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An updated review of aloe vera By Ray Henny Terry Corporation, Indian Harbour Beach, FL, Llc “cure-all” of many diseases, ailments, or afflic- tions, have caused some concern as to where, when, and how this plant works. The purpose of this paper is to update what is happening with the aloe vera plant in respect to history, current findings of the medical industry, identification of some of the compounds, commercial applica tions of extracts, safety data, and efficacy of extracts in cosmetics. Medicinal values of aloe Grosourdy states that Lemaire found that when the crude crushed leaves were applied to com- mon burns severe pain immediately stopped and the usual lesion did not develop. Asenjo briefly summarized the value of the aloe plant in the treatment of diseases of the chest, wounds, ringworm, roundworm, and as a purgative? In South America, it was used in the treatment of common burns, In more recent history, Bames indicated that the sate of healing of abrasions of human skin was definitely improved by the ap- plication of the fresh aloe vera leaf? Bovik de- scribed aloe vera extract as a yellowish, viscous, watery gel secreted from the leaves of the aloe vera plants He also reported that in South and Central America the Indians have used aloe vera gel for centuries for treating burns, kidney and bladder infections, prostatitis,” dysentery, stomach and intestinal disorders, and for im creasing longevity and sexual prowess. He con: cluded by describing the use of aloe vera fol- lowing periodontal surgery and suggested that aloe vera gel may have more use in dental therapeuties. Berner described the use of aloe vera by natives in tropical areas for treatment of skin diseases, wounds, bums, eye afflictions, and intemal disorders Chopia reported the use of aloe vera in India, under the name of Aloe Vera Musabar, as an’ anti-inflammatory agent! Stuart and Cole and Chen described the use of aloe vera in China for treatment of such things as sinusitis, high fever, skin eruptions, dental disorders, and canvolsions."* In the medicinal literature available from the United States, the use of aloe has been de- scribed mainly in the treatment of burns fol- lowing radiation therapy. Collins and Collins presented the first reported case of the use of aloe vera in the treatment of a patient suffering from severe x-ray dermatitis of the forehead At the end of five weeks the dermatitis had com- pletely healed. The area showed complete re~ generation of the skin on the scalp and forehead, new hair growth, restoration of sensation, and no searring. Wright, Loverman, and Fine and Brown published clinical reports on the use of aloe vera gel in the treatment of sequelae to radiation therapy.'*# In all cases, the results fa- vored the use of aloe vera gel. From a cosmetic point of view st must be noted that Wright found the texture of the skin to be improved in all cases—a smoothing and softening of the affected skin, Maadeville’s study involved an os- teroradioncerosis following radiation therapy for squamous cell epithelioma of the tongue. When fresh aloe vera gel was applied, relief from pain was immediate and the ulcer grew smaller. Rowe individually and Rowe and coworkers used aloe vera gel in experimentally produced third-degree x-ray reactions on the skin of white rats, Treatment showed a definite increase in healing. Crewe used aloes as both ointments and powders to treat conditions such as palmar eczema, ulcers on amputation stumps, ulcers of advanced mammary carcinoma, poison ivy, and burns.®"* Excellent results were obtained in all cases. Crewe reported that the use of fresh aloe relieved pain, burning, and itching, had an- tiseptic action, and stimulated rapid granulation and formation of new tissue so that denuded areas seemed to heal faster than when other agents were used. Lushbaugh and Hale, in treating artificially produced acute radioder- matitis with aloe vera, showed that healing oc- curred in half the time required for the un- ‘treated control lesions." Around the world, various applications have been found that show great promise. Blitz and coworkers treated 18 patients for Duodenal ul- cers with 17 recovering completely and only one showing no improvement.!* Mortada and co- workers at the Cairo University, treated corneal ulcers with aloe extracts and found the treated eyes showed mote healing, less cellular reac- tion, and fewer signs of irritation.” Logai used subeutaneous injections of aloe extract along with other treatments for traumatic hemorrhages into the vitreous body.” The aloe gave better therapeutic effect in cases where other methods of treatment were ineffective. Fujita and cowor- kers found, as pharmacological evidence for the anti-inflammatory action of aloe, evidence indi- cating that aloe extract contains brandykininase activity" Brasher and coworkers studied the effects of three therapeutic agents on mono- layers of epithelial and fibroblast cell cultures. The three drugs used were prednisolone (3 corticosteroid), indomethacin (a non-steroid i-inflammatory drug), and aloe vera, The three drugs were applied on tissue culture cells in various dilutions for periods of 24, 48, and 72 hours. There was complete toxicity of all the cells when the most concentrated solutions of the test agents were used, but aloe vera, at lower dilutions, was associated with higher cell counts than the other drugs Tt was suggested that solutions of aloe vera might be incorporated into periodontal dress- ings. Grammer incorporated aloe vera into two commercially available periodontal dressings. The dressings were placed into cell cultivations of epithelial and fibroblast cell lines. He discov- ered that higher dilutions of aloe vera seemed to stimulate the growth rate of tissue calture cells when compared to the untreated controls.