Aloe is a medicinal plant that has maintained its popularity over the course of time. Three distinct preparations of aloe plants are mostly used in a medicinal capacity: aloe latex (=aloe); aloe gel (=aloe vera); and, aloe whole leaf (=aloe extract). Aloe latex is used for its laxative effect; aloe gel is used topically for skin ailments, such as wound healing, psoriasis, genital herpes and internally by oral administration in diabetic and hyperlipidaemic patients and to heal gastric ulcers; and, aloe extract is potentially useful for cancer and AIDS. The use of honey may make the aloe extract therapy palatable and more efficient.
Aloe preparations, especially aloe gel, have been reported to be chemically unstable and may deteriorate over a short time period. In addition, hot water extracts may not contain adequate concentrations of active ingredients and purified fractions may be required in animal studies and clinical trials. Therefore it should be kept in mind that, in some cases, the accuracy of the listed actions may be uncertain and should be verified by further studies.
There are at least 600 known species of Aloe (Family Liliaceae), many of which have been used as botanical medicines in many countries for thousands of years. Species of the genus Aloe are indigenous to Africa (Aloe ferox Miller, A. africana Miller, A. spicata Baker, A. platylepis Baker, A. candelabrum Berger) and Socotra (Aloe perryi Baker, A. forbesii Balf.fil.). Some have been introduced in Asia (A. chinensis Baker), the Barbados Islands in Central America (Aloe barbadensis Miller, otherwise known as Aloe vera [L.] Burm. or A. vulgaris Lamarck) and Europe (Aloe arborescens Miller). Aloe ferox, known in commerce as ‘Cape aloe,’ is easy to hybridise and cultivate in Africa. The term ‘Cape aloe,’ for accuracy, refers to the dried latex of the leaves of several species of the Aloe genus, especially Aloe ferox, and the hybrids and preparations made from them. Aloe barbadensis, known in commerce as ‘Curacao aloe,’ was said to be native to northern Africa but was introduced into the Barbados Islands in the seventeenth century and is now cultivated in Florida, USA. A. chinensis, a variety of Aloe vera, was introduced into Curacao from China in 1817 by Anderson. The plant was cultivated in the Barbados Islands until the end of the nineteenth century. Curacao aloe is often called Barbados aloe. Other varieties are cultivated throughout India while some grow wild on the coasts of Bombay, Gujarat, southern Arabia, Madagascar and areas surrounding the Red Sea and the Mediterranean Sea. At the present time the principal areas for production of aloes are South Africa, Venezuela, Haiti, Florida and the Dutch islands of Aruba and Bonaire. The plant grows very well if adequately protected from cold weather; aloes are injured at 2 °C and generally killed at -1°C.
The genus Aloe includes trees (e.g. Aloe ferox) of variable height (from 2 to 15 metres), shrubs and herbs (Aloe barbadensis). They are succulent plants with perennial, strong and fibrous roots and numerous (15–30) large, fleshly leaves, carrying spines at the margin. In some species the leaves form a rosette at ground level (Aloe perryi). The flowers are grouped in erect, terminal spikes, and are borne by a floral stalk, which is either unique (Aloe vera) or ramified (Aloe ferox); the corolla is tubular, divided into narrow segments (six) at the mouth and of a red (Aloe perryi), yellow (Aloe vera) or white (A. speciosa Baker) colour. In some aloes (Aloe arborescens) the vascular cambium develops with age, initiating extensive secondary growth and allowing considerable lateral expansion.
Aloes resemble to some extent the agave or century plant (Agave americana L., Family Amaryllidaceae); however, the aloe plant is in flower during the greater part of the year while the agave plant is remarkable for the long interval between its periods of flowering.
Aloe leaves in section show from outer to inner: (i) a cuticularized epidermis; (ii) a parenchyma containing chlorophyll, starch and bundles of needles of calcium oxalate; (iii) large peryciclic cells; and, (iv) a central region (3/5 of the diameter of the leaf) consisting of large parenchymatous cells.
