THE LIBRARY

Editorial commentary and notes are in italics preceding, and also sometimes within, the abstracts.

General history

A nice little history of aloe’s uses follows in this lead abstract. 

The Aloe vera phenomenon: a review of the properties and modern uses of the leaf parenchyma gel.

Grindlay D, Reynolds T.

The mucilaginous gel from the parenchymatous cells in the leaf pulp of Aloe vera has been used since early times for a host of curative purposes. This gel should be distinguished clearly from the bitter yellow exudate originating from the bundle sheath cells, which is used for its purgative effects. Aloe vera gel has come to play a prominent role as a contemporary folk remedy, and numerous optimistic, and in some cases extravagant, claims have been made for its medicinal properties. Modern clinical use of the gel began in the 1930s, with reports of successful treatment of X-ray and radium burns, which led to further experimental studies using laboratory animals in the following decades. The reports of these experiments and the numerous favourable case histories did not give conclusive evidence, since although positive results were usually described, much of the work suffered from poor experimental design and insufficiently large test samples. In addition some conflicting or inconsistent results were obtained. With the recent resurgence of interest in Aloe vera gel, however, new experimental work has indicated the possibility of distinct physiological effects. Chemical analysis has shown the gel to contain various carbohydrate polymers, notably either glucomannans or pectic acid, along with a range of other organic and inorganic components. Although many physiological properties of the gel have been described, there is no certain correlation between these and the identified gel components.
Although in 1986 the last sentence was for the most part true, what follows is a mountain of evidence to the contrary that accrues in an accelerating rate over a relatively short time!

 
Aloe vera: a systematic review of its clinical effectiveness.

Vogler BK, Ernst E.

Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter.

BACKGROUND: The use of aloe vera is being promoted for a large variety of conditions. Often general practitioners seem to know less than their patients about its alleged benefits. AIM: To define the clinical effectiveness of aloe vera, a popular herbal remedy in the United Kingdom. METHOD: Four independent literature searches were conducted in MEDLINE, EMBASE, Biosis, and the Cochrane Library. Only controlled clinical trials (on any indication) were included. There were no restrictions on the language of publication. All trials were read by both authors and data were extracted in a standardized, pre-defined manner. RESULTS: Ten studies were located. They suggest that oral administration of aloe vera 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. There are major caveats associated with all of these statements. CONCLUSION: Even though there are some promising results, clinical effectiveness of oral or topical aloe vera is not sufficiently defined at present.

Jump ahead in time and instead of the statements of our ignorance, the complexity and properties of many of the constituent compounds in aloe are compiled in the studies reported in the next abstract in 2003.  Anti-inflammatory, antioxidant, and tumor suppressive properties are explored.

 
[Anti-inflammatory constituents, aloesin and aloemannan in Aloe species and effects of tanshinon VI in Salvia miltiorrhiza on heart]

[Abstract in Japanese]

Yagi A, Takeo S.

Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985 Gakuen-cho, Fukuyama 729-0292, Japan. yagi@fupharm.fukuyama-u.ac.jp

Cinnamoyl, p-coumaroyl, feruloyl, caffeoyl aloesin, and related compounds were isolated from Aloe species. The antiinflammatory and antioxidative activities of these compounds were examined based on the structure-activity relationship. It was suggested that the bioactivities may link to acyl ester groups in aloesin, together with those of aloesin-related compounds. However, investigations using the contact hypersensitivity response indicated a preventive effect of aloesin on the UV-B-induced immune suppression. Furthermore, aloesin inhibited tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human melanocyte cell lysates. These results show that aloesin prevents not only UV-B-induced immune suppression, but also could be a positive pigment-altering agent for cosmetic application. In preclinical study, aloe extract was investigated using phagocytosis and nitroblue tetrazolium chloride (NBT) reduction in adult bronchial asthma, and high molecular-weight materials, such as polysaccharide and glycoprotein fractions, were identified as active ingredients. The neutral polysaccharides, aloemannan and acemannan showed antitumor, antiinflammatory and immunosuppressive activities, and glycoprotein fractions with bradykinin-degrading and cell proliferation-stimulating activities were identified from the nondialysate fraction of the gel part of Aloe species. Verectin fractionated from Aloe vera gel was examined biochemically and immunochemically, and verectin antibody was used in the appraisal of commercial Aloe vera gel products. It was reported that aloesin stimulates the proliferation of cultured human hepatoma SK-Hep 1 cells. Thus aloesin, related compounds, and high molecular-weight materials, such as aloemannan and verectin, may act in concert to exert therapeutic properties for wounds, burns and inflammation. The biodisposition [Editor’s note:  where it went] of fluoresceinylisothiocyanate (FITC)--labeled aloemannan (FITC-AM) with the homogenate from some organs in mice was demonstrated, and FITC-AM was metabolized to a smaller molecule (MW 3000) by the large intestinal microflora in feces. The modified aloe polysaccharide (MW: 80000) with cellulase under restricted conditions, immunologically stimulated the recovery of UV-B-induced tissue in jury. Thus the modified polysaccharides of aloemannan, together with acemannan (MW: about 600000), are expected to participate in biological activity following oral administration. [Editor’s note:  abstract truncated at this point due to its continuation with compounds from another herbal medicinal plant)]
This next fairly recent abstract generally sets the stage for what is to come.

Aloe vera leaf gel: a review update.

Reynolds T, Dweck AC.

Jodrell Laboratory, Royal Botanic Gardens, Kew, Richmond, Surrey, UK.

Research since the 1986 review has largely upheld the therapeutic claims made in the earlier papers and indeed extended them into other areas. Treatment of inflammation is still the key effect for most types of healing but it is now realized that this is a complex process and that many of its constituent processes may be addressed in different ways by different gel components. A common theme running through much recent research is the immunomodulatory properties of the gel polysaccharides, especially the acetylated mannans from Aloe vera, which are now a proprietary substance covered by many patents. There have also been, however, persistent reports of active glycoprotein fractions from both Aloe vera and Aloe arborescens. There are also cautionary investigations warning of possible allergic effects on some patients. Reports also describe antidiabetic, anticancer and antibiotic activities, so we may expect to see a widening use of aloe gel. Several reputable suppliers produce a stabilized aloe gel for use as itself or in formulations and there may be moves towards isolating and eventually providing verified active ingredients in dosable quantities.
Wound healing
Wound healing is a real focus of medicinal applications of aloe.  There are many types of wounds and many models used to study and evaluate the effect of aloe on the wound healing process.  We have included many abstracts covering this broad topic.
Anti-inflammatory properties
More history using aloe preparations topically to treat skin inflammation; possible mechanisms explored in this, the first abstract focusing on inflammation in an experimental model of arthritis:

Aloe vera and gibberellin. Anti-inflammatory activity in diabetes.

Davis RH, Maro NP.

Aloe vera inhibits inflammation and adjuvant-induced arthritis [Editor’s note: This type of arthritis is an experimental model. A chemical from a class of chemicals called adjuvants provokes joint inflammation.  The authors' laboratory has shown that A. vera improves wound healing, which suggests that it does not act like an adrenal steroid.]  Diabetic animals were used in this study because of their poor wound healing and reduced anti-inflammatory capabilities. The anti-inflammatory activity of A. vera and gibberellin was measured in streptozotocin-induced diabetic mice by measuring the inhibition of polymorphonuclear leukocyte infiltration into a site of gelatin-induced inflammation over a dose range of 2 to 100 mg/kg. Both Aloe and gibberellin similarly inhibited inflammation in a dose-response manner. These data tend to suggest that gibberellin or a gibberellin-like substance is an active anti-inflammatory component in A. vera.
A similar study follows, corroborating the above study.

Anti-inflammatory activity of Aloe vera against a spectrum of irritants.

Davis RH, Leitner MG, Russo JM, Byrne ME.

The authors have evaluated the spectrum of anti-inflammatory activity of A. vera in a number of models of inflammation in the hind paw of the experimental rat induced by kaolin, carrageenan, albumin, dextran, gelatin, and mustard. Croton oil was used in a topical model of inflammation to determine the oral activity and time-dependent dosing of A. vera. The authors found that A. vera was active in all models of inflammation. Of the various irritants tested, A. vera was especially active against gelatin-induced and kaolin-induced edema and, in contrast, had minimal activity when tested against dextran-induced edema. Oral activity of A. vera was demonstrated to be dependent on the presence of anthraquinones. The various irritant-induced edema models provided a broad spectrum of anti-inflammatory activity for A. vera.
More on anti-inflammatory efficacy:

Processed Aloe vera administered topically inhibits inflammation.

Davis RH, Rosenthal KY, Cesario LR, Rouw GA.

Aloe vera preparations were evaluated for topical anti-inflammatory activity using the croton oil-induced edema assay. The results show that small amounts of A. vera given topically will inhibit inflammation induced by a moderate amount of irritant. In general, the decolorized Aloe was more effective than the colorized Aloe (with anthraquinone). A 47.1% inhibition of inflammation was obtained by 5% decolorized irradiated Aloe. These results may be used as a baseline to assess the biologic activity of A. vera in the treatment of inflammation by podiatric physicians.
The main point of the following abstract is “Aloe vera appears to act as a modulatory system toward wounds and inflammation and is a potentially valuable tool for managing lower extremity conditions.”

Isolation of a stimulatory system in an Aloe extract.

Davis RH, Parker WL, Samson RT, Murdoch DP.

Pennsylvania College of Podiatric Medicine, Philadelphia 19107.

The authors' previous work on a 50% ethanol extract of Aloe vera was done to evaluate anti-inflammatory activity using the croton oil-induced ear swelling assay. The anti-inflammatory activity was found in the supernatant fraction. The supernatant fraction decreased inflammation, when applied topically, by 29.2%, and the precipitate decreased inflammation by 12.1%. However, in the present work, the precipitate fraction decreased the wound diameter by an average of 47.1% (stimulatory system). Little or no wound healing activity was found in the supernatant. Aloe vera appears to act as a modulatory system toward wounds and inflammation and is a potentially valuable tool for managing lower extremity conditions.
And:

Anti-inflammatory and wound healing activity of a growth substance in Aloe vera.

Davis RH, Donato JJ, Hartman GM, Haas RC.

Department of Biomedical Sciences, Pennsylvania College of Podiatric Medicine, Philadelphia.

Aloe vera improves wound healing and inhibits inflammation. Since mannose-6-phosphate is the major sugar in the Aloe gel, the authors examined the possibility of its being an active growth substance. Mice receiving 300 mg/kg of mannose-6-phosphate had improved wound healing over saline controls. This dose also had anti-inflammatory activity. The function of mannose-6-phosphate in A. vera is discussed.
Along similar lines, Aloe vera has anti-inflammatory properties and the capacity to increase wound tensile strength, promoting healing and overcoming the negative impact of cortisone, which lowers tensile strength as it decreases inflammation.

Aloe vera, hydrocortisone, and sterol influence on wound tensile strength and anti-inflammation.

Davis RH, DiDonato JJ, Johnson RW, Stewart CB.

Pennsylvania College of Podiatric Medicine, Philadelphia.

Aloe vera at doses of 100 and 300 mg/kg daily for 4 days blocked the wound healing suppression of hydrocortisone acetate up to 100% using the wound tensile strength assay. This response was because of the growth factors present in A. vera masking the wound healing inhibitors such as sterols and certain amino acids. The sterols showed good anti-inflammatory activity (-36%) in reducing the croton oil-induced ear swelling. This activity displayed a dose-response relationship.

The next abstract illustrates a mechanism with an experimental model.  Aloe stimulates proven healing by stimulating growth of fibroblasts and macrophages (the cells involved in healing inflamed joints.

Aloe vera and the inflamed synovial pouch model.

Davis RH, Stewart GJ, Bregman PJ.

Pennsylvania College of Podiatric Medicine, Philadelphia.

Administration of air under the skin produced a pouch wall that closely resembled a synovium (joint lining) in that the inner lining was made up of macrophages and fibroblasts. Administration of 1% carrageenan directly into the 7-day-old air pouch produced an inflammation characterized by an increased number of mast cells in pouch fluid as well as an increase in wall vascularity. (Editor’s note: This model represents the lining in a joint called a synovial space, as in a knee joint, which when inflamed is called synovitis)  A punch biopsy weight of the pouch wall did not reveal an increase in 1% carrageenan-treated animals. However, a 10% Aloe vera treatment of carrageenan-inflamed synovial pouches reduced the vascularity 50% and the number of mast cells in synovial fluid 48%. The pouch wall punch biopsy weight was increased by A. vera, which was verified by histologic examination of the inner synovial lining. Aloe vera stimulated the synovial-like membrane, as evidenced by an increased number of fibroblasts, suggesting that A. vera stimulated fibroblasts for growth and repair of the synovial model. The synovial air pouch can be used to study simultaneously the acute anti-inflammatory and fibroblast stimulating activities of A. vera.
The preceding study shows how aloe stimulated the growth of fibroblasts in a model of a joint, lending insight into the mechanism of how aloe increases tensile strength in wound healing reported in the abstract above this one.

More anti-inflammatory data is found in the following abstract.

 
Aloeresin I, an anti-inflammatory 5-methylchromone from cape aloe.

Speranza G, Morelli CF, Tubaro A, Altinier G, Duri L, Manitto P.

Dipartimento di Chimica Organica e Industriale, Universita degli Studi di Milano, Italy.

A new diglucoside having a 5-methylchromone moiety was isolated from a commercial sample of Cape aloe, the dried exudate from Aloe ferox Miller, and named aloeresin I. Its structure was established as 1 on the basis of spectral and chemical evidence. Aloeresin I ( 1) (1 mumol/cm (2)) reduces in vivo the oedematous response (39 %) induced by Croton oil in the mouse ear with the same potency as aloesin, one of the most abundant Cape aloe constituents, and to a higher extent than aloeresin H ( 2). Indomethacin [Editor’s note: indomethacin is a potent nonsteroidal anti-inflammatory drug with significant risk of toxicity to liver and GI hemorrhage] (0.3 mumol/cm (2)), the reference anti-inflammatory compound, provokes 61 % oedema inhibition.
Aloeresin was 2/3 as effective as the drug used for a standard.
To determine more about how aloe promotes wound healing, read the next study.

 
The wound-healing effect of a glycoprotein fraction isolated from aloe vera.

Choi SW, Son BW, Son YS, Park YI, Lee SK, Chung MH.

Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.

