Aloe barbadensis – a legendary medicinal plant

Fig. 1. Aloe barbadensis Miller. Plantation in southern California. Photo: © H B Juneby.

Hans B. Juneby

Pharmacognosy, 15 hp, 2009

Supervisor: Jenny Felth Division of Pharmacognosy

Department of Medicinal Chemistry Uppsala University, Sweden

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Summary

Aloe barbadensis (Aloe vera) is native to the Mediterranean region of southern Europe and North Africa and to the Canary Islands. It is commonly grown in Asia, southern Europe, southern USA, Mexico, Aruba, Bonaire, Bermuda, the Bahamas, West Indies, Central and South America. The medicinal use of aloe was already mentioned more than 4000 years ago in a collection of Sumerian clay tablets dated 2100 BC. Aloe was also mentioned as a laxative in the Egyptian Papyrus Ebers from 1552 BC. Aloe has had a very long historical use as a strong laxative treatment for chronic constipation, and it is still listed as a laxative in many pharmacopoeias. However, it has now been largely superseded by less toxic laxatives. Today there are hundreds of different medicinal, cosmetic and food products on the market that contain various amounts of non-laxative aloe juice/gel. The aloe content has become an important marketing factor which capitalizes on the legendary fame of this medicinal plant. However, there are many aloe products of a questionable quality on the market, which has led to the foundation of a product quality certification program, administered by the International Aloe Science Council. Externally, fresh aloe gel from the inner central part (parenchyma) of the leaf often has a very good effect in acne, pimples, eczema and other skin problems, poorly healing wounds, leg ulcers, burns due to excessive heat, sun exposure and in the treatment of radiation dermatitis. Internally, aloe juice can be used in gastro-enteritis and peptic ulcers. The dried latex, with high barbaloin content, is a strong laxative. The best way to benefit from the healing properties of Aloe vera is probably to keep a potted plant in the house and use the gel from a fresh leaf whenever it is needed to treat minor burns and other conditions where it may have some medicinal value. This will also eliminate the need to worry about the quality and medicinal value of some commercial product.

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Contents

1 Introduction ....................................................................................................... 4 2 Monograph on Aloe barbadensis ........................................................................ 5 2.1 Name ................................................................................................................ 5 2.2 Habitat ............................................................................................................. 5

2.3 Parts used ........................................................................................................ 5 2.4 Active ingredients .......................................................................................... 7 2.5 Pharmacology ................................................................................................. 7 2.6 Interactions ...................................................................................................... 8 2.7 Toxicology ........................................................................................................ 8 2.8 Medicinal use .................................................................................................. 8 2.9 Preparations and dosages ............................................................................. 9 3 Discussion ......................................................................................................... 10 4 References .......................................................................................................... 11

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1 Introduction

The medicinal use of aloe was already mentioned more than 4000 years ago in a collection of Sumerian clay tablets dated 2100 BC (Kramer, 1954). Aloe was also mentioned as a laxative in the Egyptian Papyrus Ebers from 1552 BC (Taylor, 1965). Aloe has had a very long historical use as a strong laxative treatment for chronic constipation, and it is still listed as a laxative in the following pharmacopoeias: Austrian, British, Brazilian, Egyptian, European, French, German, Greek, Hungarian, Italian, Japanese, Netherlands, Nordic, Portuguese, Romanian, Swiss, Turkish and U.S. However, it has now been largely superseded by less toxic laxatives (Reynolds, 1993). According to a famous legend, Alexander the Great sent a commission to the Island of Socotra in the year 333 BC to investigate the local aloe production. The report was favorable, which prompted Aristotele, in 325 BC, to urge his protegé Alexander the Great to conquer the Island of Socotra in the Arabian Sea, to make medicinal aloe available for healing the battle wounds of his troops (El Zawahry et al., 1973; Lindeberg et al., 1982). The historically documented medical use of aloe was as a laxative. According to Danhof (1987, p. 93), ”the supposed use of fresh internal gel of the leaves for battle wounds of Alexander's men is wholely unsupported, but does make a fine story!” According to another legend, Queen Nefertiti of the 14th century BC in Egypt used the internal aloe gel as a beauty aid. Danhof (1987, p. 82) remarks that, ”it does make a good story for a lady whose likeness is well known today, and who is highly regarded as the epitome of feminine beauty. Certainly, the ill-smelling dried yellow latex or sap would have no appeal as an aid in accentuating beauty.” The legend also claims that famous Queen Cleopatra of the 1st century BC also used aloe gel as a beauty aid. Today there are hundreds of different medicinal, cosmetic and food products on the market that contain various amounts of juice/gel from Aloe barbadensis. The aloe content has become an important marketing factor which capitalizes on the legendary fame of this medicinal plant. However, there are many aloe products of a questionable quality on the market, which in the early 1980's led to the foundation of a product quality certification program, administered by the International Aloe Science Council (IASC). In March 2009 the IASC had certified about 500 finished aloe products and raw materials from more than 80 companies worldwide, but there are hundreds of other aloe products on the marked which are not certified (IASC 2009).