Aloe is from the Arabic alloeh or the Hebrew halal and means a shining, bitter substance (); ferox is from the Latin and means ferocious or wild; vera is from the Latin verus, meaning true; barbadensis refers to the Barbados Islands; africana, or chinensis, refers to the habitat of the plant; spicata refers to the flowers in spikes. However, the word aloe in pharmacopoeias and formularies means a drug derived from the dried leaf juice. This has always created confusion because the leaves of the genus Aloe are the source of two products that are quite different in their chemical composition and their therapeutic properties, aloe latex and aloe gel. These two products are obtained from two different specialised cells, latex from pericyclic cells and gel from parenchymatous cells. Therefore the term juice must be avoided, as it could mean either the latex from the pericyclic cells, or the gel after extraction from the leaf. There is also a preparation obtained from the whole leaf (total extract) which contains all the components present in aloe leaves. Aloes contain another medically important part, the leaf epidermis. There are also the aloe wood and the aloe root. The first preparation, so called lignaloe or aloe of the Bible, is a fragrant wood obtained from an entirely different plant that was once used as an incense. The second is a synonym of unicort root, a preparation that when dried becomes a valuable bitter tonic.
Apart from aloe wood and aloe root which have nothing to do with the genus Aloe, the other preparations have very similar names that are sometimes interchanged. Aloe in one form or another is a common domestic medicine and is the basis of most pharmaceutical preparations.
The topical and internal effects of aloes have been known since ancient times. Nefertite and Cleopatra, two Egyptian queens, used aloes as a beauty aid. The drug was used by Dioscorides to heal skin ailments and haemorrhoids. Aloes were used by Pliny the Elder, Celsus, Galen and other famous physicians to treat wounds and gastrointestinal disturbances, but no mention of aloes was made by either Hippocrates or Theophrastus. Aloe was largely prescribed by Arabian physicians and was one of the drugs-the others were balsam, scammony, tragacanth and galbanum-recommended to Alfred the Great by Helias, the Patriarch of Jerusalem. Aloe’s use was first discovered on a Mesopotamian clay tablet dating from 2100 B.C. Later, in 1862, a German egyptologist, George Ebers, discovered that a papyrus found in a sarcophagus near Thebes mentioned at least twelve preparations for preparing aloe to treat external and internal ailments.
Aloe was considered by the ancient Greeks to be an exclusive production of the island of Socotra, in the Indian Ocean. This is why Alexander the Great, persuaded by Aristotle, his mentor, captured the island of Socotra and sent to it Greek colonists solely to preserve and cultivate the aloe plant. The drug was included in the Egyptian Book of Remedies (about 1500 B.C.), as well as in that of the Hebrews, as a laxative and dermatologic preparation. Mesopotamians were also aware of its medicinal properties by that time. Aloe was first reported in Greek literature as a laxative before the first century. In the first century Dioscorides wrote of its use in treating wounds, chapping, hair loss, genital ulcers, haemorrhoids, boils, mouth irritation and inflammation. In the seventh century, aloe was also used in the Orient for eczema and sinusitis.
Aloe, when introduced into Europe, was used for constipation and skin ailments and later, in the 1930s, was used to treat radiation burns. From the ancient times to the seventeenth century the Socotrine aloe was the only official aloe. This vegetable remedy was imported into Europe by way of the Red Sea and Alexandria; there was a direct trade in aloes between Socotra and some medieval towns like Venice, which by the fifteenth century became the greatest trading centre of Europe. At the end of the seventeenth century it was possible to find aloes from the Barbados in Europe, and later, towards the end of the eighteenth century, the Cape Aloe too. The drug was included as a laxative in the U.S. Pharmacopoeia in 1820, in the Italian Pharmacopoeia in 1892 and in the European Pharmacopoeia in 1969. Today Socotrine aloes are very rare, while Barbados and Cape aloes are the most common.