*® Payne, in his topical use of aloe vera following periodontal flap surgery, found that post- operative pain was reduced more than with the normal saline control and swelling of tissues treated with aloe vera was not as marked as the swelling of the control tissues Also, the pres- ence of a greater number of inflammatory cells and dilated vessels in the control tissue speci- mens, as compared to gingiva treated with aloe, vera, may indicate aloe vera increases the rate of healing of periodontal surgical wounds. in an effort to determine if certain drugs exert some of their pharmacological effects by stimulating postaglandin synthetase, Collier and coworkers found aloes, tyramine, ethanol, and quipazine produced a dose-related increase in resting the tone of the isolated fundus of the rat stomach* This increase occurred at concen- trations comparable to those effective in stimulating BSV prostaglandin synthetase. Noskoy treated 50 patients with first-third stages of parodontosis by means of aloe extract injections. The results yielded a satisfactory effect only in the first-second stages of the dis- ease. The content of calcium, elevated in the blood serum in parodontosis, normalizes in the treatment with aloe extracts. Savitsky reported that aloe and an extract of bioset manifest a reg- ular activating effect on aspartate-amino- transferase and alanine-aminotransferase fune~ tion.” The nature of this effect an the activity of each enzyme in various tissues varies both as 1 the degree and time of the alterations and as to their trend—i.e., there is a pronounced tissue specificity. The regular effect of both tissue preparations of the amino group transfer process 4s one of the central links in the mechanism of their action on the metabolista and general state of the organ El Zawahry and coworkers evaluated aloe vera gel in the treatment of chronic ulcers and certain other dermatoses in men2* The report deals with its uses locally in chronic leg ulcers, sehorthea, acne vulgaris, alopecia (hair fall), and alopecia areata. The results proved to have a stimulating effect on the healing of chronic leg ulcers. Aloe appears to stimulate hair growth and drying of seborrheic skin’, El Zawahry be- lieved the active principle for promoting healing is the mucopoly-saccharides which are present in high concentration in the aloe gel and this may be aided by enzymatic removal of necrotic tissue. Figure 1 shows a leg ulcer of a 16 year old girl before treatment. Figure 2 shows the Figure! ‘ulcer after 30 days of treatment with topically applied aloe vera gel, plus an internal dosage of aloe vera gel. Figure 3 shows the ulcer after 60 days of continued treatment, and figure 4 shows the result after 90 days of treatment. This is the type of response that people from around the world have been talking about for years. The Figure 2 em Figure 4 only conclusion that can be drawn from the evi- dence is that aloe works. Components of aloe The voluminous medical information sup- porting the effectiveness of aloe in gel or various extracts that is now available to research per- sonnel leads one to the question: “What compo- nent or components are responsible for the overall effectiveness?” ‘The main ingredients of aloe, as described by Chopia and Ghosh, are aloin, emodin, chryso- Phanic acid, resin, gum, and traces of a volatile and non-volatile oil.2* Since this original work was completed, there has been much published about the components of the aloe plant.2™* The following chemical components have been reported to be present in aloe: aloin; aloe emo- din; aloetic acid; homonataloin; alvesin; aloe- sone; emodin; chrysamminie acid; chrysophanie acid; apoise; beta barbaloin; isobarbaloin; O- glycosides; galacturonic acid; calcium oxalate; choline; choline salicylate; saponins; uronic acid; sugars, simple and hydrolyzable; complex mucopolysaccharides; 2'-O-p-coumaroylaloesin (D; 2-O-feruloylaloesin (1); protein containing 18 amino acids; 7-hydroxchromone; 8-C- glucosyl-7 hydroxychromone; myrcene; limo- nene; coniferyl alcohol; O-xylotocopherol; 2- methyl-2-phytyl-6-chromanol; peteroylglutamie acid; glucosamines; hexuronic acid; casan- thranol I; casanthranol 14; sapogenin glycosides; hecogernins; pentahydroxylflavones; enzymes of catalase, amylase, oxidase, cellulose; and al- liinase, The minerals (fig. 5) are also present. It must be pointed out that all species do not con- tain the same amount or the same components, and the seasonal climate causes variations in the anthraquinones present. The work done to isolate the above compo- nents and the knowledge that none of the chemicals individually can give the results found when using aloe tend to indicate a syner- aistie effect among one or more components. It has been indicated that the mucopolysac- charides are responsible for the healing effects. This relationship is backed up by re Evidence in literature eliminates vitamins, urea, and tannins as possible agents responsible for the healing effects.'