Aloe vera (L.) Burm.f.

Last updated: 8 December 2014

Scientific Name

Aloe vera (L.) Burm.f.

Synonyms

Aloe barbadensis Mill., Aloe chinensis Steud. ex Baker, Aloe elongata Murray, Aloe flava Pers., Aloe indica Royle, Aloe lanzae Tod., Aloe maculata Forssk. [Illegitimate], Aloe rubescens DC., Aloe variegate Forssk. [Illegitimate], Aloe vulgaris Lam. [1]

Vernacular Name

 

Malaysia Lidah buaya (Peninsular); bunga raja raja (Sabah) [2]
English Barbados aloe, curaçao aloe, coastal aloe, Indian aloe, medicinal aloe, mediterranean aloe, true aloe, west indian aloe [2][3]
China Lu-hui [4]
India Kumari, ghikanuar, ghrit kumara [4]
Indonesia Lidah buaya [2]
Philippines Sabila (Tagalog); dilang-buwaya (Bikol); dilang-halo (Bisaya) [2]
Thailand Waan faimai (Northern); waan hang chorakhe, haang takhe (Central) [2][5]
Vietnam L[oo] h[ooj]i, l[uw] h[ooj]i, nha d[ar]m, cay aloe vera, cay lo hoi, cay nha dam [2][5]
Nepal Kunhur [4]
Sri Lanka Komarika [4]
Japan Aloe, feroxaroe [4][5]
Turkey Odagaci, sarisabir, sarysabyr [5]
Africa Aalwee, aalwyn [5]
France Aloes, aloes vulgaire, aloe vera [3][5]
Sweden Aloe, barbados aloe [5]
Poland Aloes, aloe vera, aloes de barbados, caraguata, erva-babosa, azehre vegetal [3]
Spain Aciber, aloe, flor do doserto, loto do deserto, linaloe, maguey morado, penca sabila, pitera amarelo, sabila do penca, savila, toots amarelo, zabila,zabila dos tos [5]
Russia Aloe, aloe nastojascee, aloe vera [5].

Geographical Distributions

The origin of Aloe vera is unknown [2][6] but some authors presumed that it is originated from Arabia, Somalia, Sudan or Oman [7]. This plant has been introduced and naturalized throughout most of the tropics, subtropics and warmer regions but will not grow in rainforest regions or dry deserts [6][7]. It can be found in most of Africa, Southern Arabia, Madagascar, West Indies and Bahamas, Southern USA, Mexico, Central America, Arabia, other parts of Asia [6] and Australia [7].

Botanical Description

A. vera is a plant from the family of Xanthorrhoeaceae [1]. It is a perennial shrub, 30-40 cm high [2].

The root is in the form of taproot, 5-10 cm long with abundant secondary root at the top of the soil. The root form a dense group and the secondary shoot that rise from the root gives rise to a new plant [2]. The stem is short [8].

The leaves is whether erect or slightly spreading, about 16 blades per plant, 40-50 cm x 6-7 cm in dimension, narrowly triangular, the upper surface greenish-grey to pale green together with spots and the lower blade usually lighter. The leave margin firm with minute deltoid pale teeth that measure 2 mm long. [2]

The inflorescence spike, simple and rarely branched, 60-100 cm tall, densely flowered with yellow, orange or red in colour. The anther and stigma is exserted. [2][8]

The fruit is in the form of capsule, ovoid and whitish green. The seed is numerous. [8]

Cultivation

No documentation.

Chemical Constituent

Aqueous extract of A. vera has been reported to containtriglucosylated naphthalene derivative (e.g. aloveroside A, aloveroside B) and phenyl pyrones (e.g. ρ-coumaroyl aloenin, aloenin B, 10-O-β-D-glucopyranosyl aloenin, aloenin-2′-ρ-coumaroyl ester, aloenin aglycone). [9][10][11][12]

Methanol extract of dried A. vera powder has been reported to contain chromones (e.g. chrysophanol, 7-hydroxy-2,5-dimethylchromone, saiko-chromone A, 5-((S)-2′-oxo-4′-hydroxypentyl)-2-hydroxymethylchromone, 5-((S)-2′-oxo-4′-hydroxypentyl)-2-(β-glucopyranosyl-oxy-methyl)-chromone, 5-(hydroxymethyl)-7-methoxy-2-methylchromone, 5-((4E)-2′-oxo-pentenyl)-2-hydroxymethylchromone, 7-hydroxy-5-(hydroxymethyl)-2-methylchromone, cinnamoyl-C-glycoside chromone, aloesin, 8-C-glucosyl-(R)-aloesol, 8-C-glucosyl-7-O-methyl-(S)-aloesol, and isoaloeresin D) and antraquinone (e.g. 10-hydroxyaloin A, 10-hydroxyaloin B, aloe-emodin, barbaloin/aloin A, isobarbaloin/aloin B). [9][11][12][13][14]

A. vera was also been reported to contain anthraquinone dimers (e.g. elgnica dimer A and elgnica dimer B), glycoproteins (e.g. aloctin A), fatty acids (e.g. β-sitosterol, cholesterol, campesterol), polysaccharides (e.g. acemannan, neutral and acidic polysaccharides (consisted of glucose, galactose, mannose, glucuronic acid or uronic acid)) and prostaglandins. [10][14][15][16]

A. vera at various developmental stages possessed minerals with different concentrations (e.g. sodium, magnesium, calcium, potassium, phosphorus). [15]

Plant Part Used

Leaves, gel. [17]

Traditional Use

A. vera has been traditionally used for burn healing but clinical evidence remains unclear. Mucilaginous tissue or A. veragel is located in the center of the A. vera leaf and have been used as cosmetics as well as medical products. A. vera gel has been used for many indications since the Roman era or even long before [17]. A. vera has been traditionally used as a topical treatment for burns, wounds, and various other skin conditions, and has also been used orally as a laxative [18].

The production of A. vera juice involves crushing, grinding or pressing of the entire leaf of the aloe vera plant followed by various steps of filtration and stabilization of the juice. Then, the A. vera juice incorporated in or mixed with other solutions or agents to produce the pharmaceutical, cosmetic or food product. [19]

The amount of A. vera that in the pharmaceutical industry is not negligible as far as the manufacturing of topical ointments, gel preparations, tablets and capsules are concerned [19]. In the cosmetic, A. vera gel find its application primarily acted as skin healer and prevents injury of epithelial tissues, cures acne and gives a youthful glow to skin and also acts as extremely powerful laxative [20]. Some toiletry industries has been made by A. vera, where it is used as a base for the preparation of creams, lotions, soaps, shampoos and facial cleaners. In the food industry, A. vera has been utilised as a resource of functional food, especially for the preparation of health food drinks and other beverages, including tea [19].