In addition to its medicinal virtues, aloe was believed to be endowed with power against evil spirits. On this account, it was carefully planted in the neighbourhood of Mecca and hung by Mussulmans who visited the shrine of the Prophet, and hung over doorways as a religious symbol. The Mussulman name of aloe is saber and signifies patience, referred to the waiting-time between the burial and the resurrection morning.
Near the epidermis or outer skin the leaves of aloes contain a row of fibrovascular bundles, the cells of which are much enlarged and filled with a yellow latex. Aloe latex is obtained by cutting the leaf transversely close to the stem and inclining the leaf so that the latex flows out in about six hours.
No pressure must be applied otherwise the product will be contaminated with the mucilage present in the inner part of the leaf. The preparation obtained is bitter and yellow; it is concentrated to dryness by evaporation in open kettles, rarely by boiling in a vacuum, until it becomes a shiny mass, like broken glass with a yellow greenish to red-black colour. A slow evaporation carried out either by inappropriate temperature or by spontaneous evaporation gives an opaque mass with a wax-like fracture. The taste is nauseating and bitter and the odour sour, recalling that of rhubarb, apple-tart or iodoform.
Aloes require two or three years standing before they yield their latex. In Africa the latex is collected from the wild plants; in the case of aloe plantations the drug is collected in April/July. Aloe latex (=aloe) contains mainly anthraquinones, cathartic compounds useful in constipation. It is totally different from the aloe gel (=aloe vera), a colourless gelatin obtained from the central portion of aloe leaf. The mucilaginous parenchyma tissue is excised from fresh leaves and immediately utilised for pharmaceutical preparations or lyophilized and kept dry until use. During extraction of the gel it is practically impossible to prevent contamination by the latex as the leaves are cut. On the other hand in intact leaves, anthraquinones may diffuse into gel from the bundle sheath cells. To reduce such contamination the starting material must be from varieties of Aloe with a reduced anthraquinone content. Aloe gel is sensitive to heat and light and can quickly deteriorate when exposed at high temperature. It contains mainly mucilage and it is now a familiar ingredient in cosmetics and ointments for skin ailments. Some recent observations have proven that the rind and the outer leaf, normally thrown away, contain greater healing components.
The fresh whole leaf is also cut into small pieces and whipped in order to obtain a homogenous yellowish or reddish material. The preparation (total leaf extract = aloe extract) is bitter and has a very characteristic odour. Finally, it has been reported that the leaf epidermis of Aloe arborescens contains lectin, a product that is able to inhibit the growth of a fibrosarcoma in animals through a host-mediated effect. This could stimulate further research and give rise to a new medicinal preparation.
Aloes contain anthraquinone derivatives (10% to 40%) like aloin, mucilage (30%), resinous substances (16% to 63%) like aloesin and aloesone, sugars (about 25%), polysaccharides like acemannan and betamannan, fatty acids and cholesterol, campesterol, β-sistosterol, glycoproteins (aloctins A and B), lectins, a gibberellin-like substance, enzymes such as cyclo-oxygenase and bradykininase, together with other compounds such as lupeol, salicylic acid, urea, cinnamic acid, phenol, sulphur, magnesium lactate, salicylates, and amino acids. Aloin (=barbaloin) is an impure mixture of barbaloin A and barbaloin B, which inter-convert through the anthranol form.
Anthraquinone derivatives possess laxative properties; their content is subject to seasonal variations. Aloins reach a maximum concentration in the dried leaf latex of Aloe ferox in April-July [24.1%] and a minimum concentration in winter [14.8%]. 5-hydroxyaloin A, characteristic of Cape aloe, is absent in Curacao aloe. However, studies carried out on plants grown hydroponically under carefully controlled conditions still show these variations; for example, aloin content can vary as much as 80% from one plant to another in the same field. Aloes also contain other healing components such as analgesic and anti-inflammatory agents, (aloctins, cholesterol, campesterol, β-sitosterol, acemannan, salicylates, etc.), immunostimulant agents, (acemannan, lectin, etc.) and antiseptic agents (lupeol, salicylic acid, phenol, sulphur, etc.). The benefits of aloe are, however, due to synergism between compounds; also, it is quite possible that other unidentified co-factors present in aloe may provide for the optimum effects generally encountered.