BACKGROUND: Aloe vera has been used as a family medicine for promoting wound healing, but it is not known which component of the plant is effective for this purpose. OBJECTIVES: To isolate and characterize the component effective in wound healing. METHODS: Chromatography, electrophoresis and spectroscopic methods were used. The cell-proliferation activity of each component isolated was measured by a [3H]thymidine uptake assay. The cell-proliferation activity of the effective component was tested on a three-dimensional raft culture (cell culture technique by which artificial epidermis is made from keratinocytes). The effect of the active component on cell migration and wound healing was observed on a monolayer of human keratinocytes and in hairless mice. RESULTS: A glycoprotein fraction was isolated and named G1G1M1DI2. It showed a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, with an apparent molecular weight of about 5.5 kDa. It exhibited significant [3H]thymidine uptake in squamous cell carcinoma cells. The effect of G1G1M1DI2 on cell migration was confirmed by accelerated wound healing on a monolayer of human keratinocytes. When this fraction was tested on a raft culture, it stimulated the formation of epidermal tissue. Furthermore, proliferation markers (epidermal growth factor receptor, fibronectin receptor, fibronectin, keratin 5/14 and keratin 1/10) were markedly expressed at the immunohistochemical level. The glycoprotein fraction enhanced wound healing in hairless mice by day 8 after injury, with significant cell proliferation. CONCLUSIONS: It is considered that this glycoprotein fraction is involved in the wound-healing effect of aloe vera via cell proliferation and migration.
In frostbite, along with other modalities, aloe helps prevent tissue loss.

Frostbite. Methods to minimize tissue loss.

McCauley RL, Heggers JP, Robson MC.

Department of Surgery, University of Texas Medical School, Galveston.

If frostbite is to be treated successfully, direct and indirect effects of injury must be understood. Rapid rewarming helps to preserve tissue by limiting the amount of direct cellular injury. Selective management of blisters helps protect the subdermal plexus, and application of Aloe vera cream (e.g., Dermaide Aloe Cream) combats the local vasoconstrictive effects of thromboxane. Oral administration of ibuprofen decreases systemic levels of thromboxane.
Another abstract regarding aloe’s efficacy in the treatment of frostbite.

Treatment of experimental frostbite with pentoxifylline and aloe vera cream.

Miller MB, Koltai PJ.

Division of Otolaryngology, Albany (NY) Medical College, USA.

OBJECTIVE: To compare the therapeutic effects of systemic pentoxifylline and topical aloe vera cream in the treatment of frostbite. DESIGN: The frostbitten ears of 10 New Zealand white rabbits were assigned to one of four treatment groups: untreated controls, those treated with aloe vera cream, those treated with pentoxifylline, and those treated with aloe vera cream and pentoxifylline. MAIN OUTCOME MEASURES: Tissue survival was calculated as the percent of total frostbite area that remained after 2 weeks. RESULTS: The control group had a 6% tissue survival. Tissue survival was notably improved with pentoxifylline (20%), better with aloe vera cream (24%), and the best with the combination therapy (30%). CONCLUSION: Pentoxifylline is as effective as aloe vera cream in improving tissue survival after frostbite injury.
Frostbite treatment efficacy of aloe follows in a protocol in combination with other substances. This next abstract shows the synergy achieved, with emphasis on the thromboxane inhibitors, of which aloe is one of two.

Experimental and clinical observations on frostbite.

Heggers JP, Robson MC, Manavalen K, Weingarten MD, Carethers JM, Boertman JA, Smith DJ Jr, Sachs RJ.

Experimental ischemia by the classic frostbite rabbit ear model clearly defined the role of thromboxane as a mediator of progressive dermal ischemia in frostbite injuries. The therapeutic groups consisted of the antiprostanoids, methylprednisolone, and aspirin combined with anti-thromboxane agents Aloe vera and methimazole, while the control group received no therapy. Survival was measured by planimetry for all groups. No tissue survival was evident in the frostbite control group. Methimazole treatment allowed 34.3% survival, Aloe vera 28.2% survival, aspirin 22.5% survival, and methylprednisolone 17.5% survival. The data compare the results of a modified frostbite protocol using ibuprofen with therapeutic modalities used by other clinical services. Of 154 patients treated for frostbite from 1982 to 1985, 56 were treated with our frostbite protocol; 98 were treated with other modalities. Of the 56 protocol patients, 18 suffered 1st degree frostbite, 25, 2nd degree frostbite, and 13, 3rd degree frostbite. For all degrees of frostbite, 67.9% healed without tissue loss, 25.0% healed with partial tissue loss, and 7% required amputation (P less than .001). Of the patients not on protocol, 11 suffered 1st degree frostbite, 51, 2nd degree frostbite, and 36, 3rd degree frostbite. Of these, 32.7% healed without tissue loss, 34.6% healed with tissue loss, and 32.7% required amputation. The morbidity of progressive dermal ischemia in frostbite may be decreased by the therapeutic use of inhibitors of the arachidonic acid cascade.
Read the numbers above several times to get the full impact of what happens when the protocol of patients incorporating aloe are compared with the controls. The conclusions are understated.   
The next abstract illustrates another situation in which thromboxane is the major factor in inducing tissue damage and shows once more the synergy when aloe and methimizole, both thromboxane inhibitors, are combined.

The role of thromboxane in experimental inadvertent intra-arterial drug injections.

Zachary LS, Smith DJ Jr, Heggers JP, Robson MC, Boertman JA, Niu XT, Schileru RE, Sacks RJ.

Inadvertent intra-arterial injection of drugs produces a well-defined clinical syndrome whose pathophysiology remains unclear. This study was designed to determine the role of the inflammatory mediator, thromboxane, in intra-arterial drug injections. The rabbit ear model, as described by Kinmonth and Sheppard, was used.[Editor’s note: this is the same model as for studying frostbite] Five of the experimental groups were treated with specific or nonspecific thromboxane blocking agents and two groups served as controls. Immunohistochemical staining of the control ears showed elevated levels of thromboxane within the first 6 hours postinjury. The specific thromboxane blocking agents, methimazole and Aloe vera, showed almost complete blockade of thromboxane production. The percentage of ear survival was significantly greater in the group treated with topical Aloe vera (p less than 0.05) and even greater survival was achieved in the combined Aloe vera/methimazole group (p less than 0.01). On the basis of these results, we have begun treatment of such injuries with specific and nonspecific thromboxane blocking agents.
A contrasting view of aloe as a topical anti-inflammatory and promoter of healing, the next study shows that the value of the gel was lower than the aqueous cream in healing the destructive effects of radiation therapy for breast cancer on the associated skin.

 
A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue.

Heggie S, Bryant GP, Tripcony L, Keller J, Rose P, Glendenning M, Heath J.

Queensland Radium Institute, Division of Oncology, Royal Brisbane Hospital, Australia. Pauline_Rose@health.qld.gov.au

The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy, including erythema, pain, itching, dry desquamation, and moist desquamation, when compared with aqueous cream. The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction, i.e., breast size, smoking habit, and one or more drainages of lymphocele after surgery, on other skin side effects. A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy, who required a course of radiation therapy using tangential fields. Patients were randomized to either topical aloe vera gel or topical aqueous cream to be applied 3 times per day throughout and for 2 weeks after completion of radiation treatment. Weekly skin assessments were performed by nursing staff. Aqueous cream was significantly better than aloe vera gel in reducing dry desquamation and pain related to treatment. Subjects with D cup or larger size breasts experienced significantly more erythema, regardless of treatment arm. For subjects who had undergone lymphocele drainage, the aloe vera group experienced significantly more pain than the aqueous cream group. Within the aqueous cream arm, smokers were significantly more likely to experience itching within the treatment field than were nonsmokers. Within the aloe vera arm, subjects who had undergone one or more lymphocele drainages after surgery were significantly more likely to experience erythema and itching within the treatment field than those who did not have drainage. In this study, aloe vera gel did not significantly reduce radiation-induced skin side effects. Aqueous cream was useful in reducing dry desquamation and pain related to radiation therapy.
Another abstract demonstrating lack of efficacy of aloe on radiation-induced skin damage:

 
Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity.

Williams MS, Burk M, Loprinzi CL, Hill M, Schomberg PJ, Nearhood K, O'Fallon JR, Laurie JA, Shanahan TG, Moore RL, Urias RE, Kuske RR, Engel RE, Eggleston WD.

Toledo Community Clinical Oncology Program, OH, USA.

PURPOSE: Considerable pilot data and clinical experience suggested that an aloe vera gel might help to prevent radiation therapy-induced dermatitis. METHODS AND MATERIALS: Two Phase III randomized trials were conducted. The first one was double blinded, utilized a placebo gel, and involved 194 women receiving breast or chest wall irradiation. The second trial randomized 108 such patients to aloe vera gel vs. no treatment. Skin dermatitis was scored weekly during both trials both by patients and by health care providers. RESULTS: Skin dermatitis scores were virtually identical on both treatment arms during both of the trials. The only toxicity from the gel was rare contact dermatitis. CONCLUSIONS: This dose and schedule of an aloe vera gel does not protect against radiation therapy-induced dermatitis.
Another study of Aloe vera and mucosal damage from radiation therapy again presents a situation in which the type of skin or, in this case, mucosal damage induced by radiation is not benefited by Aloe vera gel:

 
Phase II double-blind randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms.

Su CK, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J, Koong A, Goffinet D, Le QT.

Department of Radiation Oncology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5302, USA.

PURPOSE: In a single-institution, double-blind, prospective, randomized trial, we determined whether oral aloe vera gel can reduce radiation-induced mucositis in head-and-neck cancer patients. METHODS AND MATERIALS: We randomized 58 head-and-neck cancer patients between oral aloe vera and placebo. To be included in this Phase II protocol, patients had to be treated with radiotherapy with curative intent at Stanford University between February 1999 and March 2002. We examined patients biweekly for mucositis at 15 head-and-neck subsites and administered quality-of-life questionnaires. RESULTS: Patients in the aloe and placebo groups were statistically identical in baseline characteristics. By the end of treatment, the two groups were also statistically identical in maximal grade of toxicity, duration of Grade 2 or worse mucositis, quality-of-life scores, percentage of weight loss, use of pain medications, hydration requirement, oral infections, and prolonged radiation breaks. CONCLUSION: In our randomized study, oral aloe vera was not a beneficial adjunct to head-and-neck radiotherapy. The mean quality-of-life scores were greater in the aloe vera group, but the differences were not statistically significant. Oral aloe vera did not improve tolerance to head-and-neck radiotherapy, decrease mucositis, reduce soreness, or otherwise improve patient well-being.
Here is a contrasting view of a specific type of wound healing in which it appeared that chemically aloe prolonged wound healing in women who underwent C-section delivery.

Aloe vera dermal wound gel is associated with a delay in wound healing.

Schmidt JM, Greenspoon JS.

Department of Nursing, Women's Hospital, Los Angeles County-University of Southern California Medical Center.

We evaluated the time interval required for wound healing using a standard wound management protocol with and without aloe vera gel. Twenty-one women were studied who had wound complications requiring healing by second intention after cesarean delivery or laparotomy for gynecologic surgery. Wounds treated with standard management healed in a mean (+/- SD) time interval of 53 +/- 24 days, whereas those treated with aloe vera gel required 83 +/- 28 days (P = .003). The use of aloe vera dermal wound gel was associated with a significant delay in wound healing compared with treatment with an otherwise identical regimen that did not include aloe vera.
Note that in the above study, and perhaps in other studies, hormonal influences (such as those encountered after the stress of radiation injury) were not isolated as variables that could have influenced aloe’s efficacy.
Aloe does better with burns and frostbite than it does with radiation.

Effect of aloe vera gel to healing of burn wound a clinical and histologic study.

Visuthikosol V, Chowchuen B, Sukwanarat Y, Sriurairatana S, Boonpucknavig V.

Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

In a study of twenty-seven patients with partial thickness burn wound, they were treated with aloe vera gel compared with vaseline gauze. It revealed the aloe vera gel treated lesion healed faster than the vaseline gauze area. The average time of healing in the aloe gel area was 11.89 days and 18.19 days for the vaseline gauze treated wound. Statistical analysis by using t-test and the value of P < 0.002 was statistically significant. In histologic study, it showed early epithelialization in the treated aloe vera gel area. Only some minor adverse effects, such as discomfort and pain were encountered in the 27 cases. This study showed the effectiveness of aloe vera gel on a partial thickness burn wound, and it might be beneficial to do further trials on burn wounds.

Here is a possible explanation  of why aloe works well with burns, since it limits the inflammation usually seen with burns. The following abstract could also be categorized as evidence for aloe’s immunomodulatory properties.

 
Effects of Aloe vera on leukocyte adhesion and TNF-alpha and IL-6 levels in burn wounded rats.

Duansak D, Somboonwong J, Patumraj S.

Inter-Department of Physiology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.

The effects of Aloe vera on microcirculation and levels of TNF-alpha and IL-6 were investigated in rats after inducing burn. Seventy-two male Wistar Furth rats were equally divided into four groups as follow: controls (CON), untreated burn-wound rats (BURN), normal saline-treated burn-wound rats (BURN-NSS) and Aloe vera-treated burn-wound rats (BURN-ALOE). The animals in each group were equally subdivided into three subgroups for the study on day 3, 7 and 14 post-burn. Dorsal skinfold chamber preparation and intravital fluorescence microscopic technique were performed to examine leukocyte adhesion on postcapillary venules. ELISA techniques were performed to examine serum TNF-alpha and IL-6 levels. It was found that the amount of leukocyte adhesion was significantly reduced in the BURN-ALOE group compared to rats in the BURN group on day 14. Levels of TNF-alpha and IL-6 were also decreased significantly compared to BURN at all three monitored time points. Aloe vera could inhibit the inflammatory process following burn injury, as characterized by the reduction of leukocyte adhesion, as well as those pro-inflammatory cytokines.
A contrasting report on aloe and burn healing in an experimental model:

Aloe vera gel hindered wound healing of experimental second-degree burns: a quantitative controlled study.

Kaufman T, Kalderon N, Ullmann Y, Berger J.

Faculty of Medicine, Technion-Israel Institute of Technology, Israel.

