IJD_Oct-Dec_08.indd Indian J Dermatol 2008; 53(4) 163 Anatomy The plant has triangular, ß eshy leaves with serrated edges, yellow tubular ß owers and fruits that contain numerous seeds. Each leaf is composed of three layers: 1) An inner clear gel that contains 99% water and rest is made of glucomannans, amino acids, lipids, sterols and vitamins. 2) The middle layer of latex which is the bitter yellow sap and contains anthraquinones and glycosides. 3) The outer thick layer of 15�20 cells called as rind which has protective function and synthesizes carbohydrates and proteins. Inside the rind are vascular bundles responsible for transportation of substances such as water (xylem) and starch (phloem).3 Active components with its properties: Aloe vera contains 75 potentially active constituents: vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids and amino acids.4-6 1. Vitamins: It contains vitamins A (beta-carotene), C and E, which are antioxidants. It also contains vitamin B12, folic acid, and choline. Antioxidant neutralizes free radicals. 2. Enzymes: It contains 8 enzymes: aliiase, alkaline phosphatase, amylase, bradykinase, carboxypeptidase, catalase, cellulase, lipase, and peroxidase. Bradykinase helps to reduce excessive inß ammation when applied to the skin topically, while others help in the breakdown of sugars and fats. 3. Minerals: It provides calcium, chromium, copper, selenium, magnesium, manganese, potassium, sodium and zinc. They are essential for the proper functioning of various enzyme systems in different metabolic pathways and few are antioxidants. 4. Sugars: It provides monosaccharides (glucose and fructose) and polysaccharides: (glucomannans/ polymannose). These are derived from the mucilage layer of the plant and are known as mucopolysaccharides. The most prominent monosaccharide is mannose-6- Review Article ALOE VERA: A SHORT REVIEW Amar Surjushe, Resham Vasani, D G Saple Abstract Aloe vera is a natural product that is now a day frequently used in the Þ eld of cosmetology. Though there are various indications for its use, controlled trials are needed to determine its real efÞ cacy. The aloe vera plant, its properties, mechanism of action and clinical uses are brieß y reviewed in this article. Key Words: Aloe vera, health and beauty, skin Indian J Dermatol 2008:53(4):163-6 Introduction The Aloe vera plant has been known and used for centuries for its health, beauty, medicinal and skin care properties. The name Aloe vera derives from the Arabic word �Alloeh� meaning �shining bitter substance,� while �vera� in Latin means �true.� 2000 years ago, the Greek scientists regarded Aloe vera as the universal panacea. The Egyptians called Aloe �the plant of immortality.� Today, the Aloe vera plant has been used for various purposes in dermatology. History Aloe vera has been used for medicinal purposes in several cultures for millennia: Greece, Egypt, India, Mexico, Japan and China.1 Egyptian queens Nefertiti and Cleopatra used it as part of their regular beauty regimes. Alexander the Great, and Christopher Columbus used it to treat soldiers� wounds. The Þ rst reference to Aloe vera in English was a translation by John Goodyew in A.D. 1655 of Dioscorides� Medical treatise De Materia Medica.2 By the early 1800s, Aloe vera was in use as a laxative in the United States, but in the mid-1930s, a turning point occurred when it was successfully used to treat chronic and severe radiation dermatitis.2 Plant The botanical name of Aloe vera is Aloe barbadensis miller. It belongs to Asphodelaceae (Liliaceae) family, and is a shrubby or arborescent, perennial, xerophytic, succulent, pea- green color plant. It grows mainly in the dry regions of Africa, Asia, Europe and America. In India, it is found in Rajasthan, Andhra Pradesh, Gujarat, Maharashtra and Tamil Nadu. From the Department of Dermatology, Venereology and Leprosy, Grant Medical College and Sir J J Group of Hospitals, Mumbai - 400 008 Maharashtra, India. Address for correspondence: Dr. Amar Surjushe, Department of Dermatology, Venereology and Leprosy, Grant Medical College, Gokuldas Tejpal Hospital, Mumbai - 400 008, Maharashtra, India. E-mail: dramarsurjushe@rediffmail.com [Downloaded free from http://www.e-ijd.org on Wednesday, October 06, 2010, IP: 200.3.154.74] Indian J Dermatol 2008; 53(4) 164 phosphate, and the most common polysaccharides are called glucomannans [beta-(1,4)-acetylated mannan]. Acemannan, a prominent glucomannan has also been found. Recently, a glycoprotein with antiallergic properties, called alprogen and novel anti-inß ammatory compound, C-glucosyl chromone, has been isolated from Aloe vera gel.7,8 5. Anthraquinones: It provides 12 anthraquinones, which are phenolic compounds traditionally known as laxatives. Aloin and emodin act as analgesics, antibacterials and antivirals. 