Adverse Effects, Toxicity, Drug Interaction
Aloe latex (laxative use)
Aloe latex may cause abdominal complaints, meteorism, flatulence, cramps and abdominal pain, just like other laxative drugs such as senna, rhubarb, etc., which are digested by colon microflora. However, because constipation is often associated with abdominal discomfort, the causative role of aloe is not always apparent. Other side-effects include hemorrhoid congestion and coloration of the urine which becomes orange if the pH is acidic, or reddish purple if the pH is alkaline. This is caused by the renal excretion of the hydroxyanthracene derivatives. An overdosage may cause nephritis, vomiting, bloody diarrhoea with mucus and hemorrhagic gastritis. Prolonged use or overdosage may result in watery diarrhoea leading to electrolyte imbalance. The increased intestinal loss of K+ can lead to hypokalemia, while Na+ loss can result in secondary hyperaldosteronism. This can exacerbate renal K+ excretion, leading to further reduction of colonic motility. This situation results in fatigue, muscular weakness, weight loss, mental disturbances, steatorrhoea, electrocardiographic abnormalities and kidney dysfunction.
Hypokalemia, which results from K+ loss, may potentiate the action of digoxin, a cardiac glycoside. Drugs like thiazide diuretics, corticosteroids and licorice may exacerbate hypokalemia. Table “Aloe – drug interactions” lists other possible interactions regarding both aloe latex and aloe gel. Damage to surface epithelium and an impairment of function following damage to the autonomic nervous system may also develop. These changes, however, have not been clearly demonstrated in animals and humans.
The abuse of aloe has been associated with melanosis coli, which consists of a mahogany to dark brown coloration of the intestinal mucosa that begins at the ileocolonic junction and may extend to the rectum. The morphological basis of melanosis is a pigment, probably lipofuscin, within macrophages of the large intestinal mucosa. A correlation between the intake of laxative and melanosis is accepted now but there is no indication that melanosis has any pathophysiological consequences. On the other hand the intestinal mucosa recovers its usual coloration 4–12 months after the intake of the laxative has stopped.
Habituation has not been proved for aloe. Indeed studies in rats suggest that long-term aloe treatment (three to six months) does not induce tolerance in the sense of a reduced laxative effect.
Anthraquinone derivatives have shown genotoxicity in Salmonella assay but the clinical relevance of this experimental result is still not clear. On the other hand, due to the artificial nature of these methods many flavonoids (quercetin, galangin, kaempferol) and antioxidants, including vitamin C, have produced genotoxic effects under these conditions.
In recent years the risk of colon cancer has been found to be related to constipation and to use of anthraquinone laxatives but epidemiological studies are in disagreement. Jacobs and White, in a recent study, reported that when the colon cancer risks for constipation and laxatives were adjusted for each other, the association with laxatives disappeared, whereas the association with constipation remained strong. Other retrospective data related to laxative use did not show any significant increase of colon cancer incidence. It has also been demonstrated that a positive correlation between melanosis coli, a marker for chronic abuse of anthranoid laxatives, and colon carcinoma exists but this correlation failed in another retrospective study. A study carried out in vivo shows that aloe given alone for 13 weeks did not induce the development of preneoplastic or neoplastic lesions, or Aberrant Crypt Foci (ACF), and therefore this laxative did not display any tumor initiating activity in the rat colon. In addition, when aloe was administered with AOM (azoxymethane), a carcinogen agent, it did not produce any significant increase of ACF, and tumors. These results are basically in agreement with previous studies carried out with other anthraquinone drugs. Recent studies have also shown that anthraquinone compounds (i.e. emodin) selectively block the retardation of oncogene-modulated signal transduction through the inhibition of protein kinase. All these results suggest a sufficient margin of safety for aloe and other anthraquinone drugs when used internally. The FDA has recently proposed to stop the use of aloe, the laxative, until further studies can show its benefit and safety.