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2 Monograph on Aloe barbadensis

Fig. 2. A newly harvested aloe leaf from a plantation in southern California. Photo: © H B Juneby.

2.1 Name

Aloe vera, Aloe barbadensis Miller. Synonyms: Aloe vera Tourn. ex L. Aloe perfoliata var vera L., Aloe elongata Murry, Aloe vulgaris Lamarck, Aloe flava Pers. (Danhof, 1987). Aloe belongs to the lily family, Liliaceae.

2.2 Habitat

Native to the Mediterranean region of southern Europe and North Africa and to the Canary Islands. Commonly grown in Asia, southern Europe, southern USA, Mexico, Aruba, Bonaire, Bermuda, the Bahamas, West Indies, Central and South America (Morton, 1977). 2.3 Parts used

The largest leaves, which grow closest to the ground, are harvested by cutting with the point of a knife at the constricted base, close to the stem. This avoids undue leakage of latex and allows the leaf to self-seal and remain in good condition for two or three weeks without refrigeration (Morton, 1977).

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An aloe plant may mature in one year with ideal climate, exposure to sunlight, water supply, soil nutrients, etc. Harvesting may begin the second year, with a leaf reaching maturity every one to three months. With less ideal conditions, full maturity may not be reached until the plant is three or four years old. An aloe plant usually produces optimally for five or six years, but may continue to produce at least twice as long. In commercial aloe plantations, three leaves of about one kilogram (two pounds) each in weight and 50 – 75 cm (20 – 30 inches) in length are harvested three or four times a year (Danhof, 1987).

Fig. 3. The inner mucous leaf parenchyma. Photo: © H B Juneby.

Aloe succus (Aloe juice/gel) – Fresh stabilized viscous juice/gel from the inner central part (parenchyma) of the leaf. It is best removed by hand to avoid admixture of aloin from the pericycle cells located just under the leaf epidermis. Aloe – dried (inspissated) latex from the superficial pericycle cells with a high aloin content. The cut leaves are stacked face down with the base inward around the perimeter of a pit lined with an animal hide or a canvas. The latex seeps out continuously from the leaves for about six hours and it is later concentrated by boiling or drying in the sun Morton, 1977; Wagner, 1993).

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2.4 Active ingredients

Fresh aloe juice/gel from the inner leaf parenchyma contains 96% water, poly-saccharides (mucilage) consisting mainly of D-glucose and D-mannose, tannins, steroids, enzymes, plant hormones, amino acids, vitamins, minerals, and a small amount of barbaloin. The dried latex from the superficial pericycle cells contains at least 28% hydroxyanthracene, calculated as anhydrous barbaloin, which is a mixture of aloin A and aloin B, resin and saponins (Bradley, 1992; Steinegger & Hänsel, 1988; Wagner, 1993; Sandberg & Bohlin, 1993; Samuelsson, 2004). 2.5 Pharmacology

Barbaloin resembles the anthraquinone glycosides in Senna and have a strongly irritating effect on the intestine, increasing peristalsis and having a strong laxative effect (Reynolds, 1993; Wagner, 1993). A local application is effective against itching (Fantus, 1922). There are no published studies on the pharmacokinetics and metabolism of barb-aloin. Juice/gel from the inner leaf parenchyma contains very small amounts of barbaloin and only has a very mild laxative effect (Steinegger & Hänsel, 1988).

The mucilage (gelatinous polysaccharides) mainly has a local effect on the skin and mucous membranes at direct contact, because they can form a barrier that protects against mechanical and chemical irritation. This property is very useful in the treatment of poorly healing wounds, burns, gastro-enteritis and peptic ulcers. The application of aloe gel on burns quickly relieves pain, reduces the severity of the burn, accelerates healing and prevents scar formation (Danhof, 1987).

According to a recent study, “Simultaneous application of Aloe vera gel and microcurrent is an excellent choice for the treatment of open wounds thus indicating a synergistic action of these two applications.” (Mendonça et al., 2009).