6. Fatty acids: It provides 4 plant steroids; cholesterol, campesterol, β-sisosterol and lupeol. All these have anti- inß ammatory action and lupeol also possesses antiseptic and analgesic properties. 7. Hormones: Auxins and gibberellins that help in wound healing and have anti-inß ammatory action. 8. Others: It provides 20 of the 22 human required amino acids and 7 of the 8 essential amino acids. It also contains salicylic acid that possesses anti-inß ammatory and antibacterial properties. Lignin, an inert substance, when included in topical preparations, enhances penetrative effect of the other ingredients into the skin. Saponins that are the soapy substances form about 3% of the gel and have cleansing and antiseptic properties. Mechanism of actions 1. Healing properties: Glucomannan, a mannose-rich polysaccharide, and gibberellin, a growth hormone, interacts with growth factor receptors on the Þ broblast, thereby stimulating its activity and proliferation, which in turn signiÞ cantly increases collagen synthesis after topical and oral Aloe vera.9 Aloe gel not only increased collagen content of the wound but also changed collagen composition (more type III) and increased the degree of collagen cross linking. Due to this, it accelerated wound contraction and increased the breaking strength of resulting scar tissue.10 An increased synthesis of hyaluronic acid and dermatan sulfate in the granulation tissue of a healing wound following oral or topical treatment has been reported.11 2. Effects on skin exposure to UV and gamma radiation: Aloe vera gel has been reported to have a protective effect against radiation damage to the skin.12,13 Exact role is not known, but following the administration of aloe vera gel, an antioxidant protein, metallothionein, is generated in the skin, which scavenges hydroxyl radicals and prevents suppression of superoxide dismutase and glutathione peroxidase in the skin. It reduces the production and release of skin keratinocyte-derived immunosuppressive cytokines such as interleukin-10 (IL-10) and hence prevents UV-induced suppression of delayed type hypersensitivity.14 3. Anti-infl ammatory action: Aloe vera inhibits the cyclooxygenase pathway and reduces prostaglandin E2 production from arachidonic acid. Recently, the novel anti-inß ammatory compound called C-glucosyl chromone was isolated from gel extracts.8 4. Effects on the immune system: Alprogen inhibit calcium inß ux into mast cells, thereby inhibiting the antigen- antibody-mediated release of histamine and leukotriene from mast cells.7 In a study on mice that had previously been implanted with murine sarcoma cells, acemannan stimulates the synthesis and release of interleukin-1 (IL-1) and tumor necrosis factor from macrophages in mice, which in turn initiated an immune attack that resulted in necrosis and regression of the cancerous cells.15 Several low-molecular-weight compounds are also capable of inhibiting the release of reactive oxygen free radicals from activated human neutrophils.16 5. Laxative effects: Anthraquinones present in latex are a potent laxative. It increases intestinal water content, stimulates mucus secretion and increases intestinal peristalsis.17 6. Antiviral and antitumor activity: These actions may be due to indirect or direct effects. Indirect effect is due to stimulation of the immune system and direct effect is due to anthraquinones. The anthraquinone aloin inactivates various enveloped viruses such as herpes simplex, varicella zoster and inß uenza.18 In recent studies, a polysaccharide fraction has shown to inhibit the binding of benzopyrene to primary rat hepatocytes, thereby preventing the formation of potentially cancer- initiating benzopyrene-DNA adducts. An induction of glutathione S-transferase and an inhibition of the tumor- promoting effects of phorbol myristic acetate has also been reported which suggest a possible beneÞ t of using aloe gel in cancer chemoprevention.19,20 7. Moisturizing and anti-aging effect: Mucopolysaccharides help in binding moisture into the skin. Aloe stimulates Þ broblast which produces the collagen and elastin Þ bers making the skin more elastic and less wrinkled. It also has cohesive effects on the superÞ cial ß aking epidermal cells by sticking them together, which softens the skin. The amino acids also soften hardened skin cells and zinc acts as an astringent to tighten pores. Its moisturizing effects has also been studied in treatment of dry skin associated with occupational exposure where aloe vera gel gloves improved the skin integrity, decreases appearance of Þ ne wrinkle and decreases erythema.21 It also has anti-acne effect. 