Toxicity due to oral and topical use of Aloe vera
Several studies have been made to determine whether aloe causes toxicity in animals or humans in gel form or in its various preparations, pure gel, liquid concentrate, etc. Studies in mice revealed no acute toxicity in therapeutic doses. In high doses, however, a decrease of CNS (central nervous system) activity was noticed. During chronic treatment, there was a decrease in red cell count and significant sperm damage. On the other hand if aloe gel contains very large amounts of aloin, it may cause unfavourable side-effects. In spite of its wound-healing and anti-inflammatory properties, the topical application of aloe gel has been reported in the literature to cause contact and photodermatitis and/or erythema with papulous. Aloin can certainly irritate the skin. However it has been recently found that painting aloe emodin on the skin of mice in conjunction with exposure to ultraviolet radiation results in the development of melatonin-containing skin tumors. The precise contribution of aloe derivatives to the development of cutaneous melanoma requires further definition. In the meantime it is preferable to avoid local application of aloe gel when the skin is exposed to ultraviolet radiation. One case of cathartic effect after topical application of aloe gel has also been reported.
Vogler & Ernst, by reviewing ten controlled clinical trials — a total of 803 subjects-reported no withdrawals or serious adverse reactions. Some patients experienced burning after topical application, contact dermatitis and mild itching. All adverse effects were reversible and aloe vera was generally well tolerated.
Healing Powers of Aloes: Conclusions
Aloe and its preparations have been widely used as a medicine since ancient times. Its beneficial effects are mentioned in Hebers Papyrus and in the writings of famous physicians, from Dioscorides to Galen. Aloe has been a common folk medicine in several countries. The whole plant has been used in India as a stomachic, antihelmintic, emmenagogue and purgative; the leaf pulp has also been used for menstrual suppression and the root for colic. In China it is a common dermatological remedy and in Mexico it is used to treat minor skin irritations. Aloe has also been used for centuries for a multiplicity of unrelated human illness: for example to correct kidney ailments, to enhance sexual excitement, to develop the mammary glands, to relieve headaches and reduce fever in children. Two uses, however, have persisted for centuries: the main one, internal, has been as a laxative; the second, external, in the treatment of skin injuries. The use of aloe orally, other than for its well-accepted laxative effect, needs furthers studies. Aloe gel can be applied liberally for topical applications. Now a wide range of products are available on the market; however, simply pure aloe gel is sufficient. This product is very sensitive to light and heat, therefore it is removed from the leaf mechanically and preserved, buffered and stabilised immediately. This process may differ from manufacturer to manufacturer, making the quality of aloe gel highly variable. This variation in quality must be responsible for some of the negative or inconclusive studies. In addition aloe gel is unstable and may deteriorate in a short time period, which may also explain some of the conflicting study results.
A recent systematic review suggests that oral administration of aloe gel might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia. Topical application of aloe vera is not an effective preventative for radiation-induced injuries. It might be effective for genital herpes and psoriasis. Whether it promotes wound healing is unclear.
Clinical trials are now in progress to provide conclusive evidence not only in these diseases but also in arthritis, gastric ulcer, cancer, AIDS and colitis. However, this is not easy to perform, because there is still confusion about aloe preparations. It is not enough to say that a preparation, if not specified as a latex or gel, is referred to as an extract. Aloe products are classified as drugs while others as dietary supplements. Aloe is also a common ingredient in numerous hand, body and sun lotions, shaving creams, shampoos and personal care-products. This is why people sometimes forget to consider aloe a medicinal drug. Aloe is also processed into various flavoured and unflavoured alcoholic drinks (.) that are ingested with the belief that this bitter liquid (amarum) will stimulate the appetite and/or the digestion. There is a general conviction that bitters also have a tonic effect on the body and the term ‘bitter tonic’ is often used. Finally for its very bitter taste aloe has been widely used to discourage nail biting.
Selections from the book: “Aloes. The genus Aloe”. Edited by Tom Reynolds. Series: “Medicinal and Aromatic Plants — Industrial Profiles”. 2004.