Fresh aloe gel has an anti-inflammatory effect (inhibits the synthesis of prosta-glandin) which may be due to a combination of the substances magnesium silicate, bradykinase and the glucoprotein aloctin A (Wagner, 1993). A combination of aloe gel and cortisone enhances the anti-inflammatory effect of the hormone on the skin (Davis et al., 1991). A recent study indicates that aloin and aloe-emodin may be a key constituent responsible for the anti-inflammatory effect of aloe (Park et al., 2009). Skin damage from radiation treatments has successfully been treated with aloe gel (McLaughlin, 1936; Morton, 1961; Goyal & Gehlot, 2009).

Fresh aloe juice has a very interesting property. It enhances the growth of human cells in cell cultures and speeds the healing of damaged tissue. On the other hand, the aloe gel contained in cosmetic products has been shown to have a negative effect on the healing process (Winters et al., 1981).

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Another study used tissue cultures with human fibroblasts, to which was added various concentrations (0.01 – 0.3%) of yellow aloin rich latex from the aloe leaf's superficial pericycle cells compared to the addition of aloe gel from the inner leaf parenchyma. It turned out that all concentrations of aloin latex killed all the cells in the culture while aloe gel stimulated cell growth by up to 882% at the highest (0.3%) gel concentration (Danhof & McAnalley 1983; Danhof, 1984). Aloe and other plants that contain anthraquinones have an antiseptic effect against a number of bacteria and fungi, e.g. staphylococci, streptococci, salmonella bacteria and Candida albicans fungi (Steinegger & Hänsel, 1988; Duke, 1997). It has even been suggested that administration of Aloe vera could be a potential therapeutic agent for the clinical treatment of sepsis, which is an acute life-threatening condition, which remains the major cause of death in intensive care units (Yun et al., 2009). Another study suggests that Aloe vera “could inhibit infectious diseases by stimulating the host defense mechanism, especially the phagocytic and killing activities of macro-phages.” (Tamura et al., 2009). The enzymes in aloe are destroyed at temperatures above 70° C. Fresh leaves and carefully made extracts therefore have the greatest effect, while heated, powdered dry extracts have much weaker, or even negative effects (Winters et al., 1981; Schmidt & Greenspoon, 1991). Aloe juice has a blood-sugar lowering effect and also enhances the effect of the oral diabetes drug Glibenklamid (Yongchaiyudha et al., 1996; Bunyapraphatsara et al., 1996). Fourty published clinical trials, in vitro and in vivo studies on the effects of Aloe vera were recently analyzed, which resulted in the following observations (Feily & Namazi, 2009):

“The results suggest that oral administration of aloe vera in mice is effective on wound healing, can decrease the number and size of papillomas and reduce the incidence of tumors and leishmania parasitemia by >90% in the liver, spleen, and bone marrow. Topical application of aloe vera is not an effective prevention for radiation-induced injuries and has no sunburn or suntan protection. It can be effective for genital herpes, psoriasis, human papiloma virus, seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus, frostbite, burn, wound healing and inflammation. It can also be used as a biological vehicle and an anti-microbial and antifungal agent and also as a candidate for photodynamic therapy of some kinds of cancer.”

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2.6 Interactions As previously mentioned, aloe juice enhances the hypoglycemic effect of Gliben-clamide when it is given to diabetes patients (Yongchaiyudha et al., 1996; Bunyapraphatsara et al., 1996) and improves the local anti-inflammatory effect of cortisone (Davis et al., 1991). Aloe vera gel contains water soluble, hydrocolloidal plant fibers that delay gastric emptying and create a mucilaginous intestinal environment, which inhibits the absorption of dietary and pharmaceutical agents. Overuse or misuse of laxative aloe preparations can cause excessive potassium loss, leading to increased toxicity of drugs containing cardiac glycosides (Wichtl, 1989; Meletis & Jacobs, 1999). 2.7 Toxicology The dried latex from the superficial pericycle cells has the same side effects as other peristalsis stimulating laxatives, but aloe has a more drastic and irritant action than Senna (Reynolds, 1993). Aloe is contra-indicated during pregnancy, menstruation and hemorrhoids due to hyperemia of the pelvic organs (Wagner, 1993). An overdose may cause severe abdominal pain, bleeding gastritis and inflammation of the kidneys (Leung, 1980). However, the fresh aloe juice/gel normally does not give any side effects. Occasionally the local application of aloe gel may cause an acute skin rash, which usually soon disappears with continued use (Juneby, 1999). 2.8 Medicinal use Externally, fresh aloe gel often has a very good effect in acne, pimples, eczema and other skin problems, poorly healing wounds, leg ulcers, burns due to excessive heat, sun exposure and in the treatment of radiation dermatitis. Internally, aloe juice can be used in gastro-enteritis and peptic ulcers. The dried latex, with a high barbaloin content, is a strong laxative, but its use should be limited to no more than one week, and it should not be used during menstruation, pregnancy and nursing. The suggested medicinal use of Aloe vera is based on its historic and traditional use, and an analysis of modern pharmacologic and toxicologic research (Juneby, 1999). See also the additional information under pharmacology, interactions and toxicology.