In the present study, Aloe vera gel (AVG) was applied to experimental second-degree burns in guinea pigs, and its effects on epithelialization, wound contraction, newly formed granulation tissue, and regeneration of hair follicles was compared with that effected by 1% silver sulfadiazine cream (AgSD). Epithelialization (%mean +/- SEM) on postburn day 8, 16, and 24 of the AVG-treated wounds was 38.72% +/- 2.71%, 60.34% +/- 3.28%, and 92.46% +/- 2.26%, respectively, while that of the AgSD-treated burns was 53.35% +/- 2.65%, 94.84% +/- 2.65%, and 100%, respectively (P less than .001). Contraction of the AVG-wounds was significantly higher than that of the AgSD-treated burns during 24 days of the study (P less than .001). The thickness of the newly formed granulation tissue was higher in the AVG-treated wounds (P less than .001), while the hair follicles count was significantly lower (P less than .001) compared with the AgSD-treated burns. It is concluded that this preparation of Aloe vera gel hindered the healing process of the present burn wound model when compared with 1% silver sulfadiazine cream.
Clearly a controversial issue in the late eighties and early nineties, but seemingly resolved in favor of aloe more recently:

Comparative evaluation of aloe vera in the management of burn wounds in guinea pigs.

Rodriguez-Bigas M, Cruz NI, Suarez A.

Surgical Research Laboratories, University of Puerto Rico School of Medicine, San Juan.

An experimental study was designed using Hartley guinea pigs, who received full-thickness burns covering 3 percent of their body surface area by direct contact with a hot plate. A total of 40 animals were equally divided among four modalities of closed burn wound management as follows: group I: silver sulfadiazine (Silvadine); group II: aloe vera gel extract (Carrington Dermal Wound Gel); group III: salicylic acid cream (aspirin); and group IV: plain gauze occlusive dressing only. The dressings were changed daily, and the size and appearance of each burn wound were recorded until complete healing. On the sixth postburn day, quantitative burn wound cultures were made. The average time to complete healing in the control group was 50 days, and the only significant difference was found in the aloe vera-treated animals, which healed on an average of 30 days (p less than 0.02). Wound bacterial counts were effectively decreased by silver sulfadiazine (p = 0.015) and by aloe vera extract (p = 0.015). From our data it appears that aloe gel extracts permit a faster healing of burn wounds.
In addition to the conclusion of faster wound healing, note also that the topical antibiotic sulfadiazine cream and aloe reduced wound bacterial counts identically. This underscores the antibiotic properties of aloe.
After dermabrasion, a deliberate form of injury induced by cosmetic surgeons to reduce or eliminate the skin changes of aging or acneiform scarring, note what these authors say about aloe:

The stimulation of postdermabrasion wound healing with stabilized aloe vera gel-polyethylene oxide dressing.

Fulton JE Jr.

Acne Research Institute, Newport Beach, CA 92663.

Full-face dermabrasion provided an ideal opportunity to document the effects of dressings on wound healing management. Following the procedure, the abraded face was divided in half. One side was treated with the standard polyethylene oxide gel wound dressings. The other side was treated with a polyethylene oxide gel dressing saturated with stabilized aloe vera. The polyethylene oxide dressing provided an excellent matrix for the release of aloe vera gel during the initial 5 days of wound healing. By 24-48 hours there was dramatic vasoconstriction and accompanying reduction in edema on the aloe-treated side. By the third to fourth day there was less exudate and crusting at the aloe site, and by the fifth to sixth day the reepithelialization at the aloe site was complete. Overall, wound healing was approximately 72 hours faster at the aloe site. This acceleration in wound healing is important to reduce bacterial contamination, subsequent keloid formation, and/or pigmentary changes. The exact mechanism of acceleration of wound healing by aloe vera is unknown
Following is a contrasting view with a few case reports of adverse reaction to application of aloe and Vitamin E following dermabrasion.
Unfortunately, we do not know how many of the four reported cases had chemical peel vs. dermabrasion.  Neither do we know whether other aspects reported above, such as the use of standard polyethelene oxide gel wound dressings were applied when aloe and vitamin E were used.

Adverse reactions to vitamin E and aloe vera preparations after dermabrasion and chemical peel.

Hunter D, Frumkin A.

College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.

Three women and one man aged forty-one to sixty-five years experienced a severe burning sensation following the application of aloe vera or vitamin E preparations to a skin area that had been subjected to a chemical peel or dermabrasion. Subsequently, a severe dermatitis occurred that required hospitalization of one patient and intravenous administration of steroids. The dermatitis abated very slowly in all patients: full recovery took three months or more. One patient resumed the use of vitamin E creams two years after the episode of dermatitis and experienced no adverse effect. Patients undergoing dermabrasion or chemical peel procedures should be cautioned specifically against the use of aloe vera or vitamin E topically in the first weeks after surgery.
This study suggests aloe would help abate ocular inflammation.

Biopharmaceutical assessment of eye drops containing aloe (Aloe arborescens Mill.) and neomycin sulphate.

Kodym A, Grzeskowiak E, Partyka D, Marcinkowski A, Kaczynska-Dyba E.

Department of Drug Form Technology, Karol Marcinkowski Medical Academy in Poznan.

The subject of the studies was eye drops made of aloe, containing the group of aloe chemical substances of anti-inflammatory use and neomycin sulphate. The aim of the studies was to evaluate the permeability of biologically active aloe substances, determined as aloenin, through synthetic lipophilic and hydrophilic membranes in a standard perfusion apparatus and in vitro verification of the transport possibilities of these substances through the isolated cornea of pig's eye. The permeability process of biologically active aloe substances determined as aloenin, through synthetic lipophilic and hydrophilic membranes, was analyzed using the first-order kinetics. Estimated quotas of permeability rate constant show that the investigated chemical compounds of aloe, included in the eye drops, diffused through the applied membranes. The studies of permeability through isolated pig's cornea proved that biologically active aloe substances could not overcome this biological barrier. On the basis of biopharmaceutical studies it can be concluded that the eye drops containing aloe and neomycin sulphate, due to the lack of permeating abilities through the eye cornea, should be particularly useful in the treatment of inflammations and infections of external parts of the eye, such as conjuctiva, eyelid edges, lacrimal sac and cornea.
And further:

Technology of eye drops containing aloe (Aloe arborescens Mill.--Liliaceae) and eye drops containing both aloe and neomycin sulphate.

Kodym A, Marcinkowski A, Kukula H.

Department of Drug Form Technology, Ludwik Rydygier Medical University in Bydgoszcz.

Eye drops made of aloe are a sterile, aqueous extract of fresh leaves of Aloe arborescens Mill., containing necessary additives and neomycin sulphate. The aim of the studies was to establish the technology of eye drops containing biologically active aloe substances and those containing both chemical constituents of aloe and neomycin sulphate. Within the studies, the formulary content and the way of preparing eye drops were determined, criteria were defined and methods of qualitative assessment of drops were proposed. On the basis of the proposed analytical methods, the physicochemical and microbiological stability of the eye drops stored at a temperature of 20-25 degrees C was studied. As the criteria of qualitative assessment of the eye drops, the following analyses were considered: sterility, appearance of the eye drops (clarity), pH, osmotic pressure, density, viscosity, TLC analysis, content of aloenin and aloin, studies of anti-microbial activity of neomycin in the drops, and preservative efficiency of thiomersal in the eye drops. The studies showed that the additives such as: sodium chloride, benzalkonium chloride, chlorhexidine diacetate and digluconate, phenylmercuric borate and Nipagins M and P could not be used to prepare the eye drops because they were involved in pharmaceutical interactions with chemical constituents of aloe in the eye drops. The eye drops containing: aqueous extract of fresh leaves of aloe, boric acid, thiomersal, sodium pyrosulphite, disodium EDTA, beta-phenylethyl alcohol and neomycin sulphate, both freshly prepared and after two years of storage, met the requirements of the Polish Pharmacopoeia (PPh V) mentioned in the monograph Guttae ophthalmicae. They were sterile, clear, their osmotic pressure approximated the osmotic pressure of lacrimal fluid and they were characterized by appropriate pH. Aloenin in the drops was much more stable than aloin. Neomycin after two years of storage retained almost 98% of its starting antimicrobial activity which allows the conclusion that the biologically active aloe substances did not decrease the stability of neomycin in the drops. The preservation assay showed that thiomersal, both in the freshly prepared drops and after two years of storage, maintained antimicrobial activity, which was in accordance with PPh V.
More on the mechanism of anti-inflammatory activity:

 
Antiinflammatory activity of extracts from Aloe vera gel.

Vazquez B, Avila G, Segura D, Escalante B.

Laboratory of Pharmacology, Escuela Nacional de Estudios Profesionales Iztacala (E.N.E.P-I), Universidad Nacional Autonoma de Mexico, Tlalnepantla, Mexico.

We studied the effects of aqueous, chloroform, and ethanol extracts of Aloe vera gel on carrageenan-induced edema in the rat paw, and neutrophil migration into the peritoneal cavity stimulated by carrageenan. We also studied the capacity of the aqueous extract to inhibit cyclooxygenase activity. The aqueous and chloroform extracts decreased the edema induced in the hind-paw and the number of neutrophils migrating into the peritoneal cavity, whereas the ethanol extract only decreased the number of neutrophils. The antiinflammatory agents indomethacin and dexamethasone also decreased carrageenan-induced edema and neutrophil migration. The aqueous extract inhibited prostaglandin E2 production from [14C]arachidonic acid. The chemical tests performed in the aqueous extract for anthraglycosides, reductor sugars and cardiotonic glycosides were positive. In the ethanol extract, the chemical tests performed for saponins, carbohydrates naftoquinones, sterols, triterpenoids and anthraquinones were also positive. In the chloroform extract, the chemical tests performed for sterols type delta 5, and anthraquinones were positive. These results demonstrated that the extracts of Aloe vera gel have antiinflammatory activity and suggested its inhibitory action on the arachidonic acid pathway via cyclooxygenase.

New chemically active compounds continue to be discovered in aloe plants from different regions.

 
Antiinflammatory C-glucosyl chromone from Aloe barbadensis.

Hutter JA, Salman M, Stavinoha WB, Satsangi N, Williams RF, Streeper RT, Weintraub ST.

Department of Pharmacology, Research Imaging Center, University of Texas Health Science Center at San Antonio, 78284-7760, USA.

A new antiinflammatory agent identified as 8-[C-beta-D-[2-O-(E)-cinnamoyl]glucopyranosyl]-2- [(R)-2-hydroxypropyl]-7-methoxy-5-methylchromone (1) has been isolated from Aloe barbadensis Miller. At a dose of 200 microg/mouse ear, 1 exhibited topical antiinflammatory activity equivalent to 200 microg/ear of hydrocortisone. There was no reduction in thymus weight caused by treatment with 1 for any of the doses tested, while 200 microg/ear of hydrocortisone resulted in a 50% decrease in thymus weight.
Antioxidant properties

The following study elucidates possible mechanisms for aloe as an antioxidant.

 
Antioxidant, free radical scavenging and anti-inflammatory effects of aloesin derivatives in Aloe vera.

Yagi A, Kabash A, Okamura N, Haraguchi H, Moustafa SM, Khalifa TI.

Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuen-cho, Fukuyama, Japan. yagi@fupharm.fukuyama-u.ac.jp

Antioxidant components in Aloe vera were examined for lipid peroxidation using rat liver microsomal and mitochondrial enzymes. Among the aloesin derivatives examined, isorabaichromone showed a potent antioxidative activity. The DPPH radical and superoxide anion scavenging activities were determined. As one of the most potent components, isorabaichromone together with feruloylaloesin and p-coumaroylaloesin showed potent DPPH radical and superoxide anion scavenging activities. Electron spin resonance (ESR) using the spin trapping method suggested that the potent superoxide anion scavenging activity of isorabaichromone may have been due to its caffeoyl group. As A. vera has long been used to promote wound healing, the inhibitory effects of aloesin derivatives for cyclooxygenase (Cox)-2 and thromboxane (Tx) A 2 synthase were examined and the participation of p-coumaroyl and feruloyl ester groups in the aloesin skeleton was demonstrated. These findings may explain, at least in part, the wound healing effects of A. vera. Abbreviations. ADP: adenosine diphosphate ASA: ascorbic acid BHT: butylated hydroxytoluene BSA: bovine serum albumin DMPO:5,5-dimethyl-1-pyrroline N-oxide DPPH:1,1-diphenyl-2-picrylhydrazyl EDTA: eidetic acid HEPES: N-(2-hydroxyethyl)-piperazine- N-2'-ethane-sulfonic acid NADH: reduced nicotinamide adenine dinucleotide NADPH: reduced nicotinamide adenine dinucleotide phosphate NBT: nitroblue tetrazolium Pg: prostaglandin SOD: Superoxide dismutase TBA: thiobarbituric acid TCA: trichloroacetic acid XOD: xanthine oxidase
More on antioxidant properties and potency of aloe related to the age of the plant at harvest:

 
Evaluation of antioxidant potential of aloe vera (Aloe barbadensis miller) extracts.

Hu Y, Xu J, Hu Q.

College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, PRC.

The polysaccharide and flavonoid concentrations of two-, three-, and four-year-old Aloe vera were determined, and their antioxidant activities were evaluated compared to BHT and alpha-tocopherol by the DPPH radical scavenging method and the linoleic acid system at 100 microg of soluble solids per mL of ethanol. The results showed that three-year-old Aloe vera contained significantly higher levels of polysaccharides and flavonoids than two- and four-year-old Aloe vera, and no significant differences in flavonoid levels were found between three- and four-year-old Aloe vera. All the aloe extracts showed significant antioxidant activity. The antioxidant activity of Aloe vera extracts and reference compounds followed the order: three-year-old Aloe vera > BHT > four-year-old Aloe vera > alpha-tocopherol > two-year-old Aloe vera. The three-year-old extract exhibited the strongest radical scavenging activity of 72.19%, which is significantly higher than that of BHT at 70.52% and alpha-tocopherol at 65.20%. These data suggest that the growth stage plays a vital role in the composition and antioxidant activity of Aloe vera.
Angiogenic properties
Another positive factor regarding aloe’s promoting wound healing relates to this study demonstrating that aloe gel promotes new blood vessel formation.

 
A novel angiogenic factor derived from Aloe vera gel: beta-sitosterol, a plant sterol.

Moon EJ, Lee YM, Lee OH, Lee MJ, Lee SK, Chung MH, Park YI, Sung CK, Choi JS, Kim KW.

Department of Molecular Biology, Pusan National University, Pusan, Korea.

Aloe vera gel has a beneficial effect on wound healing. Because angiogenesis is an essential process in wound healing, we hypothesized that Aloe vera gel might contain potent angiogenic compounds. Here we demonstrate that Aloe vera gel and its extracts are angiogenic on the chorioallantoic membrane (CAM) of chick embryo. Out of the three compounds purified from the final fraction of Aloe vera gel, beta-sitosterol showed a potent angiogenic activity in the CAM assay. In the presence of heparin, beta-sitosterol stimulated neovascularization in the mouse Matrigel plug assay and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay. Thus beta-sitosterol is a novel plant-derived angiogenic factor which may have potential pharmaceutical applications for the management of chronic wounds.
Immune system modulator
The history of immunopharmacologygives insight into the mechanism of anti-inflammatory activity and immune modulation of Aloe vera gel.
Note: Serum complement represents a series of numbered molecules that are signaling devices used in immunologically active inflammatory processes leading to antibody responses against specific antigens.  The study below focuses on C-3.