8. Antiseptic effect: Aloe vera contains 6 antiseptic agents: Lupeol, salicylic acid, urea nitrogen, cinnamonic acid, phenols and sulfur. They all have inhibitory action on fungi, bacteria and viruses. Surjushe, et al.: Aloe vera [Downloaded free from http://www.e-ijd.org on Wednesday, October 06, 2010, IP: 200.3.154.74] Indian J Dermatol 2008; 53(4) 165 Clinical uses: The clinical use of aloe vera is supported mostly by anecdotal data. Though most of these uses are interesting, controlled trials are essential to determine its effectiveness in all the following diseases.22,23 A. Uses based on scientifi c evidence: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Conditions: Seborrheic dermatitis,24 psoriasis vulgaris,25,26 genital herpes,27,28 skin burns,5,29 diabetes (type 2),30 HIV infection,31 cancer prevention,32,33 ulcerative colitis34 wound healing (results of aloe on wound healing are mixed with some studies reporting positive results35 and others showing no beneÞ t36 or potential worsening37,38), pressure ulcers,36 mucositis,39 radiation dermatitis,40 acne vulgaris,41 lichen planus,42 frostbite,43 aphthous stomatitis,44 and constipation.17 B. Uses based on tradition or theory: The below uses are based on tradition or scientiÞ c theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Conditions: Alopecia, bacterial and fungal skin infections, chronic leg wounds, parasitic infections, systemic lupus erythematosus, arthritis and tic douloureux. Side effects Topical: It may cause redness, burning, stinging sensation and rarely generalized dermatitis in sensitive individuals. Allergic reactions are mostly due to anthraquinones, such as aloin and barbaloin. It is best to apply it to a small area Þ rst to test for possible allergic reaction. Oral: Abdominal cramps, diarrhea, red urine, hepatitis, dependency or worsening of constipation. Prolonged use has been reported to increase the risk of colorectal cancer. Laxative effect may cause electrolyte imbalances (low potassium levels). Contraindication: Contraindicated in cases of known allergy to plants in the Liliaceae family. Pregnancy and breastfeeding: Oral aloe is not recommended during pregnancy due to theoretical stimulation of uterine contractions, and in breastfeeding mothers, it may sometime causes gastrointestinal distress in the nursing infant. Interactions: Application of aloe to skin may increase the absorption of steroid creams such as hydrocortisone. It reduces the effectiveness and may increases the adverse effects of digoxin and digitoxin, due to its potassium lowering effect. Combined use of Aloe vera and furosemide may increase the risk of potassium depletion. It decreases the blood sugar levels and thus may interact with oral hypoglycemic drugs and insulin. Thus, though Aloe vera has wide spectrum of the properties and uses, some of them could be myths and some of them could be real magic. In future, controlled studies are required to prove the effectiveness of Aloe vera under various conditions. References 1. Marshall JM. Aloe vera gel: What is the evidence? Pharma Jr 1990;24:360-2. 2. Davis RH. Aloe vera: A scientiÞ c approach. New York: Vantage Press. 3. Tyler V. The honest herbal: A sensible guide to the use of herbs and related remedies. 3rd ed. Binghamton, New York: Pharmaceutical Products Press; 1993. 4. Atherton P. Aloe vera revisited. Br J Phytother 1998;4:76-83. 5. Shelton M. Aloe vera, its chemical and therapeutic properties. Int J Dermatol 1991;30:679-83. 6. Atherton P. The essential Aloe vera: The actions and the evidence. 2nd ed. 1997. 7. Ro JY, Lee B, Kim JY, Chung Y, Chung MH, Lee SK, et al. Inhibitory mechanism of aloe single component (Alprogen) on mediator release in guinea pig lung mast cells activated with speciÞ c antigen-antibody reactions. J Pharmacol Exp Ther 2000;292:114-21. 8. Hutter JA, Salmon M, Stavinoha WB, Satsangi N, Williams RF, Streeper RT, et al. Anti-inß ammatory C-glucosyl chromone from Aloe barbadensis. J Nat Prod 1996;59:541-3. 9. Chithra R Sajithlal GB, Chandrakasan G. Inß uence of aloe vera on collagen characteristics in healing dermal wounds in rats. Mol Cell Biochem 1998;181:71-6. 