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2.9 Preparations and dosages

Aloe succus (juice/gel), 15 – 30 ml. 1 – 2 tablespoons are taken on an empty stomach or between meals 2 – 3 times a day. Externally the gel is applied to the affected area 2 – 3 times a day as needed. As a laxative, 50 – 300 mg aloe powder or a dry extract is taken in the evening for temporary constipation (Bradley, 1992; Wagner, 1993).

Fig. 4. From left to right: Aloe vera concentrated juice/gel (a raw material) and a sun burn gel from Florida, USA. Aloe vera gel and a soap bar from Sweden. Photo: © H B Juneby.

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3 Discussion Reynolds (1993, p. 869), makes the following critical observations about the uses and administration of Aloe vera gel, referring to critical articles by Hecht (1981) and Marshall (1990):

“It is widely used in cosmetics and toiletries for a reported moisturising and revitalising action. There are also now claims for the beneficial and even curative properties of aloe vera gel in the self-treatment of medical conditions such as acne, hemorrhoids, psoriasis, anemia, arthritis, burns, cancer, depres-sion, diabetes, glaucoma, multiple sclerosis, peptic ulcer, tuberculosis, and even blindness. There is no evidence to support these claims.”

This negative view is at one extreme end of the question about the medicinal value of Aloe vera gel. At the other extreme is the view that the aloe juice/gel is a veritable panacea, which can be used to cure a great number of more or less serious ailments. As usual, the truth can most likely be found somewhere in the middle between the two extremes. There is good evidence that fresh juice/gel from recently harvested aloe leaves has a local anti-inflammatory and healing effect on skin that has been damaged by sun exposure, etc. The presence of small amounts of barbaloin has an antiseptic effect, which may help the healing process by reducing the risk of infection. There are also other medicinal uses which have been quite well documented (Danhof, 1987). Many commercial Aloe vera products have a quality that has been certified, but many others are not certified and may be of a questionable quality. This may explain why there are so many conflicting reports about the medicinal value of these medicinal, cosmetic and food products. The best way to benefit from the healing properties of Aloe vera is probably to keep a potted plant in the house and use the gel from a fresh leaf whenever it is needed to treat minor burns and other conditions where it may have some medicinal value. This will also eliminate the need to worry about the quality and medicinal value of some commercial product.

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4 References Bradley, P.R. British Herbal Compendium, British Herbal Medicine Association: Bournemouth, UK 1992. Braun, H. & Frohne, D. Heilpflanzen-Lexikon für Ärzte und Apotheker, Gustav Fischer Verlag: Stuttgart, Germany 1987. Bunyapraphatsara, N., Yongchaiyudha, S., Rungpitarangsi, V., Chokechaijaroenporn, O. Antidiabetic activity of Aloe vera L. juice, II - Clinical trial in diabetes mellitus patients in combination with glibenclamide, Phytomed 1966, 3, 245-248. Danhof, I.E. & McAnalley, B.H. Stabilized Aloe vera: Effect on human skin cells, Drug &

Cosmet Indust 1983, 133, 52, 54, 105-106. Danhof, I.E. Aloe vera components possessing cosmetic and medical applications, Abstr. Scientific Seminar, Soc Cosmet Chem, Anaheim, California, May 10-11, 1984. Danhof, I.E. Remarkable Aloe: Aloe Through the Ages – Volume One, Omnimedicus Press: Grand Prairie, Texas, USA 1987. Davis, R.H., Parker, W.L., Murdoch, D.P. Aloe vera as a biologically active vehicle for hydrocortisone acetate, J Am Podiatric Med Assoc 1991, 81, 1-9. Hecht, A. The overselling of aloe vera. FDA Consumer 1981, 15, 26-29. Lindeberg, I, et al. Örtmedicin och växtmagi, Reader’s Digest AB: Stockholm 1982. Duke, J.A. The Green Pharmacy, Rodale Press Inc: Emmaus, Pennsylvania 1997. El Zawahry, M.E., Hegazy, M.R., Helal, M. Use of aloe in treating leg ulcers and dermatoses, Dermatology 1973, 12, 68-73. Fantus, B. Aloes as a medicine, J Am Pharm Assoc 1922, 11, 616-619. Feily, A., Namazi, M.R. Aloe vera in dermatology: a brief review, G Ital Dermatol