An anti-complementary polysaccharide with immunological adjuvant activity from the leaf parenchyma gel of Aloe vera.

t'Hart LA, van den Berg AJ, Kuis L, van Dijk H, Labadie RP.

The aim of the study is to develop new substances with immunomodulatory activity. To this end, extracts from plants used in traditional medicine are used as starting material. This study deals with the mucilagenous leaf-gel of Aloe vera which is well reputed for its therapeutical effect on inflammatory-based disorders. The purification of an aqueous gel-extract guided by inhibition of complement activity in HPS is described. Using anion-exchange and gel permeation chromatography a highly active polysaccharide fraction was isolated, that is present in the gel in various chain lengths. The polysaccharides consist of several monosaccharides of which mannose is dominant. The inhibition is based on alternative pathway activation, resulting in consumption of C3. With respect to their biological activity the polysaccharides inhibit the opsonization of zymosan in HPS and display adjuvant activity on specific antibody production and the induction of delayed type hypersensitivity in mice.
The immunological effects of acemannan, one of many active compounds in aloe, may explain aloe’s antiviral capabilities observed more recently and focused on later in the Library.

Enhancement of allo-responsiveness of human lymphocytes by acemannan (Carrisyn).

Womble D, Helderman JH.

Renal Immunology Laboratory, University of Texas Southwestern Medical Center, Dallas.

Healing powers have been imputed as being a feature of the gel from the aloe vera plant for centuries. The recent isolation of the active ingredient, acemannan, has made testing of this drug important. Since the drug appears to enhance monocyte function in other experiments, these studies were designed to test the capacity of acemannan to enhance immune response to alloantigen (foreign) and to test whether the potential enhancement is a monocyte driven phenomenon. Acemannan did not enhance lymphocyte response to syngeneic (self) antigens in the mixed lymphocyte culture (MLC) but importantly increased alloantigenic response in a dose-response fashion (2.6 x 10(-7) - 2.6 x 10(-9)M). This effect of acemannan was shown to be a specific response and to concur with concentrations of in vitro acemannan achievable in vivo. A separate series of mixing experiments demonstrated that acemannan incubation with monocytes permitted monocyte driven signals to enhance T-cell response to lectin. It is concluded that acemannan, the active ingredient of the aloe vera plant, is an important immunoenhancer in that it increases lymphocyte response to alloantigen. It is suggested that the mechanism involves enhancement of monocyte release of IL-I under the aegis of alloantigen. This mechanism may explain in part the recently observed capacity of acemannan to abrogate viral infections in animal and man.

The next abstract describes a recent discovery of a new immunologically active compound within aloe juice contributing to its immunomodulatory properties.

 
Characterization of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity.

Pugh N, Ross SA, ElSohly MA, Pasco DS.

Department of Pharmacognosy, National Center for Natural Products Research, University of Mississippi, University, Mississippi 38677, USA.

We have characterized a new immunostimulatory polysaccharide called Aloeride from commercial aloe vera (Aloe barbadensis) juice. Aloeride is between 4 and 7 million Da [Editor’s note: Da is an abbreviation for Dalton, which is a unit of molecular weight], and its glycosyl components include glucose (37.2%), galactose (23.9%), mannose (19.5%), and arabinose (10.3%). At 0.5 microg/mL Aloeride increased NF-kappa B directed luciferase expression in THP-1 human monocytic cells to levels 50% of those achieved by maximal concentrations (10 microg/mL) of LPS (lipopolysacharrides). Aloeride induced the expression of the mRNAs encoding IL-1beta and TNF-alpha to levels equal to those observed in cells maximally activated by LPS. Acemannan, the major carbohydrate component from aloe, used at 200 microg/mL in the macrophage assay resulted in negligible NF-kappa B activation. Analysis of acemannan and Aloeride using size-exclusion chromatography suggests that the low activity of acemannan is due to trace amounts of Aloeride. Although Aloeride comprises only 0.015% of the aloe juice dry weight, its potency for macrophage activation accounts fully for the activity of the crude juice.
Tumor suppressive / cancer preventive

A comparative study of the anticancer and cancer chemo-preventive properties of several medicinal plants, leading with Aloe vera, follows.  The term “DNA adduct formation” means that the structure/function of a segment of DNA on which specific genes are located has been damaged by oxidation.  The damaged segment is called an adduct. When the genes are damaged, cancer can be a likely outcome.

 
In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis miller, Lentinus edodes, Ganoderma lucidum and Coriolus versicolor).

Kim HS, Kacew S, Lee BM.

Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Changan-ku, Chunchun-dong, Kyunggi-do, Suwon 440-746, Korea.

A plant polysaccharide, Aloe gel extract, was reported to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA adduct formation in vitro and in vivo. Hence, chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] were compared using in vitro short-term screening methods associated with both initiation and promotion processes in carcinogenesis. In B[a]P-DNA adduct formation, APS (ALOE PLANT POLYSACCHARIDES) (180 micrograms/ml) was the most effective in inhibition of B[a]P binding to DNA in mouse liver cells. Oxidative DNA damage (by 8-hydroxydeoxyguanosine) was significantly decreased by APS (180 micrograms/ml) and CPS (180 micrograms/ml). In induction of glutathione S-transferase activity, GPS was found to be the most effective among plant polysaccharides. In screening anti-tumor promoting effects, APS (180 micrograms/ml) significantly inhibited phorbol myristic acetate (PMA)-induced ornithine decarboxylase activity in Balb/3T3 cells. In addition, APS significantly inhibited PMA-induced tyrosine kinase activity in human leukemic cells. APS and CPS significantly inhibited superoxide anion formation. These results suggest that some plant polysaccharides produced both anti-genotoxic and anti-tumor promoting activities in in vitro models and, therefore, might be considered as potential agents for cancer chemoprevention.
The next abstract states:“These results suggest that Aloe vera gel contains at least two small molecular weight immunomodulators that may prevent UVB-induced immune suppression in the skin.”

Based upon the following, it is conceivable that the inhibition by aloe of the production of melanin and proliferation of melanocytes noted in the next study may suggest a preventive influence over the development of melanoma, a skin malignancy directly related to overexposure to UV sun irradiation.

Prevention of ultraviolet radiation-induced suppression of accessory cell function of Langerhans cells by Aloe vera gel components.

Lee CK, Han SS, Mo YK, Kim RS, Chung MH, Park YI, Lee SK, Kim YS.

College of Pharmacy, Chungbuk National University, Cheongju, South Korea.

The active components of Aloe vera gel that can prevent ultraviolet B (UVB)-induced suppression of accessory cell function of Langerhans cells (LC) were purified by activity-guided sequential fractionation [Editor’s note:  These cells referred to as LC are intrinsic to the epidermis and are affected by UV radiation, as in sunburn.  It is important to note the relationship between overexposure of skin to sunlight and the incidence and prevalence of a variety of skin cancers.] followed by in vitro functional assay. The functional assay was based on the fact that exposure of freshly isolated murine (MOUSE) epidermal cells (EC) to UVB radiation resulted in impairment of accessory cell function of LC, as measured by their ability to support anti-CD3 monoclonal antibody (mAb)-primed T-cell mitogenesis. [Editor’s note: The above is a description of the model the researchers created of a specific cell type induced to malfunction immunologically.] This UVB-suppressed LC accessory cell function was prevented by addition of partially purified aloe gel components to cultures of UVB-irradiated EC. The aloe gel components appeared to prevent events occurring within the first 24 h after UVB irradiation that lead to the impairment of accessory cell function. The aloe gel components did not cause proliferation of anti-CD3 mAb-primed T-cells, nor did [they] induce proliferation of normal EC. The activity-guided final purification of aloe gel components resulted in the isolation of two components. Both of the components were small molecular weight (MW) substances with an apparent MW of less than 1,000 Da but different from each other in net charge characteristics at pH 7.4. These results suggest that Aloe vera gel contains at least two small molecular weight immunomodulators that may prevent UVB-induced immune suppression in the skin.
One other cancer-preventive mechanism for aloesin, another potential application for aloe, emerges which appears to support a mechanism for preventing UV stimulation of melanocyte transformation to melanoma.

 
Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase.

Jones K, Hughes J, Hong M, Jia Q, Orndorff S.

Univera Pharmaceuticals Inc., Broomfield, CO 80021, USA. ken@aloecorp.com

Aloesin, [2-acetonyl-8-beta-d-glucopyranosyl-7-hydroxy-5-methylchromone], a compound isolated from the Aloe plant, is shown in these studies to modulate melanogenesis via competitive inhibition of tyrosinase. Aloesin inhibits purified tyrosinase enzyme and specifically inhibits melanin production in vitro. Enzyme kinetics studies using normal human melanocyte cell lysates and cell-based melanin production demonstrated that aloesin is a competitive inhibitor of tyrosinase from mushroom, human and murine sources. Tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human melanocyte cell lysates were inhibited by aloesin in a dose dependent manner. In a percutaneous absorption study a finite dose of aloesin penetrated the skin slowly and was recovered primarily in the surface wash. Aloesin shows promise as a pigmentation-altering agent for cosmetic or therapeutic applications.

Tumor Suppressive:

Antitumor effects from Aloe vera have been studied and noted:

 
Anti-leukaemic and anti-mutagenic effects of di(2-ethylhexyl)phthalate isolated from Aloe vera Linne.

Lee KH, Kim JH, Lim DS, Kim CH.

Animal Resource Research Center, Konkuk University, Seoul, Korea.

Extracts of Aloe vera Linne have been found to exhibit cytotoxicity against human tumour cell lines. This study examines the anti-tumour effects of di(2-ethylhexyl)phthalate (DEHP) isolated from Aloe vera Linne, in human and animal cell lines. Its anti-mutagenic effects were examined using Salmonella typhimurium TA98 and TA100 strains. Growth inhibition was specifically exerted by DEHP against three leukaemic cell lines at concentrations below 100 microg mL(-1). At 100 microg mL(-1) DEHP, K562, HL60 and U937 leukaemic cell lines showed growth inhibition of 95, 97 and 95%, respectively. DEHP exhibited an inhibitory activity of 74, 83 and 81%, respectively, in K562, HL60 and U937 cell lines at a concentration of 10 microg mL(-1). At a concentration of 1 microg mL(-1), DEHP exerted an inhibitory activity of 50, 51 and 52%, respectively, in K562, HL60 and U937. In a normal cell line, MDBK, DEHP exerted 30% growth inhibition at a concentration of 100 microg mL(-1), and showed no inhibitory activity at concentrations below 50 microg mL(-1). It was found that DEHP exerted anti-mutagenic activity in the Salmonella mutation assay. The number of mutant colonies of Salmonella typhimurium strain TA98 upon exposure to AF-2 (0.2 microg/plate) decreased in a concentration-dependent manner in the presence of different DEHP concentrations (decreasing to 90.4, 83.9, 75.4, 69.6 and 46.9%, respectively, for DEHP concentrations of 100, 50, 10, 5 and 1 microg/plate). In the case of Salmonella typhimurium strain TA100, DEHP reduced AF-2-induced mutagenicity at 1, 5, 10, 50 and 100 microg/plate to 57.4, 77.5, 80.0, 89.0 and 91.5%, respectively. The isolated compound from Aloe vera Linne, DEHP, was considered to be the active principle responsible for anti-leukemic and anti-mutagenic effects in-vitro.
Some of the same research group amplify:

 
Induction of apoptosis in human leukaemic cell lines K562, HL60 and U937 by diethylhexylphthalate isolated from Aloe vera Linne.

Lee KH, Hong HS, Lee CH, Kim CH.

Animal Resource Research Center, Konkuk University, Seoul, Korea.

We investigated the effect of diethylhexylphthalate (DEHP) from Aloe vera Linne on the apoptosis of human leukaemic cell lines K562, HL60 and U937 to examine its pharmacological activity. At a level of 10 microg mL(-1) DEHP a significant anti-leukemic effect was observed for all three cell lines, as measured by clonogenic assay. After treatment with 10 microg mL(-1) DEHP for 4 h, agarose gel electrophoresis and flow cytometric analysis confirmed the occurrence of apoptosis. These results indicate that DEHP isolated from Aloe vera Linne has a potent antileukemic effect, and thus represents a new type of pharmacological activity with respect to human leukemic cells.

A variety of possible anticancer mechanisms attributable to aloe:

 
Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells.

Chen HC, Hsieh WT, Chang WC, Chung JG.

Department of Pharmcology, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan, ROC.

In this study, we have evaluated the chemopreventive role of aloe-emodin in human promyelocytic leukemia HL-60 cells in vitro by studying the regulation of proliferation, cell cycle and apoptosis [Editor’s note: apoptosis = programmed cell death]. Aloe-emodin inhibited cell proliferation and induced G2/M arrest and apoptosis in HL-60 cells. Investigation of the levels of cyclins B1, E and A by immunoblot analysis showed that cyclin E level was unaffected, whereas cyclin B1 and A levels increased with aloe-emodin in HL-60 cells. Investigation of the levels of cyclin-dependent kinases, Cdk1 and 2, showed increased levels of Cdk1 but the levels of Cdk2 were not effected with aloe-emodin in HL-60 cells. The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 microM aloe-emodin for 12, 24, 48, and 72 hours. Taken together, aloe-emodin therefore appears to exert its anticarcinogenesis properties by inhibiting proliferation and inducing cell cycle arrest and apoptosis underwent activation of caspase-3 in human leukemia HL-60 cells.
Aloe emodin is an effective anticancer agent in another specific type of cancer:

 
Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors.

Pecere T, Gazzola MV, Mucignat C, Parolin C, Vecchia FD, Cavaggioni A, Basso G, Diaspro A, Salvato B, Carli M, Palu G.

Department of Histology, Microbiology, and Medical Biotechnologies, Medical School, University of Padova, Italy.