Preclinical Data

Pharmacology

Burn and wound healing activity

A. vera gel administered to full-thickness burns by direct contact with a hot plate Hartley guinea pigs significantly (p<0.02) showed a complete healing after average 30 days of treatment, which was faster compared to control group (50 days). [21]

A. vera geladministered to second-degree burns in guinea pigs hindered the wound healing process by significantly (p<0.01) thicken the granulation tissue with a significant (p<0.001) decreased in amount of hair follicles compared to 1% silver sulfadiazine cream. [22]

A. vera mature leaves gel administered to burn-created skin to Large White juvenile pigs (25-32 kg) for a duration of 6 weeks showed evaporative cooling capacities by decreasing the subdermal temperature within the burn skin of pigs due to its analgesic properties. [23]

Lyophilized A. vera powder of mature leaves gel (30 mg) administered orally and topically twice a day to excision wound-induced to male Wistar rats (150-200 g) for a duration of 8 days increased the collagen content of the granulation tissue and its crosslinking degree evidenced by the improved aldehyde content and reduced acid solubility observed compared to untreated control. [24]

Lyophilized A. vera powder of mature leaves gel (30 mg) administered orally and topically twice a day to excision wound-induced to male Wistar rats (150-200 g) for a duration of 16 days showed a wound healing properties by positively influenced the synthesis of glycosaminoglycan (GAG) components of the wound matrix with the elevated amount of ground substance synthesized and levels of reported glycohydrolases (hyaluronic acid and dermatan sulfate) compared to untreated control. [25]

Lyophilized A. vera gel administered to second degree burn wound-induced in male Wistar rats for a duration 14 days showed a better healing area compared to untreated and normal saline treated group. The gel significantly (p<0.05) reduced the vasodilation, increased the postcapillary venular permeability as encountered in the untreated burn, increased the arteriolar diameter up to normal condition, reduced the amount of leukocyte adhesion as observed and showed that the postcapillary venular permeability was not different from the sham controls. [26]

Mannose-6-phosphate sugar of A. vera gel (300 mg/kg) administered by subcutaneous injections daily to wound-induced adult male ICR mice (30 g) for a duration of 7 days significantly (p<0.01) decreased the wound diameter about 4.3 mm (50.7 %) compared to saline treated control group with 2.8 mm (42.1 %). [27]

Anti-inflammatory activity

Mannose-6-phosphate sugar of A. vera gel (300 mg/kg) administered by subcutaneous injections daily to adult male ICR mice (30 g) for a duration of 7 days before the ear swelling croton oil assay to induce inflammation for 6 hours significantly (p=0.05) showed the lower average ear weight (5.5 mg) compared to saline treated control group (7.3 mg). [27]

Aqueous and chloroform extract of A. vera fresh leaves gel (100 mg/kg) administered intraperitoneally to carrageenan-induced edema in paw of male Wistar rats (180-200 g) for a duration of 4 hours before an hour of carrageenan injection decreased the paw volumes from 160 µL to 75 and 62 µL, respectively comparable to standard indomethacin and dexamethasone. [28]

Aloctin A isolated from A. vera (5.0 mg/kg) administered intraperitoneally to arthritic-induced female Sprague-Dawley rats (±200 g) for a duration of 15 days inhibited the swelling in the injected foot and in the secondary lesion (day 14: 57.2 %; day 21: 56.6 % and day 14: 43.4 %; day 21: 72.3 % inhibition ratio, respectively) compared to gastric gavage administration of 2.0 mg/kg indomethacin (day 14: 38.1 %; day 21: 23.9 % and day 14: 12.1 %; day 21: -1.2 % inhibition ratio, respectively ) and 2.0 mg/kg prednisolone (day 14: 58.3 %; day 21: 43.2 % and day 14: 82.2 %; day 21: 35.7 % inhibition ratio, respectively). [29]

Aloctin A isolated from A. vera (10.0 mg/kg) administered intraperitoneally to carrageenan-induced edema in paw female Sprague-Dawley rats (±200 g) for a duration of 5 hours suppressed the swelling in the rat hind paw (95.3 % inhibition ratio) compared to gastric gavage administration of 2.0 mg/kg indomethacin (59.0 % inhibition ratio) in dose-dependent manner. [29]

C-glucosyl chromone identified as 8-[C-β-D-[2-O-(E)-cinnamoyl]glucopyranosyl]-2-[(R)-2-hydroxypropyl]-7-methoxy-5-methylchromone from ethanol extract of A. vera leaves (200 µg/mouse ear) administered to croton oil-induced ear swelling in male BalbC mice (20-25 g) for a duration of 6 hours showed anti-inflammatory activity with no reduction in thymus weight comparable to administration of 200 µg/mouse ear hydrocortisone but with 50 % thymus weight decrement. [30]

A. vera administered orally to several reagents (kaolin carrageenan, albumin, dextran, gelatin, and mustard) induced-hind paw rats showed remarkable anti-inflammatory activity especially in gelatin-induced and kaolin-induced edema and showed lowest activity for dextran-induced edema, dependent on the presence of anthraquinones in the extract. [31]

A. vera and its compound namely gibberellin (2-100 mg/kg) administered to streptozotocin-induced diabetic mice inhibited the polymorphonuclear leukocyte infiltration into the site, thus provided anti-inflammatory activity in a dose dependant manner. [32] 

Antiallergic activity

Alprogen of glycoproteins compound isolated from A. vera fresh leaves showed antiallergic activity by significantly (p<0.001) inhibited the mediator releases (histamine and leukotriene) and Ca2+ influx caused by activation of mast cells (0.1 µg/mL ovalbumin) by specific antigen-antibody reactions in vitro of Hartley albino female guinea pigs (200-250 g) lung. The extract reduced the amount of hispidine and leukotrienes (7.5±7.50 % and 23.2±6.23 pmol/4x105 cells,respectively) compared to control (29.0±1.10 % and 42.9±5.40 pmol/4x105 cells, respectively). [33]

Antihyperglycemic activity

A. vera of fresh leaves gel and its isolated phytosterols (lophenol, 24-methyl-lophenol, 24-ethyl-lophenol, cycloartanol, and 24-methylene-cycloartanol) (1 µg/mL) was administered orally to type 2 diabetic BKS.Cg-m+/+Leprdb/J (db/db) mice. The extracts significantly decreased (15-18 %) the hemoglobin A1c (HbA1c) levels in mice compared to vehicle (saline)-treated mice after 35 days and reduced blood glucose levels to approximately 64%, 28%, 47%, 51%, and 55% of control levels, respectively for a duration of 28 days treatment. [34]

A. vera dried sap (500 mg/kg) administered orally twice daily for duration of 7 days significantly (p<0.01) lowered the glucose blood levels in alloxan-induced diabetic of Swiss albino mice (394 ± 22.0 mg/dl) compared to glibenclamide (726 ± 30.9 mg/dl) and control mice (646 ± 35.9 mg/dl). [35]

Bitter principle of A. vera leaves (5 mg/kg) administered intraperitoneally to alloxan-induced diabetic of Swiss albino mice for duration of 24 hours highly significant lowered the glucose blood levels compared to oral administration of A. vera extract. Bitter principle of A. vera leaves and A. vera extract administered once a day and twice daily, respectively for chronic studies for a duration of 4 days showed the maximum blood glucose level reduction at the 5th day. The reduction was suggested due to stimulation synthesis and/or release of insulin from the beta cells of the Islets of Langerhans. [36]

A. vera leaves pulp extract (500 mg/kg) administered orally to streptozotocin (STZ)-induced type I diabetic female Wistar rats (150-200 g) for a duration of 6 hours and STZ-induced type II diabetic Wistar pups for a duration of 5 hours showed antihyperglycaemic activity in both but effectively enhanced in type II compared to glibenclamide. Contrarily, the A. vera leaves gel extract (10 mL/kg) administered orally to the rats had a hyperglycemic effect in the type II diabetic rats [37].