* Can the benefits derived be a synergistic effect from the mucopolysac- charides, sulfur derivatives, and nitrogen com- pounds present? Only further research will re- solve this question. Another area of interest to research personnel working with natural plants is determining whether the plant or its extracts have any bacte- rial or fungicidal properties. In the case of aloe, Gottshall tested 28 different species against Mycobacterium tuberculosis, Staphlococcus au- reus, and E. colis* Aloe chinensis was active against the Mycobacterium tuberculosis. George and Pandalai found that an aqueous extract of aloe littoralis inhibited the growth of both Staphylococcus aureus and E, coli while an al- coholic extract of the same species exhibited no measurable inhibition." Fly, using aloe bar- badensis and aloe vera against Staphylococcus aureus and E. coli, reported that neither the gel portion nor the leafy portion had any antibiotic effects. Richards, in testing the mascerated gel of aloe vera (fig. 6), found a decrease in all cases but the Candida albicans which shows a 108% increase* There is not enough evidence pre- sented to draw any conclusions as to the effec- tiveness of aloe in this experiment. Further work is indicated. Sage has shown different results when using stabilized aloe gel against Candida albicans. The results show a 91% decrease in the organism. In general, it seems that if aloe is to be effective against any organisms, it must be used at a concentration in excess of 90%. Current cosmetic applications There are many cosmetics on the market today which use aloe extracts in concentrations vary- ing from 1% to 98%. The aloe extracts have found a place in certain pharmaceutical applica- tions as well. The use of aloe in cosmetics is not new, but the acceptance of its emollient, mois- turizing, and healing properties seems to be documented in reputable scientific journals. Safety data on the aloe vera lipo-quinone #10113 and aloe vera aqueous extract #10209 have been accumulated. The following tests were performed: © Primary skin irritation © Draize Eye irritation © Single level acute LDso ¢, Guinea pig sensitization The results are: @ Aloe vera lipo-quinone, according to Kay and Calandra, is practically’ non-irritating when applied to the eye. @ Aloe vera aqueous extract, according to Kay and Calandra, is minimally irritating when applied to the eye. © Aloe vera lipo-quinone and aloe vera aqueous extracts, when evaluated according to Hodge and Sterner, are relatively harmless when dosed orally. © Aloe vera lipo-quinone and aloe vera aqueous extracts, when evaluated for skin sensitization in accordance with the Draize Sensitization Test Procedure, did not exhibit any positive reactions for skin sensitization. Aloe vera extracts can be considered safe when used near the eye, on the skin, or when ingested in a single dose. ‘The efficacy of aloe extracts can be shown with reference to past clinical studies as Goff and Levenstein and, later, Northway." Goff used aloe vera extract, artemisa tridentata, and several other agents to determine whether the effects of topically applied preparations on the healing of skin wounds could be measured quantitatively, The comparison of the strength of the wounds treated with aloe vera extract, the artemisa oil, and controls is shown in figure 7. Statistically’ significant differences in favor of 10 z Tensile whengrh gm. $3 > 6 f a ow wot Deys Afr Wound Inflicted Tensile strength of wounds treated with plant extracts Figure 7 aloe vera are seen at nine and fifteen days. However, 21 days after the wounds were in- flicted, the values are essentially the same. Northway used aloe vera gel in the treatment of 76 various animals with mixed infections. No controls were used so the results cannot lead to definite conclusions. The results ranged from “excellent” to “no response.” The overall effect is one of improvement, Conclusions Many different species of aloe possess heal- ing, moisturizing, and emollient properties. Identification of aloe’s components is needed to further establish what the effective component or components are. Clinical studies presented show effectiveness of aloe extracts, Aloe extracts are effective in cosmetic and pharmaceutical formulations. Reforonces 1. d. Renato de Grosourdy, BI medice botanic ctl, 3, 24 306-311, Pore (186) 2. Conrads F. Aveo, Apuntesocerco delas plantas medicinales tbe Poarto ical, Revs Agr, 28, 741-748, Puerto Rico (1987) 2. T.C. Bornes, The beaing action of extracts of alee vera lef on ‘brosion of human sin, Am. Batony, 34, 597 (1947), 4. £6. Bow, Aloe vero: Poracee or old wives toes? Texos Den! 384, Tet6 968) 5, U Berner t 6. RM Chopia, Indigenous drugs of Indo, The Art Pres, Cok cum, 1983, pp. 57-58 7. GA. Swany Chinese materia medica, Am. Pretby, Pr Shanghsi 1911, pp. 29-20 8. HON. Cola and'k. K. Chen, Alo vera in arentel dermatology, ‘Arch, Dermatol. Syphi, 47, 280-255 (1943) 9 CE Coline and €. Cols, Roenrgan dermatitis treated wih fresh whola loaf of oloe vera, Am J. Roamtger, 38, 1402 935) 10. C.. Wiigh, Aloe vera inthe westmant of xantgen ulcers ond telongiecoas, J, Am. ed. Asn, 103, 1963-1964 (196), 11, A.B Loverman, Leaf of aloe vera in reatment of roentgen roy sicara, veh, Dermota. Syphi., 36, 838-043 (1997) 12, M. Fine ond S, Brown, Culvaton and cinical oppicaton of lle vera leet, Rodiclogy, 1, 725-736 (1998) 13, FB. Mandevile, Aloe vera in wectment of radiation vers of mucous membranes, Raclogy, 32, 598-599 (1939) 14, TD. Rowe Effect of fash oloe vera gel in the vectment of ‘hed degree roentgen reaction of whte rata, J. Am- Pharm, ‘Asn, 29, 248-550 (1940) 15, T.D. Rowe, 8.K, Level nd LM. Poss, Further observations con the use of clce vera leaf in the rectinent of Ned degree ‘ray rections, J. fe. Phar. 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