Here we report that aloe-emodin (AE), a hydroxyanthraquinone present in Aloe vera leaves, has a specific in vitro and in vivo  antineuroectodermal tumor activity. [Editor’s note: in vivo means in living organisms while in vitro means in some type of extracorporeal experimental situation, as “in a test tube.”] The growth of human neuroectodermal tumors is inhibited in mice with severe combined immunodeficiency without any appreciable toxic effects on the animals. The compound does not inhibit the proliferation of normal fibroblasts nor that of hemopoietic progenitor cells. The cytotoxicity mechanism consists of the induction of apoptosis, whereas the selectivity against neuroectodermal tumor cells is founded on a specific energy-dependent pathway of drug incorporation. Taking into account its unique cytotoxicity profile and mode of action, AE might represent a conceptually new lead antitumor drug.

Another recent and similar study on Merkel cell carcinoma cells shows aloe-emodin’s efficacy in fighting cancer:

 
The effect of aloe emodin on the proliferation of a new merkel carcinoma cell line.

Wasserman L, Avigad S, Beery E, Nordenberg J, Fenig E.

Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Rabin Medical Center Beilinson Campus, Petah Tikva 49100, Israel. yardenam@clalit.org.ie

A free-floating cell line has been established from a metastatic lesion of a Merkel cell carcinoma (MCC) patient. [Editor’s note: This means that these cells were grown from an actual patient’s cancer in cell culture conditions, so that in theory what happens to these cells in culture should happen to the tumor cells in the patient.] The cell line was characterized by immunocytochemical reactions with antibodies against the epithelial and neuroendocrine antigens: cytokeratin 20, neuron-specific enolase, chromogranin A, neurofilament protein, synaptophysin, and calcitonin. Karyotype analysis of the MCC cells showed deletion in chromosomes 3 and 7, loss of chromosome 10, and several translocations in other chromosomes. No mutation was detected in the TP53 gene, after analyzing the complete coding region. Growth factors such as basic fibroblast growth factor, transforming growth factor-beta, and nerve and epidermal growth factors had no effect on the proliferation of the cells. The differentiation-inducing agents sodium butyrate and dimethyl sulfoxide, especially the former, markedly inhibited the proliferation of the MCC cells. Aloe emodin, a natural constituent of aloe vera leaves, significantly inhibited the growth of MCC cells. Aloe emodin has been reported to be nontoxic for normal cells but to possess specific toxicity for neuroectodermal tumor cells. Differentiation-inducing agents, and aloe emodin, merit further investigation as potential agents for treating MCC.
Merkel cell carcinoma (MCC), discussed above, which is resistant to most forms of chemotherapeutic intervention, may benefit from aloe-emodin plus low concentrations of other potent anticancer drugs.

Combined effect of aloe-emodin and chemotherapeutic agents on the proliferation of an adherent variant cell line of Merkel cell carcinoma.

Fenig E, Nordenberg J, Beery E, Sulkes J, Wasserman L.

Institute of Oncology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel. efenig@clalit.org.il

Merkel cell carcinoma (MCC) has only limited sensitivity to chemotherapeutic agents. The aim of the study was to determine if members of the anthraquinone family could be used as adjuncts to increase the growth inhibiting effect of anticancer agents in MCC. An adherent variant of MCC was derived from a previously established MCC cell line suspension. Cells were characterized by immunocytochemical methods using specific antibodies against epithelial (low molecular weight cytokeratins and cytokeratin 20) and neuroendocrine (neuron-specific enolase, neurofilament protein, chromogranin A and synaptophysin) antigens. Emodin and aloe-emodin, members of the anthraquinone family, inhibited proliferation of the adherent MCC cells, with a slight advantage of aloe-emodin over emodin. Aloin had no effect on cell proliferation. The chemotherapeutic agents, cis-platinol (abiplastin), doxorubicin (adriablastin), and 5-fluorouracil, and the tyrosine kinase inhibitor STI 571, all independently inhibited the proliferation of adherent MCC cells. The addition of aloe-emodin potentiated their inhibitory effect, especially when low concentrations of the anticancer compounds were used. [Editor’s note: The value of this finding suggests that by adding in the benefit of the anthraquinones of aloe emodin, one can use lower concentrations of toxic anticancer  drugs and get even better results against the cancer than obtainable with the toxic drugs by themselves.] The antiproliferative action of STI 571 may be associated with the presence of anti-c-kit antibodies. The combined use of anticancer agents, especially at low concentrations, and aloe-emodin may be considered a preferable means for treating MCC.
Two genetic mechanisms operate through aloe-emodin-induced arrest of cancer cell proliferation in two different liver cancer cell lines and are potentially protective of liver cells becoming cancerous.

 
The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines.

Kuo PL, Lin TC, Lin CC.

Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.

The aim of this study is to investigate the anticancer effect of aloe-emodin in two human liver cancer cell lines, Hep G2 and Hep 3B. We observed that aloe-emodin inhibited cell proliferation and induced apoptosis in both examined cell lines, but with different antiproliferative mechanisms. In Hep G2 cells, aloe-emodin induced p53 expression and was accompanied by induction of p21 expression that was associated with a cell cycle arrest in G1 phase. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. In contrast, with p53-deficient Hep 3B cells, the inhibition of cell proliferation of aloe-emodin was mediated through a p21-dependent manner that did not cause cell cycle arrest or increase the level of Fas/APO1 receptor, but rather promoted aloe-emodin induced apoptosis by enhancing expression of Bax. These findings suggest that aloe-emodin may be useful in liver cancer prevention.
More on antitumor potential of aloe:

 
Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells.

Lee JK, Lee MK, Yun YP, Kim Y, Kim JS, Kim YS, Kim K, Han SS, Lee CK.

College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.

Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.
And:

The therapeutic potential of Aloe Vera in tumor-bearing rats.

Corsi MM, Bertelli AA, Gaja G, Fulgenzi A, Ferrero ME.

Institute of General Pathology, Medical Faculty, University of Milan, Italy.

Aloe Vera has been claimed to contain several important therapeutic properties, including anticancer effects. The effect of Aloe Vera administration was studied on a pleural tumor in rat. Growth of Yoshida AH-130 ascite hepatoma cells injected (2 x 10(5) in 0.1 ml) into pleura of male inbred Fisher rats was evaluated at different times (7th and 14th days). Data show that the use of Aloe Vera proved a therapeutic method, and that the present experimental model could be useful in the study of other therapeutics treatments in vivo.
And:

[Antimetastatic properties of aloe juice]

[Abstract in Russian]

Gribel' NV, Pashinskii VG.

An evaluation of antimetastatic properties of succus Aloes was carried out using three types of experimental tumors of mice and rats. It was found that succus Aloes treatment contributes to reduction of tumor mass, metastatic foci and metastasis frequency at different stages of tumor progress without affecting major tumor growth. Succus Aloes potentiates the antitumor effect of 5-fluorouracil and cyclophosphamide as components of combination chemotherapy.
The following contrasting abstract found accentuating genotoxicity of an aloe derivative, therefore, proposing a contrary view that aloe might instead be a risk for cancer induction:

Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II mediated?

Muller SO, Eckert I, Lutz WK, Stopper H.

Department of Toxicology, University of Wurzburg, Germany.

1,8-Dihydroxyanthraquinones are under debate as plant-derived carcinogens that are found in laxatives, food colors, and possibly vegetables. Published genotoxicity data are controversial, and so three of them (emodin, danthron and aloe-emodin) were tested in a number of in vitro assay systems. All three compounds induced tk-mutations in mouse lymphoma L5178Y cells. Induction of micronuclei also occurred in the same cell line, and was dose-dependent, with the potency ranking being danthron > aloe-emodin > emodin. In a DNA decatenation assay with a network of mitochondrial DNA of C. fasciulata, all three test compounds inhibited the topoisomerase II-mediated decatenation. Danthron and aloe-emodin, but not emodin, increased the fraction of DNA moving into comet tails when tested at concentrations around 50 microM in single-cell gel-electrophoresis assays (SCGE; comet assay). Comet assays were also used in modified form to determine whether pretreatment of the cells with the test compounds would reduce the effects of etoposide, a potent topoisomerase II inhibitor. All three test chemicals were effective in this pretreatment protocol, with danthron again being the most potent(Editor’s note: Not present in Aloe). Given clear cut evidence of their genotoxic activity, further research on the human cancer risk of these compounds may be warranted.
A cautionary abstract elucidates opposing mechanisms relevant to the anticancer properties of aloe emodin:

Aloe-emodin prevents cytokine-induced tumor cell death: the inhibition of auto-toxic nitric oxide release as a potential mechanism.

Mijatovic S, Maksimovic-Ivanic D, Radovic J, Popadic D, Momcilovic M, Harhaji L, Miljkovic D, Trajkovic V.

Department of Neurobiology and Immunology, Institute for Biological Research, 29. Novembra 142, 11000, Belgrade, Serbia and Montenegro. mamas@yubc.net

Aloe-emodin (AE) is a plant-derived hydroxyanthraquinone with potential anticancer activity. We investigated the ability of AE to modulate survival of mouse L929 fibrosarcoma and rat C6 astrocytoma cells through interference with the activation of inducible nitric oxide (NO) synthase (NOS) and subsequent production of tumoricidal free radical NO. Somewhat surprisingly, AE in a dose-dependent manner rescued interferon-gamma + interleukin-1-stimulated L929 cells from NO-dependent killing by reducing their autotoxic NO release. The observed protective effect was less pronounced in C6 cells, due to their higher sensitivity to a direct toxic action of the drug. AE-mediated inhibition of tumor cell NO release coincided with a reduction in cytokine-induced accumulation of transcription and translation products of genes encoding inducible NOS and its transcription factor IRF-1, while activation of NF-kappaB remained unaltered. These data indicate that the influence of AE on tumor growth might be more complex that previously recognized, the net effect being determined by the balance between the two opposing actions of the drug: its capacity to directly kill tumor cells, but also to protect them from NO-mediated toxicity.

The next recent study shows the immune modulatory efficacy and antitumor effects of aloe.

 
Identification of optimal molecular size of modified Aloe polysaccharides with maximum immunomodulatory activity.

Im SA, Oh ST, Song S, Kim MR, Kim DS, Woo SS, Jo TH, Park YI, Lee CK.

College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.

Polysaccharides isolated from the gel of Aloe species have been known to have diverse biological activities, including immunomodulatory and antitumor activities. The molecular size-immunomodulatory activity relationship of modified Aloe polysaccharide (MAP) was examined in this study. Crude MAP (G2E1) was prepared from the gel of Aloe vera that was partially digested with cellulase. Proteins in crude MAP were removed by passage through a DEAE-Sephacel column, and then the protein-free MAP (G2E1D) was further separated into three fractions, G2E1DS3 molecular weight (MW>/=400 KDa), G2E1DS2 (5 KDa</=MW</=400 KDa), G2E1DS1 (MW</=5 KDa), by Sephacryl column chromatography and ultrafiltration. Immunomodulatory activities of MAP preparations were examined on a mouse macrophage cell line, RAW 264.7 cells, and in ICR strain of mouse implanted with sarcoma 180 cells. We found that polysaccharides between 400 and 5 KDa exhibit the most potent macrophage-activating activity as determined by increased cytokine production, nitric oxide release, expression of surface molecules, and phagocytic activity. In accordance with the in vitro activity, polysaccharides between 400 and 5 KDa also exhibited the most potent antitumor activity in vivo.
Anti-atherogenic properties (atherosclerosis preventive: lowers cholesterol and tryglycerides; raises HDL; may actually reverse coronary artery disease; may diminish dependency on a variety of drugs)
The antioxidant ingredients of aloe have been shown to prevent lipid peroxidation and further to prevent inflammatory changes in micro injuries to the innermost lining of coronary and other blood vessels.  When one combines these properties now recognized as those  possessed by aloe with the findings in the next study, one can consider the impact of an aloe-based dietary change on 5,000 patients studied prospectively particularly fascinating with respect to the role of aloe in preventing and perhaps even reversing atherosclerosis and coronary artery disease.

Prevention of atheromatous heart disease.

Agarwal OP.

Five thousand patients of atheromatous heart disease, presented as angina pectoris, were studied over a period of five years. After adding the 'Husk of Isabgol' and 'aloe vera' (an indigenous plant known as ghee-guar-ka-paththa) to the diet, a marked reduction in total serum cholesterol, serum triglycerides, fasting and post prandial blood sugar level in diabetic patients, total lipids and also increase in HDL were noted. Simultaneously the clinical profile of these patients showed reduction in the frequency of anginal attacks and gradually, the drugs, like verapamil, nifedipine, beta-blockers and nitrates, were tapered. The patients, most benefited, were diabetics (without adding any antidiabetic drug). The exact mechanism of the action of the above two substances is not known, but it appears, that probably they act by their high fibre contents. Both these substances need further evaluation. The most interesting aspect of the study was that no untoward side effect was noted and all the five thousand patients are surviving till date.
Anti-platelet adhesive properties
A warning about herb-drug interaction, which could be life-threatening in the case of someone about to undergo surgery with sevoflurane anesthesia. This abstract, however, points out that aloe is an anti-platelet adhesive agent like low-dose aspirin and Plavix.

 
Possible interaction between sevoflurane and Aloe vera.

Lee A, Chui PT, Aun CS, Gin T, Lau AS.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.

OBJECTIVE: To describe a patient with massive intraoperative bleeding after oral consumption of Aloe vera tablets. CASE SUMMARY: A 35-year-old woman lost 5 L of blood during surgery as a result of a possible herb-drug interaction between Aloe vera and sevoflurane. DISCUSSION: Aloe vera is a common herb used for antiinflammatory and antiarthritic activity, as well as antibacterial, hypoglycemic, and lipid-lowering effects. Compounds contained within Aloe vera can cause a reduction in prostaglandin synthesis, which may inhibit secondary aggregation of platelets. Sevoflurane inhibits thromboxane A(2) formation by suppression of cyclooxygenase activity, impairs platelet aggregation, and prolongs bleeding. Although the vascularity and size of the hemangioma were the most important factors for the massive intraoperative blood loss, concomitant use of sevoflurane and Aloe vera played a contributory role. An objective causality assessment revealed that this adverse event was possible as a result of the sevoflurane and Aloe vera interaction. CONCLUSIONS: There is a potential herb-drug interaction between Aloe vera and sevoflurane based on the antiplatelet effects of these 2 agents. Herbal medications with antiplatelet potential should be discontinued before anesthesia and surgery.
Based upon the above, aloe could be an herbal means to achieve the same results as low-dose aspirin or Plavix therapy used to protect against acute coronary syndrome by reducing platelet stickiness. It should be noted that prior to anesthesia and surgery of any type, the patient is ordered to stop aspirin and drug therapy that reduces platelet adhesiveness at least two weeks prior to the operation. The reader can see yet another benefit of aloe in the context of this caution.