Antitumour activity

Aloe-emodin (AE), a hydroxyanthraquinone constituent of A. vera leaves inhibited the growth of human neuroectodermal tumors in mice through the induction of apoptosis, where the selectivity against neuroectodermal tumor cells was founded on a specific energy-dependent pathway of drug incorporation. [38]

Antiulcerative activity

Aloe-emodin of A. vera showed the growth inhibition of H. pylori collected from peptic ulcer patients in vitro by inhibited its Arylamine N-acetyltransferase (NAT) activities. [39]

A. vera leaves gel also reported to has antiulcer activity in rats with peptic ulcer disease. [40]

Antioxidant activity

Lyophilized of whole A. vera fresh leaves extract (2, 3, and 4-year-old plants) showed different content of flavonoids for different growth stages A. veta. The 3-year-old extract (100mg/L) exhibited the fastest DPPH radical scavenging rate of activity over the first 16 and 30 minutes (67.95±0.99 % and 72.19±0.98 % inhibition, respectively) compared to BHT, α-tocopherol, 4-year-old and 2-year-old growth stages of A. vera (64.60±1.12 %, 64.20±1.55 %, 56.85±3.42 %, 51.92±0.45 % and 70.52±0.89 %, 65.20±1.32 %, 67.64±2.99 %, 62.70±0.44 % inhibition, respectively). [41]

Antimicrobial activity

Antifungal activity

Aqueous ethanol extract of A. vera fresh leaves showed significant (P<0.001) antifungal activity based on fungicidal concentration against fungus growth of Botrytis gladiolorum (MFC 80 µL/mL), Fusarium oxysporum f.sp. gladioli (MFC 100 µL/mL), Heterosporium pruneti (MFC 100 µL/mL) and Penicillium gladioli (MFC 100 µL/mL)compared to control (70% aqueous ethanol) and standard antimycotic drug (Diflazon).[42]

Ethanol extract of A. vera dry leaves showed antifungal activity against Aspergillus niger, Cladosporium herbarum, and Fusarium moniliforme (at 5 mg/mL) for a duration of 48 hours incubation at 28oC using disc plate method with 14 mm, 18 mm, and 33.7 mm inhibition, respectively. Compound F isolated from ethanol extract and compound I from aqueous extract of A. vera showed MIC value of 125 µL/mL and 250 µL/mL, respectively. [43]

Antivirus activity

A combination of acemannan (ACE-M) extracted from A. vera with suboptimal noncytotoxic concentrations of azidothymidine (AZT) synergistically acted to inhibit the replication of HIV-1 or with acyclovir (ACY) to inhibit herpes simplex virus type 1 (HSV-1). [44]  

Purified extracts of A. vera leaves gel namely R1 (from immature leaves harvested in the early summer), S1 (from mature leaves harvested in the autumn), and F2 (from ethanol extract of freeze mature leaves harvested in the autumn) at concentration of 10-1 dilution showed substantial antiviral activity against human cytomegalovirus using plaque inhibition test. [45]

Laxative activity

Barbaloin constituent of A. vera (31.1 mg/kg) administered intracecally for a duration of 4 hours showed a cathartic effect by increase the water content and stimulated mucus secretion caused by the existence of aloe-emodin-9-anthrone(AE-anthrone) (568 µg/rat) from barbaloin in the rat large intestine. [46]

Toxicity

No documentation.

Clinical Data

Clinical findings

Herbal therapies in general and A. vera in particular, are already widely used by patients with inflammatory bowel disease [47][48]. Previous clinical trials of varying design and accessibility have claimed that Boswellia serrata and several traditional Chinese medical approaches are beneficial in active ulcerative colitis. In this randomized, double-blind, placebo-controlled clinical trial, treatment for 4 weeks with oral A. vera gel produced a symptomatic clinical response more frequently than did placebo [47]. A. vera gel may decrease the production of stomach acid and also block the growth of Helicobacter pylori, a bacterium that causes stomach ulcers [48]. However, statistically significant clinical studies on the efficacy of A. vera gel on human health are very limited and often inconclusive [49].

Reported clinical trials

Wound healing

One non-randomised, unblinded study assessed wound healing with polyethylene oxide wound gel or polyethylene oxide wound gel saturated with A. vera in 17 patients with acne vulgaris. Half-face treatments were carried out so that each patient received both treatments. By day 5, 90% of wounds were healed (complete re-epithelialisation) with A. vera compared with 40-50% without A. vera. Wound healing was 72 hours faster with A. vera. It is significant to reduce bacterial contamination, subsequent keloid formation, and/or pigmentary changes. [50]

One randomised, unblinded trial assessed wound healing with standard wound care with or without  A. vera dermal gel every 8-12 hours in 40 women after gynaecological surgery. All women had complications of wound healing after surgery. Details of the standard treatment were not provided and 50% of the women did not complete the trial. Mean healing time (to completely epithelised wound) was significantly longer with A. vera (83 days) than with standard treatment (53 days). [51]

A single small trial of A. vera supplementation versus gauze suggests delayed healing with A. vera, the results of this trial are uninterpretable since there was a large differential loss to follow up. A plaster cast applied to an amputation stump accelerated wound healing compared with elastic compression. This clinical trial reported that there were no statistically significant differences in healing for other dressing comparisons (e.g. gauze, foam, and alginate). [52]

Burned skin

A systematic review was conducted to determine the efficacy of topical A. vera for the treatment of burn wounds. 4 controlled clinical trials for burn healing with a total of 371 patients were included. Two reviewers independently extracted data on study characteristics, patient characteristics, intervention, and outcome measure. In first and second degree burns, the healing process of burnt wound as well as post-skin grafting might be effective using A. vera since it increases the rate of epithelialisation when compared with conventional treatments. [17]

While scientific research is slow to acknowledge the fact that A. vera gel is very soothing to burned skin and does promote healing, it has been reported to be effective in treating various types of burns depending on the severity of the burn [17][53]. In a reported clinical study, 27 patients with partial thickness burn wound were treated with A. vera gel compared with vaseline gauze. This study revealed the effectiveness of A. vera gel in treating lesion when it healed faster than the vaseline gauze area. According to these 27 cases, only some minor adverse effects, such as discomfort and pain were encountered [53].

Aloe may also provide benefit to the skin burns that result from radiation therapy. A blinded clinical trial evaluated the prophylactic use of a mild soap alone compared to the use of A. vera gel together with the mild soap. Lower cumulative doses of radiation showed no difference existed in the effect of adding aloe. In patients receiving higher cumulative radiation doses, the median time for skin changes were observed in 3 weeks for the patients treated with mild soap only, while 5 weeks for the patients treated with both mild soap and aloe gel. When the cumulative dose increases over time, there seems to be a protective effect of adding aloe to the soap regimen. [54]

Psoriasis vulgaris

Evidence from one human trial suggests that 0.5% extract from A. vera in a hydrophilic cream is an effective skin treatment and may improve symptoms of certain skin conditions such as psoriasis vulgaris. One randomised, double-blind trial assessed a topical 0.5% hydrophilic A. vera cream compared with placebo cream in 60 patients with mild to moderate chronic plaque-type psoriasis over four weeks. Patients were followed-up for 12 months. The effect of a commercial A. vera gel on stable plaque psoriasis was modest. The rate of cure was significantly better with A. vera (83%) than with placebo (7%) with no relapses. [55]

Radiation-induced skin injury

Two randomised trials assessed the effects of A. vera in women with radiation-induced skin injury associated with treatment for breast cancer. One trial was double-blind (194 patients) and was found no significant difference in severity score between topical A. vera gel and placebo gel. [56]

The other trial (108 patients) assessed usual care with or without topical A. vera gel; there was no significant difference between study treatments. [56]

Reports in the 1930s of topical aloe's beneficial effects on skin after radiation exposure lead to widespread use in skin products. Currently, aloe gel is sometimes recommended for radiation-induced dermatitis, although scientific evidence suggests a lack of benefit in this area [57]. In addition data on atopic dermatitis and chronic venous insufficiency treated with A. vera gel and tea tree oil also indicated that there is no compelling evidence for their effectiveness as reviewed from the various clinical studies [58].