Venereol 2009, 144, 85-91. Goyal, P.K., Gehlot, P. Radioprotective effects of Aloe vera leaf extract on Swiss albino mice against whole-body gamma irradiation, J Environ Pathol Toxicol Oncol 2009, 28, 53-61. IASC, The International Aloe Science Council Certification Program. URL: http://iasc.org/certify.html 2009-05-15.

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Juneby, H.B. Fytomedicin – en fickhandbok om medicinalväxter, Artaromaförlaget: Gamleby, Sweden 1999. Kramer, S.N. First pharmacopeia in man’s recorded history, Am J Pharm 1954, 126, 76-84. Leung, A.Y. Encyclopedia of common natural ingredients used in food, drugs and cosmetics, Wiley: New York 1980. Marchall, J.M. Aloe vera gel: what is the evidence? Pharm J 1990, 244, 360-362. McLaughlin, R. Roentgen ray dermatitis treated with ointment containing viosterol, Arch

Dermatol & Syphilol 1936, 34, 901-903. Meletis, C.D. & Jacobs, T. Interactions Between Drugs & Natural Medicines, Eclectic Medical Publications: Sandy, Oregon, USA 1999. Mendonça, F.A., Passarini Junior, J.R., Esquisatto, M.A., Mendonça, J.S., Franchini, C.C., Santos,,G.M. Effects of the application of Aloe vera (L.) and microcurrent on the healing of wounds surgically induced in Wistar rats. Acta Cir Bras 2009, 24, 150-155. Morton, J.F. Folk uses and commercial exploitation of Aloe vera leaf pulp, Econ Bot 1961, 15, 311-319. Morton, J.F. Major Medicinal Plants, Charles C. Thomas – Publisher: Springfield, Illinois, USA 1977. Park, M.Y., Kwon, H.J., Sung, M.K. Evaluation of aloin and aloe-emodin as anti-inflamma-tory agents in aloe by using murine macrophages. Biosci Biotechnol Biochem 2009, 73, 828-832. Reynolds, E.F. (Ed.) Martindale: The Extra Pharmacopoeia, The Pharmaceutical Press: London 1993. Samuelsson, G. Drugs of Natural Origin: A textbook of pharmacognosy, Swedish Pharmaceutical Society, Swedish Pharmaceutical Press: Stockholm, Sweden 2004. Sandberg, F. & Bohlin, L. Fytoterapi – Växtbaserade läkemedel, Hälsokostrådets förlag AB: Stockholm, Sweden 1993. Schmidt, J.M. & Greenspoon, J.S. Aloe vera dermal wound gel is associated with a delay in wound healing, Obstet Gynecol 1991, 78, 115-117. Steinegger, E. & Hänsel, R. Lehrbuch der Pharmakognosie und Phytopharmazie, Springer-Verlag: Berlin – Heidelberg – New York 1988. Tamura, N., Yoshida, T., Miyaji, K., Sugita-Konishi, Y., Hattori, M. Inhibition of infectious diseases by components from Aloe vera, Biosci Biotechnol Biochem 2009, 73, 950-953.

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Taylor, N. The Cathartic Racket – A Bitter Purge, in Plant Drugs That Changed the World, Dodd, Mead & Company: New York 1965; pp 158-160. Wagner, H. Pharmazeutische Biologie – Drogen und ihre Inhaltstoffe, Gustav Fischer Verlag: Stuttgart – New York 1993. Wichtl, M. Teedrogen: ein Handbuch für die Praxis auf wissenschaftlicher Grundlage, Wissenschaftliche Verlagsgesellschaft: Stuttgart, Germany 1989. Yongchaiyudha, S., Rungpitarangsi, V., Bunyapraphatsara, N., Chokechaijaroenporn, O. Antidiabetic activity of Aloe vera L. juice, I - Clinical trial in new cases of diabetes mellitus, Phytomed 1966, 3, 241-243. Yun, N., Lee, C.H., Lee, S.M. Protective effect of Aloe vera on polymicrobial sepsis in mice, Food Chem Toxicol 2009, 47, 1341-1348.