Anti-diabetic properties
The next abstract from 1986 illustrates two points: 1) the global recognition of the value of this genus of plant for medicinal uses and 2) the recognition of aloe as a treatment for type 2 diabetes as a blood-glucose-lowering agent.
 

The antidiabetic activity of aloes: preliminary clinical and experimental observations.

Ghannam N, Kingston M, Al-Meshaal IA, Tariq M, Parman NS, Woodhouse N.

The dried sap of the aloe plant (aloes) is one of several traditional remedies used for diabetes in the Arabian peninsula. Its ability to lower the blood glucose was studied in 5 patients with non-insulin-dependent diabetes and in Swiss albino mice made diabetic using alloxan. During the ingestion of aloes, half a teaspoonful daily for 4-14 weeks, the fasting serum glucose level fell in every patient from a mean of 273 +/- 25 (SE) to 151 +/- 23 mg/dl (p less than 0.05) with no change in body weight. In normal mice, both glibenclamide (10 mg/kg twice daily) and aloes (500 mg/kg twice daily) induced hypoglycaemia after 5 days, 71 +/- 6.2 and 91 +/- 7.6 mg/dl, respectively, versus 130 +/- 7 mg/dl in control animals (p less than 0.01); only glibenclamide was effective after 3 days. In the diabetic mice, fasting plasma glucose was significantly reduced by glibenclamide and aloes after 3 days. Thereafter only aloes was effective and by day 7 the plasma glucose was 394 +/- 22.0 versus 646 +/- 35.9 mg/dl, in the controls and 726 +/- 30.9 mg/dl in the glibenclamide treated group (p less than 0.01). We conclude that aloes contains a hypoglycemic agent which lowers the blood glucose by as yet unknown mechanisms.
More on aloe and diabetes:  Glibenclamide is a drug approved for human use that lowers blood glucose in type 2 diabetes.  In the next study, aloe worked as well as the drug did in an experimental model to diminish liver damage in type 2 diabetes.

 
Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models.
 
Can A, Akev N, Ozsoy N, Bolkent S, Arda BP, Yanardag R, Okyar A.

Department of Biochemistry, Faculty of Pharmacy, Istanbul University, Turkey.

The aim of this work was to investigate the effects of Aloe vera leaf pulp and gel extracts on the liver tissue of neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. The diabetic rats were separated into four groups and each group was given the following samples by gavage, daily for 15 d: phosphate buffered saline (PBS; diabetic control), Aloe leaf pulp extract, Aloe leaf gel extract, glibenclamide. Liver tissues were examined histologically. The markers of oxidative stress: glutathione (GSH), non-enzymatic glycosylation (NEG) and lipid peroxidation (LPO), were determined in liver tissue. Biochemical parameters for liver function: serum alkaline phosphatase (ALP), and alanine transaminase (ALP) activities, were evaluated. All parameters were also determined in healthy (non diabetic) rats for comparison. In the diabetic control group, the degenerative changes in liver tissue were remarkable, while in the diabetic groups given Aloe pulp and gel extracts and glibenclamide, the damage to the liver tissue was decreased. The increase of GSH and the decrease of NEG and LPO in liver tissues with the treatment of Aloe gel extract, are consistent with the beneficial effect of Aloe. Serum ALP and ALT activities were also decreased in the groups given Aloe gel extract. It was concluded that Aloe gel extract has a protective effect comparable to glibenclamide against hepatotoxicity produced by diabetes if used in the treatment of type-II diabetes.
More on diabetes and aloe:

 
Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models.

Okyar A, Can A, Akev N, Baktir G, Sutlupinar N.

Department of Pharmacology, Faculty of Pharmacy, University of Istanbul, 34452 Universite, Istanbul, Turkey.

Aloe vera (L.) Burm. fil. (= A. barbadensis Miller) (Liliaceae) is native to North Africa and also cultivated in Turkey. Aloes have long been used all over the world for their various medicinal properties. In the past 15 years, there have been controversial reports on the hypoglycaemic activity of Aloe species, probably due to differences in the parts of the plant used or to the model of diabetes chosen. In this study, separate experiments on three main groups of rats, namely, non-diabetic (ND), type I (IDDM) and type II (NIDDM) diabetic rats were carried out. A. vera leaf pulp and gel extracts were ineffective on lowering the blood sugar level of ND rats. A. vera leaf pulp extract showed hypoglycaemic activity on IDDM and NIDDM rats, the effectiveness being enhanced for type II diabetes in comparison with glibenclamide. On the contrary, A. vera leaf gel extract showed hyperglycaemic activity on NIDDM rats. It may therefore be concluded that the pulps of Aloe vera leaves devoid of the gel could be useful in the treatment of non-insulin dependent diabetes mellitus Copyright 2001 John Wiley & Sons, Ltd.
And more on diabetes models:

Hypoglycemic effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats.

Rajasekaran S, Sivagnanam K, Ravi K, Subramanian S.

Department of Biochemistry & Molecular Biology, University of Madras, Chennai, Tamil Nadu, India.

In the present study an attempt has been made to evaluate the presence of hypoglycemic activity in the alcoholic extract of Aloe vera gel. Effects of oral administration of A. vera extract at a concentration of 200 and 300 mg/kg of body weight on (a) normal fasted rats, (b) oral glucose-loaded rats, and (c) streptozotocin-induced diabetic rats have been studied. A. vera extract maintain the glucose homeostasis by controlling the carbohydrate metabolizing enzymes.

Another experimental model to clarify the mechanism of glucose control by aloe:

Effect of aloes on blood glucose levels in normal and alloxan diabetic mice.

Ajabnoor MA.

Department of Clinical Biochemistry, College of Medicine and Allied Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

The acute and chronic effects of the exudate of Aloe barbadensis leaves and its bitter principle were studied on plasma glucose levels of alloxan-diabetic mice. Aloes was administered orally, 500 mg/kg, and the bitter principle was administered intraperitoneally, 5 mg/kg. The hypoglycemic effect of a single oral dose of aloes on serum glucose level was insignificant whereas that of the bitter principle was very highly significant and extended over a period of 24 h with maximum hypoglycemia observed at +8 h. In chronic studies, aloes was administered twice daily and the bitter principle was administered once a day for 4 days. The maximum reduction in plasma glucose level was observed at the 5th day in both cases. The hypoglycemic effect of aloes and its bitter principle may be mediated through stimulating synthesis and/or release of insulin from the beta-cells of Langerhans.
A recent review of supplements in treating diabetes touts aloe as one of the few that in multiple studies show positive results in controlling blood sugar:

 
Systematic review of herbs and dietary supplements for glycemic control in diabetes.

Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS.

Division for Research and Education in Complementary and Integrative Medical Therapies, Harvard Medical School, Boston, Massachusetts, USA. gyeh@caregroup.harvard.edu

OBJECTIVE: To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale. RESULTS: A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. CONCLUSIONS: There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.
Here is a fascinating finding about aloe and the neurodegenerative consequences of diabetes that affect memory, various behaviors, and learning abilities in a diabetic mouse model.  Again relevance to human biology is suggestive, but not proven.

 
Susceptibility of hippocampus and cerebral cortex to oxidative damage in streptozotocin treated mice: prevention by extracts of Withania somnifera and Aloe vera.

Parihar MS, Chaudhary M, Shetty R, Hemnani T.

Biochemistry Division, Faculty of Life Science, School of Studies in Zoology, Vikram University, Ujjain 456 010, India.

Diabetes mellitus is reported to impair the memory function in experimental animals. Since the mammalian hippocampus and cerebral cortex play a pivotal role in a diverse set of cognitive functions, such as novelty detection and memory, we examined the vulnerability of cortex and hippocampus regions of the brain to oxidative damage in streptozotocin (STZ) diabetic mice. We next examined the attenuating effect of extracts of Withania somnifera and Aloe vera on prevention of hippocampal and cortical cell degenerations. Doses of both plant extracts given to experimental animals were based on the evaluation of their total antioxidant activity and also their potency to reduce Fe(3+). We assayed lipid peroxidation (LPO) and protein carbonyl (PC) in both regions of the brain and observed the changes in memory and motor behavioral functions in diabetic and control mice. The results showed a significant ( [Formula: see text] ) increase in LPO and PC in hippocampus and cortical regions of STZ diabetic mice. We also found a significant impairment in both motor and memory behavioral functions in diabetic mice. However, when diabetic mice were supplemented with the extracts of Withania somnifera and Aloe vera, the oxidative damage in both brain regions was reduced as marked by a significant ( [Formula: see text] ) declines in both LPO and PC. The combination of extracts of Withania somnifera and Aloe vera was more effective in reducing oxidative damage in brain regions than the supplementation of single plant extract. The combination also lowered the blood glucose level in comparison to STZ diabetic mice. Memory impairment and motor dysfunction were also improved by the plant extracts supplementation. We conclude that impairments in the hippocampus and cortex in STZ diabetic mice are associated with an increased free radical mediated oxidative damage and that the supplementation of plant extracts showed preventive effects in attenuating oxidative damage in both brain regions possibly via antioxidative mechanisms.
Antihypertensive properties
Blood pressure control may also be an attribute of aloe.

 
Hypotensive effect of chemical constituents from Aloe barbadensis.

Saleem R, Faizi S, Siddiqui BS, Ahmed M, Hussain SA, Qazi A, Dar A, Ahmad SI, Qazi MH, Akhtar S, Hasnain SN.

Dr. H.M.I. Institute of Pharmacology and Herbal Sciences, Hamdard University, Karachi, Pakistan. rs127pk@yahoo.com

Hypotensive effects of aloeemodin, aloin A, elgonica dimer A and bisbenzopyran from Aloe barbadensis have been studied. Aloeemodin has emerged as a potent hypotensive agent in current pharmacological investigations and caused 26 %, 52 %, and 79 % falls in mean arterial blood pressure at the corresponding doses of 0.5, 1, and 3 mg/kg in rats. The paper also describes the absolute configuration of elgonica dimer A (1).
Antioxidant properties relating to anti-atherogenesis

Note that in 1985 when the above observations were made, the knowledge contained in this Library about all the various compounds within aloe was not known.  This Library has the advantage of hindsight. We can emphasize the findings in the above 1985 study to connect the dots of what we now know about lipid peroxidation, superoxide formation, oxygen and nitrogen free radicals, and their production of inflammation. Now we know that the inner lining of critical blood vessels, when inflamed, stimulates the collection of these lipid products and calcium and promotes inflammatory responses, which ultimately create the plaque.

The following study suggests a role for lifelong aloe supplementation as a cardioprotective agent based upon its intra-hepatic (inside the liver) cholesterol-lowering ability as well as its antioxidant properties.

Efficacy of dietary aloe vera supplementation on hepatic cholesterol and oxidative status in aged rats.

Lim BO, Seong NS, Choue RW, Kim JD, Lee HY, Kim SY, Yu BP, Jeon TI, Park DK.

Graduate School of East-West Medical Science, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-Ku, Korea. beongou@khu.ac.kr

In the current study, we show the anti-oxidative and hypocholesterol effects of aloe vera in the liver. Male specific pathogen-free (SPF) Fischer 344 rats were randomly assigned to one of four groups: Group A (control) was fed test chow without aloe supplementation; Group B was fed a diet containing a 1% (per weight basis) freeze-dried aloe filet; Group C was fed a diet containing a 1% (per weight basis) charcoal-processed, freeze-dried aloe filet; and Group D was fed a diet containing a charcoal-processed freeze-dried, whole leaf aloe (0.02% per weight basis) in the drinking water. Our results show that a life-long intake of aloe had superior anti-oxidative action against lipid peroxidation in vivo, as indicated by reduced levels of hepatic phosphatidylcholine hydroperoxide. Additional anti-oxidative action was evidenced by enhanced superoxide dismutase (SOD) and catalase activity in groups B and C. Furthermore, our study revealed that hepatic cholesterol significantly increased in the control group during aging in contrast to the aloe-supplemented groups, which showed approximately 30% lower cholesterol levels, thereby an effective hypocholesteremic efficacy. In this report, we suggest that life-long dietary aloe supplementation suppresses free radical-induced oxidative damage and age-related increases in hepatic cholesterol.
Both enhanced lipid peroxidation and microvascular disease leads to kidney damage and renal failure in type 2 diabetes. The following abstract shows how aloe’s antioxidant properties can account for the ability to protect kidney tissue from damage in the diabetic rat model.

Effect of Aloe vera (L.) Burm. fil. leaf gel and pulp extracts on kidney in type-II diabetic rat models.

Bolkent S, Akev N, Ozsoy N, Sengezer-Inceli M, Can A, Alper O, Yanardag R.

Department of Biology, Faculty of Science, Istanbul University, 34459-Vezneciler, Istanbul, Turkey.

Significant degenerative changes were observed in the kidney tissue of untreated neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. These degenerative changes were diminished in the kidney tissue of diabetic animals given glibenclamide and Aloe leaf gel and pulp extracts. Kidney lipid peroxidation levels were increased in diabetic rats compared to healthy rats; these levels were higher in rats treated with glibenclamide than in those which received Aloe extracts. Serum urea and creatinine levels were higher in diabetic rats in comparison to healthy rats. The administration of Aloe gel extract and glibenclamide decreased serum urea and creatinine levels in comparison to diabetic controls. Only A. vera leaf gel extract showed improvement both in histological and biochemical parameters suggesting a protective effect of A. vera

Antibacterial / antiviral / antifungal / antiparasitic properties
More than a decade has passed since H. pylori, the cause of bacterial infections of the stomach, was recognized as a possible cause of chronic gastritis and recurrent peptic ulcer disease. Aloe now is recognized as an effective treatment for H. pylori infections since it can inhibit the growth of this pathogen.  The general antibiotic potential of aloe is also suggested.
 

Aloe-emodin effects on arylamine N-acetyltransferase activity in the bacterium Helicobacter pylori.

Wang HH, Chung JG, Ho CC, Wu LT, Chang SH.

Arylamine N-acetyltransferase (NAT) activities with p-aminobenzoic acid (PABA) and 2-aminofluorene (AF) were determined in H. pylori collected from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without different concentrations of aloe-emodin co-treatment showed different percentages of AF and PABA acetylation. The data indicate that there was decreased NAT activity associated with increased aloe-emodin in H. pylori cytosols. Inhibition of growth study from H. pylori demonstrated that aloe-emodin elicited dose-dependent growth inhibition in H. pylori cultures. The report is the first finding of aloe-emodin inhibition of arylamine NAT activity in a strain of H. pylori.
The structural and functional similarities of aloe to tetracyclines may explain the bacteriostatic properties of aloe.