Genital herpes

Preliminary evidence suggests that A. vera gel may improve symptoms of genital herpes. Two randomised, double-blind trials compared topical A. vera cream (0.5% hydrophilic) or placebo three times daily for two weeks in 180 men with a first episode of genital herpes; one also assessed topical A. vera gel. Response rates in the two trials were almost identical. The proportions of patients cured in the two trials were 70% and 67% with Aloe vera cream, 45% with A. vera gel, and 7.5% and 7.0% with placebo. A. vera cream healing times were 4.8 and 4.9 day, 7.0 days with A. vera gel, and 14 and 12 days with placebo. Limited evidence from human studies suggests that 0.5% extract from A. vera in a hydrophilic cream may be an effective treatment of genital herpes in men (better than aloe gel or placebo). [59]

Diabetes mellitus

A review of a total of 108 trials examining 36 herbs and 9 vitamin/mineral supplements including 58 controlled clinical trials (42 randomised and 16 non-randomized trials) involving 4565 patients with diabetes or impaired glucose tolerance revealed that A. vera is one of the most promising herbs for antidiabetic. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). The plant has positive preliminary results with very few adverse effects reported as generally safe. [60]

A. vera is also has been recognised among 45 plants and their products (active, natural principles and crude extracts) that have been used in the Indian traditional system of medicine to have shown experimental or clinical evidence of antidiabetic activity. [61]

Constipation

In a study of 35 men and women with constipation, those who received capsules containing aloe latex, and other laxatives including psyllium (a natural substance high in fiber) experienced softer and more frequent stools compared to those who received placebo. [62]

Hypoglycemic effect

Preliminary studies suggest that aloe latex may help lower blood sugar levels (hypoglycemic effect) in people with type 2 diabetes (adult onset diabetes) [35][60]. Although further studies are need to fully assess the safety and effectiveness of aloe in the treatment of diabetes, it seems possible that the herb may prove to be a useful addition to the diet, exercise, and medication program for type 2 diabetics [60].

HIV infection

Acemannan, a component of A. vera, has been shown in laboratory tests to have immune-stimulating and anti-viral activities. Double-blind placebo-controlled pilot trial of acemannan involved 63 patients (all were males (mean age 39 years). 6 patients in the acemannan group and 5 in the placebo group developed AIDS-defining illnesses. 24 patients, 11 receiving placebo and 13 receiving acemannan  discontinued study therapy prematurely, none due to serious adverse reactions. Results from early human studies are mixed, and due to weaknesses in the way these studies were designed, firm conclusions are not possible. Without further human trials, the evidence cannot be considered convincing either in favour or against this use of aloe. [63]

Mucositis (mouth sore)

There is preliminary evidence from a human trial that oral A. vera does not prevent mucositis (mouth sores) associated with radiation therapy. Oral A. vera also did not improve tolerance to head-and-neck radiotherapy, reduce soreness, or improve patient well-being. This clinical study had been conducted among 58 patients with head-and-neck cancer. [64]

Immunostimulant activity

Enhancement of macrophage activity, T-cell function, and interferon production by the body was reported with use of this agent. Acemannan has been anecdotally reported to be a potential therapeutic agent in the treatment of HIV and herpes simplex type 1, yet supportive evidence is lacking at this time. [63]

Ulcer

A study of randomized patients to receive either daily topical application of the hydrogel study dressing (acemannan hydrogel wound dressing) or a moist saline gauze dressing was conducted. Results show complete healing of the study ulcer occurred in 19 of 30 subjects during the 10-week observation period. An amorphous hydrogel dressing derived from the A. vera containing acemannan is approved by the Food and Drug Administration (FDA) for the management of stages I through IV pressure ulcers. The effectiveness of Acemannan hydrogel dressing is almost like moist saline gauze wound dressing for the management of pressure ulcers. [65]

A new bioadhesive patch of A. vera hydrogel, tried for aphthous stomatitis, was found effective in more than 80% of cases with 90% compliance in adhesivity, acceptability and palatability of the formulation. [66]

Acne vulgaris

84 subjects presenting with clinically significant Acne vulgaris were randomly assigned with different test preparations (aloe gel, placebo or control preparations). In combination with Ocimum oil, the effect by A. vera on the anti-acne properties induced synergistic effect which is more effective than the drug 1% Clindamycin in the treatment of Acne vulgaris. [67]

Precautions

Diabetes mellitus

Some research suggests aloe might lower blood sugar. If you take aloe by mouth and you have diabetes, monitor your blood sugar levels closely. [68]

Intestinal conditions such as Crohn's disease, ulcerative colitis, or obstruction

Do not take aloe latex if you have any of these conditions. Aloe latex is a bowel irritant. Remember, products made from whole aloe leaves will contain some aloe latex. [48][68]

Haemorrhoids

Do not take aloe latex if you have haemorrhoids. It could make the condition worse. Remember, products made from whole aloe leaves will contain some aloe latex. [48][68]

Kidney problems

High doses of aloe latex for prolonged amounts of time have been attributed to kidney failure, some deaths and other serious conditions. [48][68]

Surgery

Aloe might affect blood sugar levels and could interfere with blood sugar control during and after surgery. Stop taking aloe at least 2 weeks before a scheduled surgery. [68]

Allergic responses

Aloe belongs to the lily family of plants, which includes garlic and onions as well as flowers such as crocus, hyacinth, lilies, and tulips. Individuals who are allergic to other members of the lily family may also be sensitive to aloe. For susceptible individuals, touching aloe plants, applying aloe gel, or taking aloe juice supplements may result in allergic responses such as upset stomach or skin rash. [48]

Dermatitis

Skin products used to treat radiation dermatitis vary among institutions. Nurses should be aware that some patients may be predisposed to skin problems. Newly developed products based on A. vera need to take into account. These products should undergo some research or clinical trials so that effective treatment can be instituted. [54]

Side effects

A. vera gel might cause dermatological side effects such as burning red, rashes and itching of the skin [48][49][68]. Some cases of contact dermatitis may have been caused by handling aloe plants or applying aloe gel [48]. Discontinuing topical use is suggested if rash or irritation develops [69].

There have been a few reports of liver problems in some people who have taken an aloe leaf extract; however, this is uncommon. It is thought to only occur in people who are extra sensitive (hypersensitive) to aloe. [68]

Aloe latex can cause some side effects such as stomach pain and cramps. Long-term use of large amounts of aloe latex might cause diarrhoea, nausea, kidney problems, and blood in the urine, low potassium, muscle weakness, weight loss, and heart disturbances. Taking aloe latex 1 gram per day for several days can be fatal [48][68]. The oral use of aloe gel is inadvisable for individuals with any esophageal, stomach, or bowel disease due to the possibility that aloe gel may be contaminated with aloe latex. Individuals who have haemorrhoids should not take aloe latex due to the possibility that its use may worsen the condition [48].

Pregnancy/Breast Feeding

A possible presence of oestrogenic compounds in the aqueous extracts from the aloe leaves are used to regulate the menstrual cycle and to treat dysmenorrhea or infertility in women [70]. However, it is recommended that aloe latex should not to be used by pregnant or nursing women without supervision of a healthcare professional [71]. Although topical use of aloe is unlikely to be harmful during pregnancy or breastfeeding, oral use is not recommended due to theoretical stimulation of uterine contractions which may associated with miscarriage [48]. It could also be a risk for birth defects [68]. Women who are breast-feeding should also avoid taking/consuming aloe latex. Potentially harmful chemicals/active ingredients from aloe latex may pass from the mother to the baby in breast milk. The baby may develop diarrhoea [48].

