, 1989, 65:216–217.

35. Loew D. Pseudomelanosis coli durch Anthranoide. Zeitschrift für Phytotherapie, 1994, 16:312–318.

36. Lang W. Pharmacokinetic–metabolic studies with 14C-aloe emodin after oral administration to male and female rats. Pharmacology, 1993, 47(Suppl. 1):73–77.

37. Brown JP. A review of the genetic effects of naturally occurring flavonoids, anthraquinones and related compounds. Mutation research, 1980, 75:243–277.

38. Westendorf J et al. Genotoxicity of naturally occurring hydroxyanthraquinones. Mutation research, 1990, 240:1–12.

39. Bangel E et al. Tierexperimentelle pharmakologische Untersuchungen zur Frage der abortiven und teratogenen Wirkung sowie zur Hyperämie von Aloe. Steiner- Informationsdienst, 1975, 4:1–25.

40. Lewis JH, Weingold AB. The use of gastrointestinal drugs during pregnancy and lactation. American journal of gastroenterology, 1985, 80:912–923.

41. Beuers U, Spengler U, Pape GR. Hepatitis after chronic abuse of senna. Lancet, 1991, 337:472.

42. Muller-Lissner SA. Adverse effects of laxatives: facts and fiction. Pharmacology, 47, 1993, (Suppl. 1):138–145.

43. Godding EW. Therapeutics of laxative agents with special reference to the anthraquinones. Pharmacology, 1976, 14(Suppl. 1):78–101.

44. Heizer WD et al. Protein-losing gastroenteropathy and malabsorption associated with factitious diarrhoea. Annals of internal medicine, 1968, 68:839–852.

45. Goodman and Gilman's the pharmacological basis of therapeutics, 9th ed. New York, McGraw Hill, 1996.

46. Kune GA. Laxative use not a risk for colorectal cancer: data from the Melbourne colorectal cancer study. Zeitschrift für Gasteroenterologie, 1993, 31:140–143.

 

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