 
Inhibition of collagenase and metalloproteinases by aloins and aloe gel.

Barrantes E, Guinea M.

Department of Pharmacology, School of Pharmacy, University of Alcala, Ctra. Madrid-Barcelona Km 33.6, 28871 Alcala de Henares, Spain.

The effects of Aloe barbadensis gel and aloe gel constituents on the activity of microbial and human metalloproteinases have been investigated. Clostridium histolyticum collagenase (ChC) results dose-dependently inhibited by aloe gel and the activity-guided fractionation led to an active fraction enriched in phenolics and aloins. Aloins have been shown to be able to bind and to inhibit ChC reversibly and non-competitively. Aloe gel and aloins are also effective inhibitors of stimulated granulocyte matrix metalloproteinases (MMPs). The remarkable structural resemblances between aloins and the pharmacophore structure of inhibitory tetracyclines, suggest that the inhibitory effects of aloins are via an interaction between the carbonyl group at C(9) and an adjacent hydroxyl group of anthrone (C(1) or C(8)) at the secondary binding site of enzyme, destabilizing the structure of granulocyte MMPs.
The inner gel of aloe is effective for two more pathogens described below.

 
In vitro susceptibilities of Shigella flexneri and Streptococcus pyogenes to inner gel of Aloe barbadensis Miller.

Ferro VA, Bradbury F, Cameron P, Shakir E, Rahman SR, Stimson WH.

Department of Immunology, University of Strathclyde, Glasgow G4 ONR, United Kingdom. v.a.ferro@strath.ac.uk

Aloe barbadensis Miller (or Aloe vera) has widespread use in health products, and despite numerous reports on the whole plant, little work has been performed on the inner gel, which has been used extensively in these products. This report describes the in vitro susceptibilities of two bacteria to this component.

The mechanisms of antibiotic activity of aloe based on two of the anthraquinones, aloin and aloe emodin:

[Relationship between antibacterial activity of aloe and its anthaquinone compounds]

[Abstract in Chinese]

Tian B, Hua YJ, Ma XQ, Wang GL.

Department of Applied Bioscience, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029, Zhejiang, China. tianbing@zju.edu.cn

OBJECTIVE: To investigate the relationship between the antibacterial activity of aloe and its contents of anthaquinone compounds, measure and compare antibacterial activities of aloin and aloe-emodin, and analyse the effect of glycoside on the antibacterial activity of aloin. METHOD: The antibacterial activities of the extracts from the outer leaf of Aloe saponaria Haw, aloin and aloe-emodin against three Gram-negative and two Gram-positive bacteria were investigated with the method of agar diffusion. The antibacterial effect of aloin on E. coli was further studied with scanning electron microscopy. RESULT: The antibacterial activities of aloe showed to be dependent on the dose of anthraquinone, aloin (1 g x L(-1)) exhibited higher antibacterial activity [inhibition diameter > (7. 1 +/- 0.15) mm] than Aloe-emodin (inhibition diameter < 5.0 mm), and aloin changed the morphology of E. coli and damaged the outer cell structure. CONCLUSION: Anthraquinone compounds are the active antibacterial components in aloe and aloin is the main active compound. The glycoside makes it easy for aloin to invade cells and enhances its activity.
Antiviral properties of aloe, due to its content of anthraquinones, are discussed in the following study.

Inactivation of enveloped viruses by anthraquinones extracted from plants.

Sydiskis RJ, Owen DG, Lohr JL, Rosler KH, Blomster RN.

Department of Microbiology, University of Maryland, Baltimore 21201.

To determine the extent of antiviral activity present in a number of plant extracts, hot glycerin extracts were prepared from Rheum officinale, Aloe barbadensis, Rhamnus frangula, Rhamnus purshianus, and Cassia angustifolia and their virucidal effects were tested against herpes simplex virus type 1. All the plant extracts inactivated the virus. The active components in these plants were separated by thin-layer chromatography and identified as anthraquinones. A purified sample of aloe emodin was prepared from aloin, and its effects on the infectivity of herpes simplex virus type 1 and type 2, varicella-zoster virus, pseudorabies virus, influenza virus, adenovirus, and rhinovirus were tested by mixing virus with dilutions of aloe emodin for 15 min at 37 degrees C, immediately diluting the sample, and assaying the amount of infectious virus remaining in the sample. The results showed that aloe emodin inactivated all of the viruses tested except adenovirus and rhinovirus. Electron microscopic examination of anthraquinone-treated herpes simplex virus demonstrated that the envelopes were partially disrupted. These results show that anthraquinones extracted from a variety of plants are directly virucidal to enveloped viruses.
This next abstract deals with the inhibition by aloe of Newcastle disease, a viral infection of chickens and other birds.

 
Evaluation of the efficacy of the crude extract of Aloe secundiflora in chickens experimentally infected with Newcastle disease virus.

Waihenya RK, Mtambo MM, Nkwengulila G.

Department of Zoology and Marine Biology, University of Dar es Salaam, PO Box 35064, Dar es Salaam, Tanzania.

Two replicate experiments were carried out to verify the efficacy of Aloe species (Aloaceae) as used for the control of Newcastle disease (ND) in rural poultry in free-range systems among several communities in Tanzania. Four months old local chickens free of Newcastle disease antibodies were used. Following inoculation with ND virus, body weights, clinical signs, antibody levels and mortality were monitored. Results showed that there was reduced mortality rate and the severity of clinical signs during the acute phase of the infection in Aloe treated chickens compared with the non-treated ones. However, there was no significant effect of the Aloe on the antibody levels that were attributed to the recovery of the surviving chickens. The findings of this study suggest that Aloe secundiflora could be a potential candidate on the management of Newcastle disease in chickens. Further studies are in progress to identify the active ingredients of A. secundiflora against Newcastle disease virus.

Antifungal use for aloe based upon the following:

 
Antifungal effects of different plant extracts and their major components of selected aloe species.

Ali MI, Shalaby NM, Elgamal MH, Mousa AS.

Botany Department, Faculty of Science, Cairo University, Giza 12613, Egypt.

Different extracts of both fresh and dry leaves of Aloe eru A. Berger, A. vera L. Webb & Berth and A. arborescens Mill. were screened for their antifungal activity against Aspergillus niger, Cladosporium herbarum and Fusarium moniliforme. The toxicity of the isolated pure components was evaluated on the tested fungi. A comparative chromatographic study was performed to differentiate between natural components existing in various fractions and extracts of Aloe species and specific spray reagents were used for the detection of anthraquinones in the isolated components. Copyright 1999 John Wiley & Sons, Ltd.

More on antifungal properties:

Effect of Leaf Extracts of Aloe arborescens Mill subsp. natalensis Berger on Growth of Trichophyton mentagrophytes
Keisuke Fujita,1 Yasuo Yamada,2 Keizou Azuma,2 and Susumu Hirozawa2
1Institute of Pharmacognosy, Fujita-Gakuen University, Hisai, Mie 514-12, Japan
2Department of Microbiology, School of Health Sciences, Fujita-Gakuen University, Toyoake, Aichi 470-11, Japan
Abstract
The antifungal activity of a lyophilized powder containing aloe leaf homogenate (whole-leaf powder) against Trichophyton mentagrophytes was investigated. The minimal inhibitory concentration was 25 mg/ml by the agar dilution method, using Sabouraud glucose agar medium. At subinhibitory concentrations, the powder exerted its main effect on colony growth by prolongation of the lag phase and inhibition of growth rate. Homogenates of fresh whole leaf were filtered through Whatman GF/A paper, and the filtrate was dialyzed and concentrated by molecular filtration using an Amicon hollow-fiber dialyzer concentrator DC-2, and a powder containing components with molecular weights higher than 10,000 (high-molecular-weight component powder) was prepared by lyophilization. The minimal inhibitory concentrations against three strains of T. mentagrophytes were all 10 mg/ml. The inhibitory activity was fungicidal and was lost by heating at 100°C for 30 min. Both the whole-leaf powder and the high-molecular-weight component powder induced various morphological abnormalities in spores and hyphae by the inhibition of spore germination and development of hyphae.
There is an antiparasitic application for aloe based upon the next study of the parasite Trichomonas vaginalis, the cause of a sexually transmitted disease, an often severe vaginitis that can become indolent and chronic, such that male partners may become asymptomatic infected carriers or become symptomatic with a painful urethritis. 

[The action of an aqueous extract of Aloe barbadensis Miller in an in-vitro culture of Trichomonas vaginalis]

[Abstract in Spanish]

Rojas L, Matamoros M, Garrido N, Finlay C.

Instituto de Medicina Tropical Pedro Kouri.

The antiparasitic action of an aqueous extract of Aloe barbadensis Miller against and in vitro culture of Trichomonas vaginalis was studied for the first time. Three strains of this parasite were used for the study. Taking an initial concentration of 400 mg/mL of the extract, double serial dilutions were performed, and final concentrations based on the dried weight of the extract were 10.4, 20.8, 41, 83, and 160 mg/mL. Within 24 hours, percentages of inhibition greater than 50% were obtained from concentrations of 20.8 micrograms/mL. Similar results were obtained at 48, and 72 hours, with a lower concentration, the inhibition of growth was greater than 50%.

Another cautionary abstract follows regarding photocytotoxicity in human fibroblasts treated with aloe ingredients.  This was found only in tissue culture.

 
In vitro studies on the photobiological properties of aloe emodin and aloin A.

Wamer WG, Vath P, Falvey DE.

Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD 20740, USA. wwarmer@cfsan.fda.gov

Plants containing aloin A, aloe emodin, and structurally related anthraquinones have long been used as traditional medicines and in the formulation of retail products such as laxatives, dietary supplements, and cosmetics. Since a recent study indicated that topically applied aloe emodin increases the sensitivity of skin to UV light, we examined the events following photoexcitation of aloin A and aloe emodin. We determined that incubation of human skin fibroblasts with 20 microM aloe emodin for 18 h followed by irradiation with UV or visible light resulted in significant photocytotoxicity. This photocytotoxicity was accompanied by oxidative damage in both cellular DNA and RNA. In contrast, no photocytotoxicity was observed following incubation with up to 500 microM aloin A and irradiation with UVA light. In an attempt to explain the different photobiological properties of aloin A and aloe emodin, laser flash photolysis experiments were performed. We determined that the triplet state of aloe emodin was readily formed following photoexcitation. However, no transient intermediates were formed following photoexcitation of aloin A. Therefore, generation of reactive oxygen species and oxidative damage after irradiation of aloin A is unlikely. Although aloin A was not directly photocytotoxic, we found that human skin fibroblasts can metabolize aloin A to aloe emodin.
Promoter of chemical and drug detoxification of liver

Aloe facilitates detoxification providing chemoprotection against carcinogens and other toxins, including drugs.

Chemomodulatory action of Aloe vera on the profiles of enzymes associated with carcinogen metabolism and antioxidant status regulation in mice.

Singh RP, Dhanalakshmi S, Rao AR.

Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

The effect of two doses (30 microl and 60 microl/day/mice daily for 14 days) of the fresh leaf pulp extract of Aloe vera was examined on carcinogen-metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of mice. The modulatory effect of the pulp extract was also examined on extrahepatic organs (lung, kidney and forestomach) for the activities of glutathione S-transferase, DT-diophorase, superoxide dismutase and catalase. The positive control mice were treated with butylated hydroxyanisole (BHA). Significant increases in the levels of acid soluble sulfhydryl (-SH) content, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase (GR) were observed in the liver. Aloe vera significantly reduced the levels of cytochrome P450 and cytochrome b5. Thus, Aloe vera is clearly an inducer of phase-II enzyme system. Treatment with both doses of Aloe caused a decrease in malondialdehyde (MDA) formation and the activity of lactate dehydrogenase in the liver, suggesting its role in protection against prooxidant-induced membrane and cellular damage. The microsomal and cytosolic protein was significantly enhanced by Aloe vera, indicating the possibility of its involvement in the induction of protein synthesis. BHA, an antioxidant compound, provided the authenticity of our assay protocol and response of animals against modulator. The pulp extract was effective in inducing GST, DTD, SOD and catalase as measured in extrahepatic organs. Thus, besides liver, other organs (lung, kidney and forestomach) were also influenced favorably by Aloe vera in order to detoxify reactive metabolites, including chemical carcinogens and drugs.
Potential additional treatment for autoimmune gastrointestinal inflammatory diseases and duodenal and gastric ulcers

Aloe is not only anti-inflammatory for skin, but in the following abstract we see the emergence of the anti-inflammatory benefits to inflammatory bowel diseases such as ulcerative colitis and regional enteritis (Crohn’s disease).

 
Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro.

Langmead L, Makins RJ, Rampton DS.

Centre for Adult and Paediatric Gastroenterology, Institute of Cellular and Molecular Science, Barts and the London, Queen Mary School of Medicine and Dentistry, London, UK.

BACKGROUND: Oral aloe vera gel is widely used by patients with inflammatory bowel disease and is under therapeutic evaluation for this condition. AIM: To assess the effects of aloe vera in vitro on the production of reactive oxygen metabolites, eicosanoids and interleukin-8, all of which may be pathogenic in inflammatory bowel disease. METHODS: The anti-oxidant activity of aloe vera was assessed in two cell-free, radical-generating systems and by the chemiluminescence of incubated colorectal mucosal biopsies. Eicosanoid production by biopsies and interleukin-8 release by CaCo2 epithelial cells in the presence of aloe vera were measured by enzyme-linked immunosorbent assay. RESULTS: Aloe vera gel had a dose-dependent inhibitory effect on reactive oxygen metabolite production; 50% inhibition occurred at 1 in 1000 dilution in the phycoerythrin assay and at 1 in 10-50 dilution with biopsies. Aloe vera inhibited the production of prostaglandin E2 by 30% at 1 in 50 dilution (P = 0.03), but had no effect on thromboxane B2 production. The release of interleukin-8 by CaCo2 cells fell by 20% (P < 0.05) with aloe vera diluted at 1 in 100, but not at 1 in 10 or 1 in 1000 dilutions. CONCLUSION: The anti-inflammatory actions of aloe vera gel in vitro provide support for the proposal that it may have a therapeutic effect in inflammatory bowel disease.
Read what happened in this formal, very-well-designed human study of ulcerative colitis patients:

 
Randomized, double-blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis.

Langmead L, Feakins RM, Goldthorpe S, Holt H, Tsironi E, De Silva A, Jewell DP, Rampton DS.