Age limitation

Do not use in children under 2 years of age unless recommended by a physician. Babies and young children may be more likely to have reactions to chemicals in aloe latex [48]. Children at the range ages of 12-18 years old may experience abdominal pain, cramps and diarrhoea [48][68]. Caution is advised in patients with diabetes or hypoglycemia or kidney disease.

Adverse reaction

A. vera does not cause adverse dermal toxicity [72]. However, some patients may experience burning after topical application. The use of aloe on surgical wounds has been reported to slow healing and, in one case, to cause redness and burning (severe dermatitis) when A. vera was applied to the face after a skin-peeling procedure (dermabrasion). Patients undergoing dermabrasion or chemical peel procedures should be cautioned specifically against the use of A. vera topically in the first weeks after surgery. Application of aloe prior to sun exposure may lead to rash in sun-exposed areas [73].

The use of aloe or aloe latex by mouth for laxative effects can cause cramping or diarrhoea. Use for over seven days may cause dependency or worsening of constipation after the aloe is stopped [62]. There is a report of hepatitis (liver inflammation) with the use of oral aloe. From the study, improvement and resolution of liver damage following the rapid discontinuation of A. vera provide strong evidence that the A. vera preparation has caused the acute hepatitis [74].

Electrolyte imbalances in the blood, including low potassium levels, may be caused by the laxative effect of aloe. This effect may be greater in people with diabetes or kidney disease. Low potassium levels can lead to abnormal heart rhythms or muscle weakness. People with heart disease, kidney disease, or electrolyte abnormalities should not take aloe by mouth. Healthcare professionals should monitor for changes in potassium and other electrolytes in individuals who take aloe by mouth for more than a few days. [75]

Interaction & Depletion

Interaction with drug

Medications for diabetes (Antidiabetes drugs)

There is a scientific rationale for the use of A. vera as an antidiabetic agent [76]. Taking aloe gel along with diabetes medications might cause the blood sugar to go too low. People with diabetes who use aloe latex either alone or in combination with other medications must be monitored closely by health care providers to avoid potential complications from low blood sugar levels followed by the changes intake of dose diabetes medication [68]. Some medications used for diabetes include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), metformin, tolazamide, acarbose, acetohexamide, miglitol, repaglinide and nateglinide [36][68].

Medications taken by mouth (Oral drugs)

When taken by mouth, aloe latex which is a strong laxative will promotes the production of mucus and causes spasms in the lower gastrointestinal (GI) tract by irritating the inside layer of the large intestines and colon [48]. Laxatives can decrease how much medicine absorbed by the body. Taking aloe latex along with medications (orally) might decrease the effectiveness of your medication [68]. So that, the oral use of aloe latex is not recommended. In 2002, the U.S. Food and Drug Administration (FDA) required manufacturers of aloe-containing laxative products to remove those products from the market because no credible evidence showed aloe laxatives to be either safe or effective to use [48].

Sevoflurane (Ultane)

Aloe appeared to interact with the general anesthetic sevoflurane [77]. Aloe might decrease clotting of the blood. Sevoflurane is used as anesthesia during surgery. Sevoflurane also decreases clotting of the blood. Taking aloe before surgery might cause increased bleeding during the surgical procedure. Do not take aloe orally if the patients are having surgery within 2 weeks [68].

Stimulant laxatives

When taken orally aloe latex is a type of laxative called a stimulant laxative. Stimulant laxatives speed up the bowels. Taking aloe latex along with other stimulant laxatives could speed up the bowels too much and cause dehydration and low minerals in the body. Some stimulant laxatives include bisacodyl (Correctol, Dulcolax), cascara, castor oil (Purge), senna (Senokot), and others. [68]

Warfarin (Coumadin)

When taken orally, aloe latex is a type of laxative called a stimulant laxative. Stimulant laxatives speed up the bowels and can cause diarrhoea in some people. Diarrhoea can increase the effects of warfarin and increase the risk of bleeding. Do not take excessive amounts of aloe latex together with warfarin. [68]

Digoxin (Lanoxin)

When taken by mouth aloe latex is a type of laxative called a stimulant laxative. Stimulant laxatives can decrease potassium levels in the body. Instead of increasing the risk of side effects of digoxin (Lanoxin) [68], combination of these two medications will lowering the potassium levels, thus resulting in muscle weakness and potentially dangerous changes in heart rhythm. Digoxin side effects may include changes in vision, drowsiness, heart rhythm changes, nausea, and vomiting [48].

Water pills (Diuretic drugs)

"Water pills" can also decrease potassium in the body. Taking aloe latex along with "water pills" might decrease potassium in the body too much. Some "water pills" that can decrease potassium include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), hydrochlorothiazide (HCTZ, Hydrodiuril, Microzide), and others. [68]

Corticosteroid

Both corticosteroid drugs and aloe latex may promote the loss of potassium from the body. It is best not to take aloe latex and corticosteroids at the same time. Corticosteroids are used for a wide range of inflammatory conditions including arthritis, asthma, cancer, eye conditions, and skin infections. Commonly prescribed corticosteroids include beclomethasone (Beconase, Beclovent, Vancenase, Vanceril), dexamethasone (Decadron), hydrocortisone, methylprednisolone (Medrol), prednisolone, prednisone (Deltasone, Orasone) and triamcinolone (Azmacort, Nasacort) [48]. Aloe gel may enhance the ability of hydrocortisone to reduce swelling [78].

Zidovudine (ZDV) or didanosine (ddI)

Acemannan was well tolerated and showed no significant pharmacokinetic interaction with zidovudine (ZDV). Zidovudine was given to antiretroviral therapy among patients with advanced HIV disease together with acamannan (400 mg orally four times daily) [63]. Zidovudine does not cure HIV or AIDS, but combinations of drugs that treat HIV infection may slow progress of the disease development.

Interaction with other Herbs

If aloe latex is taken at the same time as other herbs that also affect the heart, potentially dangerous changes in heart function may result. Some herbal products with heart effects are European Mistletoe, Ginger (in large doses, Hawthorn, Motherwort, Panax Ginseng, Pleurisy Root and Squill. Aloe latex possibly could increase the laxative effects of other herbal laxatives including Alder Buckthorn, Cascara, Castor Oil, Rhubarb, Senna and Yellow Dock. Both aloe latex and extremely large amounts of true licorice (not licorice flavoring) can promote the loss of potassium from the body, potentially causing muscle weakness and changes in heart rhythm. Low levels of potassium (due to oral aloe) could interfere with cardiac glycosides as well as affect other antiarrhythmic agents. Potassium deficiency can be exacerbated by simultaneous applications of thiazide diuretics, cortico-adrenal steroids or licorice root [79]. The amounts of licorice ordinarily consumed as candy are not thought to be large enough to present a problem. Some interactions between herbal products and medications can be more severe than others. It is recommended to tell the doctor or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals to avoid harmful interaction [48].