10. Heggers J, Kucukcelebi A, Listengarten D, Stabenau J, Ko F, Broemeling LD, et al. BeneÞ cial effect of aloe on wound healing in an excisional wound model. J Altern Complement Med 1996;2:271-7. 11. Chithra P, Sajithlal G, Chandrakasan G. Inß uence of aloe vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats. J Ethnopharmacol 1998;59:179-86. 12. Roberts DB, Travis EL. Acemannan-containing wound dressing gel reduces radiation-induced skin reactions in C3H mice. Int J Radiat Oncol Biol Phys 1995;32:1047-52. 13. Sato Y, Ohta S, Shinoda M. Studies on chemical protectors against radiation XXXI: Protective effects of Aloe arborescens on skin injury induced by x-irradiation. Yakugaku Zasshi 1990;110:876-84. 14. Byeon S, Pelley R, Ullrich SE, Waller TA, Bucana CD, Strickland FM. Aloe barbadensis extracts reduce the production of interleukin-10 after exposure to ultraviolet radiation. J Invest Dermtol 1988;110:811-7. 15. Peng SY, Norman J, Curtin G, Corrier D, McDaniel HR, Busbee D. Decreased mortality of Norman murine sarcoma in mice treated with the immunomodulator, acemannon. Mol Biother 1991;3:79-87. 16. Hart LA, Nibbering PH, van den Barselaar MT, van Dijk H, van den Burg AJ, Labadie RP. Effects of low molecular constituents from aloe vera gel on oxidative metabolism and cytotoxic and bactericidal activities of human neutrophils. Int J Immunopharmacol 1990;12:427-34. 17. Ishii Y, Tanizawa H, Takino Y. Studies of aloe. V: Mechanism of cathartic effect. Biol Pharm Bull 1994;17:651-3. 18. Sydiskis RJ, Owen DG, Lohr JL, Rosler KH, Blomster RN. Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother 1991;35:2463-6. Surjushe, et al.: Aloe vera [Downloaded free from http://www.e-ijd.org on Wednesday, October 06, 2010, IP: 200.3.154.74] Indian J Dermatol 2008; 53(4) 166 Received: July, 2007. Accepted: March, 2008. Source of Support: Nil, Conß ict of Interest: Nil. 19. Kim HS, Lee BM. Inhibition of benzo [a] pyrene-DNA adduct formation by aloe barbadensis Miller. Carcinogenesis 1997;18:771-6. 20. Kim HS, Kacew S, Lee BM. In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis Miller, Lentinus edodes, Ganoderma lucidum, and Coriolus vesicolor). Carcinogenesis 1999;20:1637-40. 21. West DP, Zhu YF. Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure. Am J Infect Control 2003;31:40-2. 22. Zawahry ME, Hegazy MR, Helal M. Use of aloe in treating leg ulcers and dermatoses. Int J Dermatol 1973;12:68-73. 23. Ernst E, Fugh-Berman A. Methodological considerations in testing the efÞ cacy of complementary/alternative treatments (CATs). Int J Alt Comp Med 1998;16:8-10. 24. Vardy AD, Cohen AD, Tchetov T. A double-blind, placebo-controlled trial of Aloe vera (A. barbadensis) emulsion in the treatment of seborrheic dermatitis. J Derm Treatment 1999;10:7-11. 25. Paulsen E, Korsholm L, Brandrup F. A double-blind, placebo- controlled study of a commercial Aloe vera gel in the treatment of slight to moderate psoriasis vulgaris. J Eur Acad Dermatol Venereol 2005;19:326�31. 26. Syed TA, Ahmad SA, Holt AH, Ahmad SH, Afzal M. Management of psoriasis with Aloe vera extract in a hydrophilic cream: A placebo-controlled, double-blind study. Trop Med Int Health 1996;1:505-9. 27. Syed TA, Afzal M, Ashfaq AS. Management of genital herpes in men with 0.5% Aloe vera extract in a hydrophilic cream: A placebo-controlled double-blind study. J Derm Treatment 1997;8:99-102. 28. Syed TA, Cheema KM, Ahmad SA, Ashfaq A. 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Aloe vera dermal wound gel is associated with a delay in wound healing. Obstet Gynecol 1991;78:115-7. 39. Su K, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J, et al. Phase II double-blind randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms. Int J Radiat Oncol Biol Phys 2004;60:71-7. 40. Bosley C, Smith J, Baratti P. A phase III trial comparing an anionic phospholipid-based (APP) cream and aloe vera-based gel in the prevention and treatment of radiation dermatitis. Int J Radiat Oncol Biol Phys 2003;57:S4-38. 41. Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. Med J Aust 1990;153:455-8. 42. Hayes SM. Lichen planus: A report of successful treatment with aloe. Gen Dent 1999;47:268-72. 43. McCauley RL, Heggers JP, Robson MC. Frostbite: Methods to minimize tissue loss. Postgrad Med 1990;88:67-8,73-7. 44. Garnick JJ, Singh B, Winkley G. Effectiveness of a medicament containing silicon dioxide, aloe, and allantoin on aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:550-6. Surjushe, et al.: Aloe vera [Downloaded free from http://www.e-ijd.org on Wednesday, October 06, 2010, IP: 200.3.154.74]