Centre for Gastroenterology, Institute of Cellular and Molecular Science, Barts and The London, Queen Mary School of Medicine and Dentistry, London, UK.

BACKGROUND: The herbal preparation, aloe vera, has been claimed to have anti-inflammatory effects and, despite a lack of evidence of its therapeutic efficacy, is widely used by patients with inflammatory bowel disease. AIM: To perform a double-blind, randomized, placebo-controlled trial of the efficacy and safety of aloe vera gel for the treatment of mildly to moderately active ulcerative colitis. METHODS: Forty-four evaluable hospital out-patients were randomly given oral aloe vera gel or placebo, 100 mL twice daily for 4 weeks, in a 2 : 1 ratio. The primary outcome measures were clinical remission (Simple Clinical Colitis Activity Index </= 2), sigmoidoscopic remission (Baron score </= 1) and histological remission (Saverymuttu score </= 1). Secondary outcome measures included changes in the Simple Clinical Colitis Activity Index (improvement was defined as a decrease of >/= 3 points; response was defined as remission or improvement), Baron score, histology score, haemoglobin, platelet count, erythrocyte sedimentation rate, C-reactive protein and albumin. RESULTS: Clinical remission, improvement and response occurred in nine (30%), 11 (37%) and 14 (47%), respectively, of 30 patients given aloe vera, compared with one (7%) [P = 0.09; odds ratio, 5.6 (0.6-49)], one (7%) [P = 0.06; odds ratio, 7.5 (0.9-66)] and two (14%) [P < 0.05; odds ratio, 5.3 (1.0-27)], respectively, of 14 patients taking placebo. The Simple Clinical Colitis Activity Index and histological scores decreased significantly during treatment with aloe vera (P = 0.01 and P = 0.03, respectively), but not with placebo. Sigmoidoscopic scores and laboratory variables showed no significant differences between aloe vera and placebo. Adverse events were minor and similar in both groups of patients. CONCLUSION: Oral aloe vera taken for 4 weeks produced a clinical response more often than placebo; it also reduced the histological disease activity and appeared to be safe. Further evaluation of the therapeutic potential of aloe vera gel in inflammatory bowel disease is needed.

Reporting a year earlier on ulcerative colitis and possible mechanisms of aloe intervention for healing and protection:

 
The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats.

Kokkinos L, Suprun M, Petrova A, Mikhal'chik E, Luci A, De Luca C.

Department of Molecular Biology, Russian State Medical University, Ostrovityanova 1, Moscow 117513, Russia. korkin@aha.ru

Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane [dextran] sulfate (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment.
The above study suggests that the mechanism is such that pretreatment, which in human terms means prevention in nature, should be considered in patients with strong family histories of ulcerative colitis but who have not yet exhibited symptoms.

Also relating to gastritis and peptic ulcer conditions, the following suggests aloe may be an acid reducer like the drugs Zantac®, Pepcid®, and Tagamet®. Its use as a remedy for GI ailments is substantiated by the abstract below.

Use for injury to the stomach, esophagus, or duodenum from too much acid, which leads to gastritis, esophagitis, or ulcers, is suggested next.

 
The effect of Aloe vera A. Berger (Liliaceae) on gastric acid secretion and acute gastric mucosal injury in rats.

Yusuf S, Agunu A, Diana M.

Department of Human Physiology, Ahmadu Bello University, Zaria, Nigeria. sadiqyusuf@yahoo.com

The effect of varying doses of ethanol extract of Aloe vera (Liliaceae) on acute gastric mucosal lesions induced by 0.6 M HCl and acid output was studied in the pylorus ligated and lumen perfuse rats, respectively. Acid secretion was determined by titration of the collected gastric juice to pH 7.0. Intraperitoneal injection of Aloe vera, dose dependently inhibited gastric acid secretion. [Editor’s note: not an effect induced by topical contact with injured mucosa] The plant was more active as a gastroprotective agent at lower concentration against mucosal injury induced by 0.6 M HCl. In conclusion, Aloe vera is endowed with gastric acid anti-secretory activity and could protect the gastric mucosa at low concentrations against injurious agents.
Managing psoriasis

Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study.

Syed TA, Ahmad SA, Holt AH, Ahmad SA, Ahmad SH, Afzal M.

Department of Clinical Physiology, Malmo University Hospital, Sweden.

The purpose of this double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerability of topical Aloe vera extract 0.5% in a hydrophilic cream to cure patients with psoriasis vulgaris. Sixty patients (36M/24F) aged 18-50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 4.8 and 16.7 (mean 9.3) were enrolled and randomized to two parallel groups. The mean duration of the disease prior to enrollment was 8.5 years (range 1-21). Patients were provided with a precoded 100g tube, placebo or active (with 0.5% Aloe vera extract), and they self-administered trial medication topically (without occlusion) at home 3 times daily for 5 consecutive days per week (maximum 4 weeks active treatment). Patients were examined on a weekly basis and those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. The treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. By the end of the study, the Aloe vera extract cream had cured 25/30 patients (83.3%) compared to the placebo cure rate of 2/30 (6.6%) (P < 0.001) resulting in significant clearing of the psoriatic plaques (328/396 (82.8%) vs placebo 28/366 (7.7%), P < 0.001) and a decreased PASI score to a mean of 2.2. The findings of this study suggest that topically applied Aloe vera extract 0.5% in a hydrophilic cream is more effective than placebo, and has not shown toxic or any other objective side-effects. Therefore, the regimen can be considered a safe and alternative treatment to cure patients suffering from psoriasis.
Cathartic properties

Among the first discovered uses for Aloe vera was its efficacy as a cathartic.  Note: Barbaloin is from the Aloe plant.

Studies of aloe. IV. Mechanism of cathartic effect. (3).

Ishii Y, Tanizawa H, Takino Y.

School of Pharmaceutical Sciences, University of Shizuoka, Japan.

Charcoal transport, as an indicator of the degree of peristalsis, and water content in the large intestine after the intracaecal administration of barbaloin, were measured simultaneously in the same rat. Charcoal transport was significantly accelerated at both 3.5 and 6.5 h after the administration of barbaloin. At 6.5 h, diarrhea instead of normal faeces was observed. Moreover, at 1 h before the acceleration of charcoal transport, a marked increase in the relative water content of the large intestine was observed. It appears that the increase in water content of the large intestine induced by barbaloin precedes the stimulation of peristalsis, attended by diarrhea. Therefore, it is suggested that the increase in water content is a more important factor than the stimulation of peristalsis in the diarrhea induced by barbaloin.
More on constipation relief:

A double-blind trial of a celandin, aloevera and psyllium laxative preparation in adult patients with constipation.

Odes HS, Madar Z.

Intestinal Diseases Unit, Soroka Medical Center, Beer Sheva, Israel.

The aim of this study was to evaluate the effect of a novel laxative preparation, composed of celandin, aloevera and psyllium in patients with chronic constipation. Thirty-five men and women were randomized to receive capsules containing celandin-aloevera-psyllium, or placebo, in a double-blind trial lasting 28 days. Symptoms in the last 2 weeks of the treatment period were compared to those in the 14-day pre-trial basal period. In the celandin, aloevera and psyllium group, bowel movements became more frequent, the stools were softer and laxative dependence was reduced. In the placebo group, all these parameters were unchanged. Abdominal pain was not reduced in either group. The results of this study show that the preparation is an effective laxative in the treatment of constipation.
On the mechanism of the cathartic effect of aloe components:

Studies of aloe. III. Mechanism of cathartic effect. (2).

Ishii Y, Tanizawa H, Takino Y.

School of Pharmaceutical Sciences, University of Shizuoka, Japan.

The mechanism of action of aloe-emodin-9-anthrone, a decomposition product of barbaloin, in causing a significant increase in the water content of the rat large intestine, was investigated. Aloe-emodin-9-anthrone inhibited rat colonic Na+, K(+)-adenosine triphosphatase (ATPase) in vitro, and increased the paracellular permeability across the rat colonic mucosa in vivo. Therefore, it seemed that the increase in water content of the rat large intestine produced by aloe-emodin-9-anthrone was due to both inhibition of absorption and stimulation of secretion without stimulation of peristalsis. Furthermore, pretreatment with loperamide, an antidiarrheal agent, completely prevented the increase of paracellular permeability induced by aloe-emodin-9-anthrone but did not completely reduce the concomitant increase in residual fluid volume. These findings suggest that aloe-emodin-9-anthrone has multiple mechanisms of action involved in the increase of water content in the rat large intestine.
Stimulates hematopoiesis
More immunopharmacological studies, exemplied by the following abstract, reveal that the hematopoietic (blood cell producing) effects come from a particular fraction of the aloe gel, which further elucidates the multiplicity of pharmacologically active compounds within this plant genus.

 
Fractionation of Aloe vera L. inner gel, purification and molecular

profiling of activity.

Talmadge J, Chavez J, Jacobs L, Munger C, Chinnah T, Chow JT, Williamson D, Yates K.

Laboratory of Transplantation Immunology, Department of Pathology and Microbiology, University of Nebraska Medical Center, 987660 Nebraska Medical Center, South 42nd Street, Omaha, NE 68198-7660, USA. jtalmadg@unmc.edu

Products derived from the inner gel of the Aloe vera L. plant have demonstrated multiple clinical activities, and are used routinely to accelerate wound healing. However, typical of natural products, the complex nature of Aloe vera gels may contribute to diverse pharmacologic activities. Our focus on the hematopoietic activities of Aloe vera extracts is extended by these functional studies, which used purified fractions from Aloe vera gel and included a preliminary organ-specific in vitro molecular profile. Studies using a >99% pure carbohydrate fraction from Aloe vera extracts revealed increased hematopoietic and hematologic activity compared to the starting material. In addition, this fraction differentially regulated liver and lung cytokine mRNA levels, resulting in significant increases in message for hematopoietic cytokines [granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF)]. This profile of activity differed from another fraction obtained from Aloe vera, suggesting the potential for diverse pharmacologic activity. The molecular studies were undertaken using co-cultures of organ slices to limit the amount of purified material required. In summary, these studies revealed significant hematopoietic activity by both pharmacologic and molecular analysis using a >99% pure carbohydrate fraction from Aloe vera gels.
Analgesic properties
One of the cardinal features of inflammation is pain.  In addition to aloe being a proven anti-inflammatory agent, it is an analgesic as well.  The following  abstract gives a possible neurophysiological explanation of how aloe works to relieve pain.  The study also demonstrates a possible mechanism for the analgesic effect of aloe in inflammatory conditions.  This paper uses an electrophysiological study of end plate (nerve ending) potentials in a neurophysiological model using crayfish neuromuscular junctions (where the nerves activating muscles meet the muscle cells).

 
Initial characterization of the effects of Aloe vera at a crayfish neuromuscular junction.

Friedman RN, Si K.

Section of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202-5112, USA. rfriedma@iupui.edu

This study examines the effects of Aloe vera on neurotransmission processes in a well-established invertebrate neuromuscular junction preparation. We studied concentration-response relationships of an Aloe vera extract on excitatory junctional potentials (EJPs) at the opener muscle of the dactyl in the first and second walking limbs of crayfish (Procambarus clarkii and simulans). We observed concentration-dependent depolarizations of the muscle fibre membrane resting potential, depression of EJP amplitudes and an increase in latency to onset of the EJP following electrical stimulation of the isolated excitatory axon in the meropodite. These effects occurred with Aloe concentrations within the 1%-10% (wt-vol) range. Effects of lower concentrations, ranging to a minimum of 0.01% were equivocal. The effects of Aloe were at least partially, and in a majority of cases totally, reversible. EJPs reduced by Aloe could be restored by increasing the nerve stimulation amplitude. This, along with the latency increase, suggests a depression of action potential generation and conduction. The results provide a preliminary characterization of the effects of Aloe vera on the neurotransmission process and suggest that these effects may at least partially account for Aloe's analgesic and antiinflammatory effects. This study shows that the crayfish NMJ preparation should be useful for further elucidating the location(s) and mechanism(s) of action of Aloe on the nervous system. Copyright 1999 John Wiley & Sons, Ltd.
Spermicidal contraceptive
A study suggests the possible combination of aloe and zinc acetate as a nonirritating vaginal spermicidal contraceptive:

 
Zinc acetate and lyophilized aloe barbadensis as vaginal contraceptive.

Fahim MS, Wang M.

Center of Reproductive Science and Technology, School of Medicine, University of Missouri, Columbia 65212, USA.

Twenty samples of fresh ejaculate, donated by healthy volunteers ranging in age from 20-30 years, were obtained from the Center for Fertility & Cryobiology, University of Missouri, Columbia, Missouri. Average semen volume was 2.49 ml; average sperm motility was 71.32%; and average sperm density was 113.71 x 10(6) /ml. Testing for spermicidal effectiveness of a 1% concentration of zinc acetate, zinc sulfate, zinc chloride, and zinc gluconate proved that only zinc acetate was spermicidal. It appears this is due to the acetate in zinc acetate which may decrease oxygen utilization by sperm. Zinc acetate in vitro was antiviral while lyophilized aloe barbadensis was not. Lyophilized aloe barbadensis at concentrations of 7.5% and 10% proved to be spermicidal due to the multiple micro elements (boron, barium, calcium, chromium, copper, iron, potassium, magnesium, manganese, phosphorus, and zinc) which were toxic to the tail causing instant immobilization. The two compounds did not irritate or cause ulceration of rabbit vaginal epithelium. These results suggest the possibility of using zinc acetate and lyophilized aloe barbadensis as a new, effective and safe vaginal contraceptive.
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Agronomic information pertaining to variance of active compounds based upon geographical origin of aloe plants considered

Geographical variation in the major compounds of Aloe ferox leaf exudate.

van Wyk BE, van Rheede van Oudtshoorn MC, Smith GF.

Department of Botany, Rand Afrikaans University, Johannesburg, South Africa.

Geographical variation in fresh Aloe ferox leaf exudate of which the dried product is commercially known as Cape Aloes, was investigated throughout the natural distribution range of the species. The composition of the major compounds is remarkably invariable, with aloeresin A, aloesin, and aloin (both epimers A and B) contributing between 70% and 97% of total dry weight, in a ratio of approximately 4:3:2, respectively. Minor compounds are less evenly distributed, with aloinoside A and aloinoside B more frequent in the western parts of the distribution area and aloeresin C and 5-hydroxyaloin A generally present in small quantities throughout the distribution area. The aloin content of the exudate is clearly related to provenance but there are no distinct geographical discontinuities. The selection of high-yielding provenances, with total aloin levels above 25%, is recommended for commercial cultivation.