Contraindications

People with known allergy to garlic, onions, tulips, or other plants of the Liliaceae family may have allergic reactions to aloe [48]. A. vera is contraindicated (in individuals with) hemorrhoids, heart conditions, and kidney disorders. Likely unsafe for use during pregnancy because aloe can induce abortions and stimulate menstruation. A. vera is contraindicated when menstruating, due to possible stimulation of endometrial activity [61]. Aloe latex should not be taken internally if the following drugs are also taken: digoxin (Lanoxin), diuretics, steroids, drugs for irregular heartbeat and drugs that cause potassium loss [80].

Some studies reported positive results while others showed adverse effects in the patients taking A. vera gel and placebos [50][52]. Of the 30 patients randomized to A. vera gel, one complained of abdominal bloating, one of pain in her feet, one of sore throat, one of transient ankle swelling, one of acne and one of worsening eczema. Of the 14 patients taking placebo, two reported bloating, one foot pain and one acne problem. No patients developed abnormal blood tests attributable to A. vera gel or placebo, or were withdrawn from the trial because of adverse effects [47].

Case Report

A. vera leaf gel has been used for centuries as a topical wound healing agent for traumatic wounds (from mechanical, traumatic, or thermal injury, including contusions, abrasions, punctures, fractures, sunburn and burns), and chronic wounds (including pressure and diabetic ulcers) [47]. Although previous studies failed to support the use of aloe in diabetes, several recent animal studies have shown that both aloe gel and aloe latex may help to lower blood sugar levels [48]. The results from a small study investigated taking A. vera orally and its effects on ulcerative colitis showed that after 4 weeks, aloe produced clinical effects greater than placebo although more studies are needed [47]. Another case has reported that 35% of patients with Irritable Bowel Syndrome showed response to the treatment of A. vera compared to placebo group of 22% showing treatment in one month duration [81].

In another case reports and a few small studies, application of A. vera gel was helped to lessen or prevent damage caused by frostbite for individuals and animals exposed to extremely cold temperatures. It is believed that chemicals in A. vera gel may keep small blood vessels in the fingers and toes from shrinking, thereby preventing the surrounding tissues from freezing [48].

A 39-year-old liver transplant patient who took a laxative containing aloe for ten months has developed melanosis coli. One year after stopping the anthranoid medication, the pigments disappeared but a polypoid lesion appeared in the transverse colon [82]. A 47-year-old South African, developed acute oliguric renal failure and liver dysfunction after ingestion of an herbal remedy, found by mass spectrometric and chromatographic analysis, to contain Cape aloes [83].

Dosage

Aloe is reported safe in recommended dosages. But, based on pharmacology, long term use or higher than recommended dosages may cause fluid and electrolyte imbalances [75]. As aloe is a laxative, products should not be taken long-term unless aloin and aloe-emodin free products are used. If used in wound healing and wound has not improved in five to seven days, seek further medical attention. Aloe gel is available in a number of topical products such as creams, gels, lotions, and ointments. It can also be obtained from an aloe houseplant, simply by breaking off one of the plants leaves [48].

The following doses have been studied in scientific research: 

Oral (by mouth) as an oral supplement

Constipation

The dose often recommended is the minimum amount to maintain a soft stool, typically 0.04-0.17 g of dried juice (corresponds to 10-30 mg hydroxyanthraquinones). As an alternative, in combination with celandin (300 mg) and psyllium (50 mg), 150 mg of the dried juice/day of aloe has been found effective as a laxative in research [62]. For daily intake, 100-200 mg aloe or 50mg aloe latex is recommended, particularly in the evening; however, it might not be safe to take aloe latex for this use [68].

Itchy rash on the skin or mouth (Lichen planus)

A. vera may be useful in lichen planus, a disease that involves the skin and mucous membranes characterized by unique eruptions. The cause of this disease is unknown, but has been linked to emotional stress, and has also been attributed to viral infections [84]. Research shows that using a mouthwash containing aloe 3 times daily for 12 weeks or applying a gel containing aloe twice daily for 8 weeks can reduce pain associated with itchy rashes in the mouth. Other research shows that using a mouthwash containing aloe 4 times daily for one month reduces pain and increases healing similarly to standard treatment in people with itchy rashes in the mouth [68].

Diabetes (type 2)

1 tablespoon of the aloe latex (5-15 mL) has been used twice daily [68]. However, safety and efficacy of this dose has not been proven.

HIV infection

Acemannan (1000-1600 mg) taken orally in four equal doses. A study demonstrated that acemannan at an oral daily dose of 1600 mg does not prevent the decline in CD4 cell count (white blood cells that play important roles in the immune system) characteristic of progressive HIV disease [63]. However, effectiveness and safety have not been proven by studies.

Ulcerative colitis

A. vera gel taken orally helped reduce symptoms of patients with ulcerative colitis due to its anti-inflammatory effect. [47]

Topical (applied to the skin)Adults (18 years and older)

Psoriasis vulgaris

Hydrophilic cream of 0.5% (by weight) of a 50% ethanol extract of aloe, combined with mineral and castor oils, applied 3 times daily aloe for five consecutive days per week for up to 4-8 weeks seems to reduce the skin plaques and decrease the severity of psoriasis. However, using an aloe gel does not seem to improve other symptoms associated with psoriasis, including skin redness [55][68].

Cold sores (herpes simplex virus [HSV-1])

Some evidence shows that applying an aloe extract 0.5% cream 3 times daily increases healing rates in men with cold sores [68].

Genital herpes (herpes simplex virus [HSV-2])

Hydrophilic cream of 0.5% (by weight) of a 50% ethanol extract, combined with liquid paraffin and castor oil, three times daily on lesions for five consecutive days per week, for up to two weeks has been studied. [59]

Minor burns

Some creams for minor burns have just 0.5% A. vera. [68]

Dosage Range

No documentation.

Standardisation

No documentation.

Poisonous Management

No documentation.

Line drawing

20

 

Figure 1: The line drawing of A. vera (L.) Burm. f. [2].

References

  1. The plant list. Ver 1.1. Aloe vera (L.) Burm f [homepage on the Internet]. c2013 [updated 2012 March 26; cited 2014 November 18]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-298116.
  2. Aguilar NO, Brink M. Aloe vera (L.) Burm f. In: de Padua L S, Bunyapraphatsara N, Lemmens RHMJ, editors. Plant Resources of South-East Asia No. 12(1): Medicinal and poisonous plants 1. Leiden, Netherlands: Backhuys Publisher, 1999; p. 104-105.
  3. Schmelzer GH. Plant resources of tropical Africa: Medicinal plants Vol. 1. Leiden, Netherlands: Backhyus publisher; 2008. p. 82.
  4. Kapoor LD. Handbooks of ayuverdic medicinal plants: Herbal reference library ed. Boca Raton: Florida: CRC press LLC; 2001. p. 28.
  5. Philippines Medicinal Plants.Sabila. Aloe vera Linn. [homepage on the Internet]. c2014 [updated 2014 Aug; cited 2014 Oct 14]. Available from: http://www.stuartxchange.com/Sabila.html
  6. Panda H. Aloe Vera Handbook Cultivation, Research Finding, Products, Formulations, Extraction & Processing. India: National Institute of Industrial Re; 2003.
  7. Prota4u. Aloe vera (L.) Burm.f. [homepage on the Internet]. No date [cited 2014 Nov 17]. Available from: http://www.prota4u.org/
  8. Sittichai N, Picheansoonthon C, editor. Herbal medicines used in primary health care in ASEAN. Nonthaburi, Thailand: Thai Traditional and Alternative Medicine; 2014. p. 79-80
  9. Wu XF, Wan JZ, Luo BJ, Yang MR, Ding WJ, Zhong JS. A novel naphthalene derivative from Aloe barbadensis. Yao Xue Xue Bao. 2013;48(5):723-7.
  10. Yang QY, Yao CS, Fang WS. A new triglucosylated naphthalene glycoside from Aloe vera L. Fitoterapia. 2010;81: 59-62.
  11. Zhong J, Huang Y, Ding W, Wu X, Wan J, Luo H. Chemical constituents of Aloe barbadensis Miller and their inhibitory effects on phosphodiesterase-4D2013. Fitoterapia. 2013;91:159-165.
  12. Wu X, Ding W, Zhong J, Wan J, Xie Z. Simultaneous qualitative and quantitative determination of phenolic compounds in Aloe barbadensis Mill by liquid chromatography–mass spectrometry-ion trap-time-of-flight and high performance liquid chromatography-diode array detector. J Pharm Biomed Anal. 2013;80:94-106.
  13. Pan X, Cao X, Dong Y, Zhao H. Preparative isolation and purification of cinnamoyl-C-glycoside chromone from aloe vera by high-speed countercurrent chromatography. Se Pu. 2005;23(1):96-9.
  14. McCarthy TJ, Mapp RK. A comparative investigation of methods used to estimate aloin and related compounds in Aloes. Planta Med. 1970;18(1):36-43.
  15. Ray A, Aswatha SM. An analysis of the influence of growth periods on physical appearance, and acemannan and elemental distribution of Aloe vera L. gel. Ind Crops Prod. 2013;48:36-42.
  16. Nejatzadeh-Barandozi F, Enferandi ST. FT-IR study of the polysaccharides isolated from the skin juice, gel juice, and flower of Aloe vera tissues affected by fertilizer treatment. Org Med Chem Lett. 2012;2(1):33-41.
  17. Maenthaisong R, Chaiyakunapruk N, Niruntraporn S, Kongkaew C. The efficacy of Aloe vera used for burn wound healing: A Systematic Review. J Burns. 2007; 33:713-718.
  18. Cassandra LQ. Plant Monograph Book. Georgia (USA): 2013; p. 12-22.
  19. Ramachandra CT, Srinivasa Rao P. Processing of Aloe vera leaf gel: A Review. Am J Agric Biol Sci. 2008; 3(2):502-510.
  20. Pankaj KS, Deen DG, Ritu S, et al. Therapeutic and Medicinal Uses of Aloe vera: A Review. J Pharmacol Pharm. 2013; 4:599-610.
  21. Rodriguez-Bigas M, Cruz NI, Suarez A. Comparative evaluation of Aloe vera in the management of burn wounds in guinea pigs. Plast Reconstr Surg. 1988;81(3):386-389.
  22. Kaufman T, Kalderon N, Ullmann Y, Berger J. Aloe vera gel hindered wound healing of experimental second-degree burns: A quantitative controlled study. J Burn Care Rehabil. 1988;9(2):156-159.
  23. Cuttle L, Kempf M, Kravchuk O, et al. The efficacy of Aloe vera, tea tree oil and saliva as first aid treatment for partial thickness burn injuries. Burns. 2008;34(8):1176-11782.
  24. Chithra P, Sajithlal GB, Chandrakasan G. Influence of Aloe vera on collagen characteristics in healing dermal wounds in rats. Mol Cell Biochem. 1998;181(1-2):71-76.
  25. Chithra P, Sajithlal GB, Chandrakasan G. Influence of Aloe vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats. J Ethnopharmacol. 1998;59(3):179-186.
  26. Somboonwong J, Thanamittramanee S, Jariyapongskul A, Patumraj S. Therapeutic effects of Aloe vera on cutaneous microcirculation and wound healing in second degree burn model in rats. J Med Assoc Thai. 2000;83(4):417-425.
  27. Davis RH, Donato JJ, Hartman GM, Haas RC. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiatr Med Assoc. 1994;84(2):77-81.
  28. Vazquez B, Avila G, Segura D, Escalante B. Antiinflammatory activity of extracts from Aloe vera gel. J Ethnopharmacol. 1996;55(1):69-75.
  29. Saito H, Ishiguro T, Imanishi K, Suzuki I. Pharmacological studies on a plant lectin aloctin A. II. Inhibitory effect of aloctin A on experimental models of inflammation in rats. Jpn J Pharmacol. 1982;32(1):139-142.
  30. Hutter JA, Salman M, Stavinoha WB, et al. Antiinflammatory C-glucosyl chromone from Aloe barbadensis. J Nat Prod. 1996;59(5):541-543.
  31. Davis RH, Leitner MG, Russo JM, Byrne ME. Anti-inflammatory activity of Aloe vera against a spectrum of irritants. J Am Podiatr Med Assoc. 1989;79(6):263-276.
  32. Davis RH, Maro NP. Aloe vera and gibberellin. Anti-inflammatory activity in diabetes. J Am Podiatr Med Assoc. 1989;79(1):24-26.
  33. Ro JY, Lee BC, Kim JY, et al. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast cells activated with specific antigen-antibody reactions. J Pharmacol Exp Ther. 2000;292(1):114-121.
  34. Tanaka M, Misawa E, Ito Y, et al. Identification of five phytosterols from Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull. 2006;29(7):1418-1422.
  35. Ghannam N, Kingston M, Al-Meshaal IA, Tariq M, Parman NS, Woodhouse N. The antidiabetic activity of aloes: preliminary clinical and experimental observations. Horm Res. 1986;24(4):288-294.
  36. Ajabnoor MA. Effect of aloes on blood glucose levels in normal and alloxan diabetic mice. J Ethnopharmacol. 1990;28(2):215-220.
  37. Okyar A, Can A, Akev N, Baktir G, Sutlupinar N. Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models. PhytotherRes. 2001;15(2):157-161.
  38. Pecere T, Gazzola MV, Mucignat C, et al. Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors. Cancer Res. 2000;60(11):2800-2804.
  39. Wang HH, Chung JG, Ho CC, Wu LT, Chang SH. Aloe-emodin effects on arylamine N-acetyltransferase activity in the bacterium Helicobacter pylori. Planta Med. 1998;64(2):176-8.
  40. Sotnikova EP. Therapeutic use of aloe in experimental stomach ulcers. Vrachebnoe delo. 1984(6):71-74.
  41. Hu Y, Xu J, Hu Q. Evaluation of antioxidant potential of aloe vera (Aloe barbadensis Miller) extracts. J Agric Food Chem. 2003;51(26):7788-7791.
  42. Rosca-Casian O, Parvu M, Vlase L, Tamas M. Antifungal activity of Aloe vera leaves. Fitoterapia. 2007;78(3):219-222.
  43. Ali MIA, Shalaby NMM, Elgamal MHA, Mousa ASM. Antifungal effects of different plant extracts and their major components of selected aloe species. Phytother Res. 1999;13(5):401-7.
  44. Kahlon JB, Kemp MC, Yawei N, Carpenter RH, Shannon WM, McAnalley BH. In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir. Mol Biother. 1991;3(4):214-23.
  45. Saoo K, Miki H, Ohmori M, Winters WD. Antiviral activity of aloe extracts against cytomegalovirus. Phytother Res. 1996;10(4):348-350.
  46. Ishii Y, Tanizawa H, Takino Y. Studies of aloe. V. Mechanism of cathartic effect. (4). Biol Pharm Bull. 1994;17(5):651-653.
  47. Langmead L, Feakins RM, Goldthorpe S, et al. Randomized, double‐blind, placebo‐controlled trial of oral Aloe vera gel for active ulcerative colitis. Aliment Pharmacol Ther. 2004;19(7):739-747.
  48. Let’s Drug. Application of Aloe vera. [homepage on the Internet]. c2014 [updated 2014; cited 2014 December 8]. Available from: http://www.letsdrug.com/meds/260/
  49. Sahu PK, Giri DD, Singh R, et al. Therapeutic and medicinal uses of Aloe vera: a review. Pharmacol Pharm. 2013;4(08):599.
  50. Fulton JE. The stimulation of postdermabrasion wound healing with stabilised Aloe vera gel-polyethylene oxide dressing. J Dermatol Surg Oncol. 1990;16(5):460-467.
  51. Schmidt JM, Greenspoon JS. Aloe vera dermal wound gel is associated with a delay in wound healing. Obstet Gynecol. 1991;78(1):115-117.
  52. Vermeulen H, Ubbink DT, Goossens A, de Vos R, Legemate DA, Westerbos SJ. Dressings and topical agents for surgical wounds healing by secondary intention. Cochrane Database Syst Rev. 2004(2):CD003554.
  53. Visuthikosol V, Chowchuen B, Sukwanarat Y, Sriurairatana S, Boonpucknavig V. Effect of Aloe vera gel to healing of burn wound a clinical and histologic study. J Med Assoc Thai. 1995;78(8):403-409
  54. Olsen DL, Raub JW, Bradley C, et al. The effect of Aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy. Oncol Nurs Forum. 2001;28(3):543-547.
  55. Syed TA, Ahmad SA, Holt AH, Ahmad SA., Ahmad SH, Afzal M. Management of psoriasis with Aloe vera extract in a hydrophilic cream: A placebo-controlled, double-blind study. Trop Med Int Health. 1996; 1(4): 505–509.
  56. Williams MS, Burk M, Loprinzi CL, et al. Phase III double-blind evaluation of an Aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. Int J Radiat Oncol Biol Phys. 1996;36(2):345-349.
  57. Richardson J, Smith JE, McIntyre M, Thomas R, Pilkington K. Aloe vera for preventing radiation-induced skin reactions: a systematic literature review. Clin Oncol (R Coll Radiol). 2005;17(6):478-484.
  58. Ernst E, Pittler MH, Stevinson C. Complementary/alternative medicine in dermatology: Evidence-assessed efficacy of two diseases and two treatments. Am J Clin Dermatol. 2002; 3(5): 341-348.
  59. Syed TA, Cheema KM, Ahmad SA, Holt Jr AH. Aloe vera extracts 0.5% in a hydrophilic cream versus Aloe vera gel for the management of genital herpes in males. A placebo-controlled, double-blind, comparative study. J Eur Acad Dermatol Venereol 1996; 7(3): 294-295. In: Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical effectiveness. Brit J Gen Pract. 1999; 49(447): 823-828.
  60. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003; 26(4): 1277-1294.
  61. Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol. 2002; 81(1): 81-100.
  62. Odes HS, Madar Z. A double-blind trial of a celandin, Aloe vera and psyllium laxative preparation in adult patients with constipation. Digestion. 1991; 49(2): 65-71.
  63. Montaner JS, Gill J, Singer J, et al. Double-blind placebo-controlled pilot trial of acemannan in advanced human immunodeficiency virus disease. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12(2): 153-157.
  64. Su CK, Mehta V, Ravikumar L, et al. Phase II double-blind randomized study comparing oral Aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms. Int J Radiat Oncol Biol Phys. 2004;60(1):171-177.
  65. Thomas DR, Goode PS, La Master K, Tennyson T. Acemannan hydrogel dressing versus saline dressing for pressure ulcers. A randomized, controlled trial. Adv Wound Care. 1998;11(6): 273-276.
  66. Andriani E, Bugli T, Aalders M, et al. The effectiveness and acceptance of a medical device for the treatment of aphthous stomatitis. Clinical observation in pediatric age. Minerva Pediatr. 1999; 52(1-2): 15-20.
  67. Orafidiya LO, Agbani EO, Oyedele AO, Babalola OO, Onayemi O, Aiyedun FF. The effect of Aloe vera gel on the anti-acne properties of the essential oil of Ocimum gratissimum Linn leaf – a preliminary clinical investigation. Int J Aromather. 2004; 14(1): 15-21.
  68. WebMD. Vitamin & Supplement. Aloe vera (Aloe vera (L.) Burm.f) [homepage on the Internet]. c2014 [updated 2014; cited 2014 December 18]. Available from: http://www.webmd.com/vitamins-supplements/ingredientmono-607-aloe.
  69. Ernst E. Adverse effects of herbal drugs in dermatology. Br J Dermatol. 2000; 143(5): 923-929.
  70. Telefo PB, Moundipa PF, Tchana AF, Tchouanguep DC, Mbiapo FT. Effects of an aqueous extract of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus, and Justicia insularis on some biochemical and physiological parameters of reproduction in immature female rat. J Ethnopharmacol. 1998; 63(3): 193-200.
  71. Barnes J. 2003. Pregnancy complementary therapies in pregnancy. Pharm J. 2003; 270(7241): 402-404.
  72. Moghbel A, Hematti A, Ghalambor A, Khorsgani ZN, Agheli H, Allipanah S. Wound healing and toxicity evaluation of Aloe vera cream. Toxicol Lett. 2007; 1(172): S233
  73. Hunter D, Frumkin A. Adverse reactions to vitamin E and Aloe vera preparations after dermabrasion and chemical peel. Cutis. 1991; 47(3): 193-196.
  74. Rabe C, Musch A, Schirmacher P, Kruis W, Hoffmann R. Acute hepatitis induced by an Aloe vera preparation: a case report. World J Gastroenterol. 2005; 11(2): 303-304.
  75. Ishii Y, Tanizawa H, Takino Y. Studies of aloe. III. Mechanism of cathartic effect (2). Chem Pharm Bull. Tokyo. 1990; 38(1): 197-200.
  76. Rajasekaran S, Ravi K, Sivagnanam K, Subramanian S. Beneficial effects of Aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes. Clin Exp Pharmacol Physiol. 2006; 33(3): 232–237.
  77. Lee A, Chui PT, Aun CS, Gin T, Lau AS. Possible interaction between sevoflurane and Aloe vera. Ann Pharmacother. 2004; 38(10): 1651-1654.
  78. Davis RH, Parker WL, Murdoch DP. Aloe vera as a biologically active vehicle for hydrocortisone acetate. J Am Podiatr Med Assoc. 1991; 81(1): 1-9.
  79. Mumoli N, Cei M. Licorice-induced hypokalemia. Int J Cardiol. 2008; 124(3): e42-e44.
  80. Shane-McWhorter L. Biological complementary therapies: a focus on botanical products in diabetes. Diabetes Spectr. 2001; 14(4): 199-208.
  81. Davis K, Philpott S, Kumar D, Mendall M. Randomised double-blind placebo-controlled trial of Aloe vera for irritable bowel syndrome. St Georges Hospital Medical School, London, UK. Int J Clin Pract. 2006; 60(9): 1080-1086.
  82. Willems M, van Buuren H, de Krijger R. Anthranoid self-medication causing rapid development of melanosis coli. Neth J Med. 2003; 61(1): 22-24.
  83. Luyckx VA, Ballantine R, Claeys M, et al. Herbal remedy-associated acute renal failure secondary to Cape aloes. Am J Kidney Dis. 2002; 39(3): 1-5.
  84. Hayes SM. Lichen planus--report of successful treatment with Aloe vera. Gen Dent. 1998; 47(3): 268-272.